19 - Chapter 14 Prescribing psychotropics 01 - Working towards adherence Working towards adherence 02 - What is adherence What is adherence? 03 - How common is non adherence How common is non-adherence? The Maudsley® Prescribing Guidelines in Psychiatry, Fifteenth Edition. David M. Taylor, Thomas R. E. Barnes and Allan H. Young. © 2025 David M. Taylor. Published 2025 by John Wiley & Sons Ltd. Chapter 14 Working towards adherence What is adherence? The first clear statement about adherence comes from Hippocrates (460–377 bc), who vividly described non-­adherence and linked it with poor outcomes. The World Health Organization (WHO) has described adherence as ‘the extent to which a person’s behaviour  – taking medication, following a diet, and/or executing lifestyle changes – corresponds with agreed recommendations from a healthcare provider’.1 In the UK, the National Institute for Health and Care Excellence (NICE) has, more succinctly, defined adherence as ‘the extent to which the patient’s action matches the agreed recommendations’.2 The more traditional notion of the patient ‘complying’ with the doctor’s orders seems patronising and to deny the agency of the patient.3 ‘Concordance’ is another term that has been used, which seems to refer to an agreement between the patient and the doctor. This is part of the notion of informed consent and is essential for a ‘prescribing partnership’ with patients.4 But, as we know, agreement about a course of action does not necessarily guarantee that the action will happen. Thus ‘adherence’ will be used in this section to refer to the development of behaviours that will, it is hoped, result in better outcomes for our patients. How common is non-­adherence? Large numbers of people, in most areas of medicine, do not seem to take their tablets very regularly – and so can be said to be partly or fully non-­adherent. This is a phenomenon that arises in other clinical areas as well, such as psychological therapies. For people referred to psychotherapy services in the north of England, 34% did not attend for their first assessment session and, of those who did, only 57% subsequently attended the first treatment session.5 Prescribing psychotropics 04 - Impact of non adherence Impact of non-adherence 928 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 14 For chronic physical and mental disorders, the picture is not much better. Although 76% of patients with several conditions reported adhering to medication, electronic monitoring suggested that, in fact, only 44% did so.6 Consistent with previous findings, a 2020 meta-­analysis suggested that, overall, about 50% of people with mental health problems do not take their medication as prescribed.7 This, however, may be an oversimplification. It is probable that a small proportion of patients are fully adherent, the majority are partially adherent to varying degrees, and a few never take any medication at all (of their own volition).8 These findings are not only characteristic of western medical culture, they are reflected in other parts of the world.9 Adherence rates also vary both over time and across settings. For example, 10 days after discharge from hospital, up to 25% of patients with schizophrenia are partially or completely non-­adherent with oral treatment and this figure rises to 50% at 1 year and to 75% by 2 years.10 Other studies have reported 25.8% complete discontinuation of medication within 1 year of discharge from hospital.11 In some mental healthcare settings, the rate of non-­adherence may be as high as 90%.12 Diagnosis may also be significant. An Austrian study found that significantly more patients with schizophrenia (66%) did not take their medication as prescribed, compared with patients with affective disorders (47%) or those with other psychiatric diagnoses (41%).13 A major issue is that poor adherence almost always occurs without the knowledge of the prescriber. In one study, prescribers identified only half of those who were non-­ adherent.14 In another, 35% of patients referred for treatment of (apparently) refractory schizophrenia had sub-­therapeutic plasma concentrations and many of them had plasma levels of zero.15 Impact of non-­adherence Medicines are only effective if taken at a therapeutic dose. And they are effective. A 20-­ year follow-­up study of 62 250 patients with schizophrenia reported a significantly lower suicide mortality during antipsychotic use compared with non-­use.16 Antipsychotic use also decreased overall mortality. Poor adherence to medication is a major risk factor for worse outcomes including relapse in people with schizophrenia,17–19 bipolar disorder20 and depression.21 Wider health benefits are also lost. Depressed patients who do not take an antidepressant have a 20% increased risk of an incident myocardial infarction compared with those who do.22 The serious consequences of non-­adherence with medication may be mitigated by implementing routine monitoring. Data were collected as part of the National Confidential Inquiry into Suicide and Homicide by People with Mental Illness.23 This revealed that healthcare providers who had a policy regarding how to manage patients who are not taking their medication as prescribed had 20% fewer suicides than providers who did not have such a policy.23 Another reason that poorly adherent individuals do worse is that they may stop their medication abruptly and without monitoring (and without telling anyone). Abrupt cessation of almost all psychotropic drugs tends to worsen prognosis (see The Maudsley Deprescribing Guidelines). One of the findings that clearly illustrate the benefits of adherence is the example of depot antipsychotic medications. They do not differ pharmacologically from their oral equivalents but have consistently been shown to result in lower rates of readmission to 05 - Factors affecting adherence7,28 Factors affecting adherence7,28 06 - Assessing adherence29,30 Assessing adherence29,30 Prescribing psychotropics CHAPTER 14 hospital. The only difference is that with the depot preparations, adherence is, for a while at least, assured (and known about) – something which cannot be said for oral medications. Improving adherence offers substantial possibilities for improving the outcomes from treatments. WHO comments that ‘increasing the effectiveness of adherence interventions may have far greater impact on the health of the population than any improvements in specific medical treatments’.1 We must also remember that medication is not the only effective treatment for psychosis. Although a meta-­analysis24 and systematic review25 of such psychodynamic interventions (which included studies in unmedicated patients) confirmed the superiority of treatment with antipsychotics, the most recent systematic review of psychosocial interventions for psychotic patients (with no or low-­dose antipsychotics) found the effect of such interventions to be equal to treatment with antipsychotics.26 Cognitive behavioural therapy (CBT) for psychosis has been demonstrated to reduce certain symptoms, although its effect on quality of life does not seem to be significant.27 So – we certainly need better drugs, but we need also to improve adherence. Factors affecting adherence7,28 Table 14.1 lists many of the factors that might affect adherence. Clearly, not all of these factors necessarily fit into a single category. For example, poor understanding by the patient can either be due to poor health literacy and/or numeracy or can be due to deficiencies in communication by the doctor. Assessing adherence29,30 Table 14.2 outlines methods of assessing medication adherence. For some antipsychotics such as clozapine, olanzapine, aripiprazole and risperidone, blood tests can be used to directly assess plasma levels. However, the plasma levels of these drugs attained with a fixed dose do vary, as do the therapeutic effects in individuals. It is therefore not possible to accurately determine partial non-­adherence. That is to say, total non-­adherence will be readily revealed (plasma level = zero) but partial and full adherence may be difficult to tell apart. Table 14.1  Factors affecting adherence. Illness-­related Treatment-­related Clinician-­related Patient-­related Environmental Lack of motivation Poor insight Grandiose delusions Cognitive deficit Thought disorder Forgetfulness Disorganisation Adverse effects Dysfunctional beliefs Inappropriate medication preparation or packaging Dosing schedules31,32 Poor therapeutic alliance Lack of follow-­up Limited consultation time Poor provision of information and explanation Denial Poor insight Comorbidities Physical impairments Poor literacy Poor health literacy33 Poor understanding of treatment options Disorganised environment Family’s beliefs Religious beliefs Health beliefs 930 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 14 Table 14.2  Assessing adherence. Method Variables measured Advantages Disadvantages Direct Blood test Drug/metabolite plasma levels Accurate Invasive Costly Inter-­individual variations (e.g. fast and slow metabolisers) Not reliable for all drugs (see text) Only a result of zero can be definitively interpreted Information only relevant for a very limited timeframe No information about the patterns of medication-­taking behaviour, levels of adherence or factors that may change adherence Indirect Pill count Number of missing tablets/ missed prescriptions Simple to use (useful in clinical trials) Labour-­intensive in clinical practice Substantial evidence that pill counts underestimate levels of non-­adherence Electronic database: clinical/pharmacy records History of non-­adherence (but generally with very little detail or formal assessment) Pharmacy dispensing and collection records (e.g. medication possession ratio – MPR) Readily accessible Easy to identify non-­adherent patients Inexpensive Non-­invasive Not reliable – only provides evidence for collection and possession of medication Self-­report Validated assessment scales (questionnaires) (e.g. Medication Adherence Rating Scale – MARS) Easy to use Inexpensive Subject to reporting bias Tendency to please clinicians Massively overestimates adherence Subjective Electronic monitoring devices (e.g. Medication Event Monitoring System – MEMS) Number of times medication container has been opened and (assumed) percentage of doses removed Among the most accurate methods Objective Provides additional information on medication-­taking behaviour Expensive Bulky containers Not evidence for ingestion of medication – only of container opening Patient feels under surveillance 07 - Monitoring adherence and assessing attitudes Monitoring adherence and assessing attitudes to medication 08 - Enhancing medication adherence Enhancing medication adherence Prescribing psychotropics CHAPTER 14 Monitoring adherence and assessing attitudes to medication Psychiatrists generally prefer to use direct questioning over the use of more intrusive/ objective and elaborate methods of assessing adherence. Partly as a result non-­adherence may go undetected.34 NICE recommends that the patient should be asked in a non-­ judgemental way if they have missed any doses over a specific time period such as the previous week.35 Issues of forgetfulness aside, whether the patient takes medication or not will be, to a significant extent, determined by their views about medication and its perceived effect on their life and condition. Rating scales and checklists can help the clinician to guide and structure a discussion of what the patient thinks and feels about medication. The most widely used is the Drug Attitude Inventory (DAI),36 which consists of a mix of positive and negative statements about medication; 30 statements in its full form and 10 in its short form. The patient completes it by simply agreeing or disagreeing with each statement. The total score is an indicator of the patient’s overall perception of the balance between the benefits and harms associated with taking medication, and therefore likely adherence. Attitudes to medication as measured in this way have been shown to be a useful predictor of adherence over time.37 Other checklists include the Rating of Medication Influences (ROMI) scale,38 the Beliefs about Medicines Questionnaire39 and the Medication Adherence Rating Scale (MARS).19 Enhancing medication adherence Adherence to medication requires collaboration between the patient and the prescriber. NICE recommends that, as long as the patient has capacity to consent, their right not to take medication should be respected. If the prescriber considers that this decision may lead to harm, the reasons for the patient’s decision and the prescriber’s concerns should be recorded. Adherence is a complex behaviour that is influenced by malleable underlying factors. Consequently, determinants of non-­adherence can be modified through patient-­specific and factor-­focused interventions (Table  14.3). However, most adherence-­enhancing interventions are not based on a sound theoretical framework and lack methodological rigour.40 Low-­quality studies and their outcomes are often not duplicated in different settings. This phenomenon was also highlighted by the most recent Cochrane review of adherence interventions when they reported that only 11 studies out of 182 included papers had the lowest risk of bias.41 Strategies for improving adherence Systematic reviews suggest that patient-­specific interventions are more likely to enhance adherence in patients with serious mental disorders.42 NICE has reviewed the evidence for adherence over a range of health conditions and concluded that no specific intervention can be recommended for all patients. Note that few studies in this area specifically recruited non-­adherent patients (the refusal rate in such patients is likely to be high) and the specific barriers to adherence are rarely identified. The small effect size seen in many studies may simply be a consequence of this unfocused approach. An intervention mapping framework43 provides a way to connect determinants of non-­adherence to evidence-­based interventions. 932 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 14 Medication-­taking aids ‘Compliance aids’ are boxes that contain compartments that can accommodate up to four doses of multiple medicines each day. These may be helpful in patients who are clearly motivated to take medication but who are disorganised or who have cognitive deficits. But only 10% of non-­adherent patients say that they simply forgot to take medication, so medication-­taking aids are not a substitute for lack of insight or lack of motivation. Moreover, some medicines are unstable when removed from blister packaging and placed in a compliance aid. These include oro-­dispersible formulations which are often prescribed for non-­adherent patients. In addition, medication-­taking aids are labour-­intensive (expensive) to fill, it can be difficult to change prescriptions at short notice and the process of filling of these devices is particularly error-­prone.46 More sophisticated programmes of practical support, both electronic and in-­person, have been shown to be effective.47 Depot/long-­acting antipsychotics Meta-­analyses of clinical trials have shown that the relative and absolute risks of relapse with depot maintenance treatment were 30% and 10% lower, respectively, than with oral treatment.48,49 NICE recommends that depots are an option in patients who are known to be non-­adherent to oral treatment and/or those who prefer this method of administration. However, it is worth remembering that switching a non-­ adherent patient from oral antipsychotics to a long-­acting injectable formulation does not address the underlying reasons driving that non-­adherence. This has been highlighted by a recent systematic review that reported a rate of discontinuation of above 50% in those who had been prescribed second-­generation depots.50 So long-­acting antipsychotics do not stop non-­adherence but they do prevent sudden cessation of medication and its consequences (all depots provide a slow decline in plasma levels). Table 14.3  Interventions for non-­adherence.44 Intentional non-­adherence Unintentional non-­adherence Psychoeducation is the foundation for all adherence interventions, but without behaviour-­changing components it is not overwhelmingly effective. Provides both verbal and written information. Motivational interviewing for goal-­setting Adherence therapy for exploring dysfunctional beliefs about medication or the illness, providing information and goal setting. It requires more time and multiple sessions. Cognitive behavioural therapy to eradicate or control the residual symptoms that prevent adherence. To address dysfunctional beliefs about treatment. Cognitive remediation to help with cognitive deficit in psychotic patients and thought disorder Mindfulness to help with symptoms Monitor adverse effects regularly and periodically Therapeutic alliance – a non-­judgemental clinician allows patients to honestly disclose their thoughts and beliefs about medication Family intervention – psychoeducation and family therapy Simplify dose regimen – reduce number of medications and/or frequency of administration Dispensing interventions – medication-­taking aids EAM (electronic adherence monitoring) – evidence for this is weak45 Pairing-­up medication – taking with a daily activity (e.g. having breakfast, brushing teeth or before bedtime) Use technology – messaging service, email and telephone reminders Pharmacy interventions for those with physical impairment (e.g. opening bottles) Prescribing psychotropics CHAPTER 14 Their use can also provide certainty about the level of adherence (the injection is either given or it is not). Depots are probably underused, for example a US study found that depot preparations were prescribed for fewer than one in five patients with a recent episode of non-­adherence.51 An alternative to depots is the use of long-­acting oral antipsychotics such as penfluridol, which can be given weekly.52 Supervised administration obviates the need for injections but does not provide the same level of certainty over compliance given the facility that patients have demonstrated for disguising the taking of oral medication. In the USA, Abilify MyCite is approved for use.53 This is a version of aripiprazole with a transmitting sensor embedded in the formulation which is able to confirm that a tablet has been taken. Evidence for its effectiveness is slim.54 Financial incentives Controlled trials in a number of disease areas support the offer of financial incentives to enhance medication adherence. Paying people to take their medication is extremely controversial, though some clinicians have found this strategy to be effective. The effect could not be maintained in a randomised controlled trial (RCT) at 6-­ and 24-­month follow-­up after payments were stopped, and complete adherence was achieved in only 28% of patients receiving the incentives.55 Other RCTs also have demonstrated a significant increase in adherence during the trial and a decline at follow-­up when payments had stopped.56 Offering financial incentives did not reduce patients’ motivation for treatment.57 A systematic review of acceptability of financial incentives for health-­ related behaviours has raised concerns about the validity and reliability of these interventions given their methodological limitations.58 Psychological interventions In physical medicine, medication adherence has been found to be associated with health beliefs and psychological variables, such as self-­efficacy and locus of control.59 Family support is also positively related to medication adherence. It is likely to be the same in psychiatry – but what can be done? One such intervention  – called, at the time, ‘compliance therapy’  – was evaluated at the Maudsley Hospital.60 This was a pilot of a mixed intervention, consisting of active listening, cognitive behavioural techniques, motivational interviewing and the provision of information and explanation. This showed promising results in terms of increased adherence and reduced admission rates over the next 6 months. However, training for staff and supervision render it time-­consuming. A subsequent replication did not show the same improvements,61 but also did not appear to have incorporated a training or supervisory element for those delivering the therapy. However, a trial of training in compliance therapy did seem to have an effect on the junior doctors involved, who felt that they were more aware of the drivers of non-­adherence and of the importance of empathic listening and more able to understand why a patient might not take medication.62 One prerequisite for successful adherence to a treatment regimen should be that the patient understands the objectives of treatment, the options on offer and the rationale behind them. However, many – perhaps most – doctors have had no specific training in how to convey information and understanding to patients. Difficulties have been noted 09 - Conclusion Conclusion 10 - References References 934 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 14 to arise in cancer medicine regarding the benefits and risks of anti-­cancer medications.63 One must assume that we are likely to meet the same difficulties in psychiatry. We also need to consider that our patients may have a very different explanatory model for what is happening to them. For example, not so long ago, only just over a third of white English patients viewed schizophrenia as having a substantially biological origin.64 So our explanations for a person’s psychosis may not be as convincing to them – and their families – as we might imagine. One simple step that might help is to encourage patients with a serious medical illness to read their own notes; one study reported that this helped such patients to better understand why they were prescribed medications.65 However, this begs the question of why they did not understand in the first place. The range of practical interventions described in Table 14.3 – and, to a great extent, the psychological interventions contained in the original model of compliance therapy – will need to be tailored to the needs of the individual patient. But this assumes that clinicians have an awareness of the issue, the requisite skills and the time available to use them. The current RCPsych curricula, although they refer to some of the psychological skills modalities mentioned, do not include the management of adherence as an issue in either the core curriculum or the general psychiatry curriculum.66 Conclusion Establishing and maintaining adherence is a quintessentially biopsychosocial activity. It is central to the practice of medicine and, hence, to psychiatry. It demands both an awareness of the problem, a knowledge of practical strategies for its improvement and a repertoire of psychological skills. The neglect of this area of therapeutics in training should not deter prescribers from recognising non-­adherence and taking active steps to manage it. An initial gambit might be, at the end of any first prescription, to ask ourselves ‘What have I done to help this patient take this medication?’ and to record this answer as part of the care plan, as a reminder to ourselves and our colleagues that this issue needs our conscious, structured and regular attention. References World Health Organization. Adherence to long-­term therapies: evidence for action. 2003; https://apps.who.int/iris/bitstream/handle/ 10665/42682/9241545992.pdf. National Institute for Health and Care Excellence. Medicines adherence: involving patients in decisions about prescribed medicines and supporting adherence. Clinical guideline [CG76]. 2009 (last checked August 2023); https://www.nice.org.uk/guidance/cg76. Piatkowska O, et al. Medication —­ compliance or alliance? A client-­centred approach to increasing adherence. In: Kavanagh DJ, ed. Schizophrenia: An Overview and Practical Handbook. Boston, MA: Springer US; 1992:339–355. Bond C, et al. Prescribing and partnership with patients. Br J Clin Pharmacol 2012; 74:581–588. Sweetman J, et al. Risk factors for initial appointment non-­attendance at Improving Access to Psychological Therapy (IAPT) services: a retrospective analysis. Psychother Res 2023; 33:535–550. Foley L, et al. Prevalence and predictors of medication non-­adherence among people living with multimorbidity: a systematic review and meta-­analysis. BMJ Open 2021; 11:e0987. Semahegn A, et al. Psychotropic medication non-­adherence and its associated factors among patients with major psychiatric disorders: a systematic review and meta-­analysis. Syst Rev 2020; 9:17. Masand PS, et al. Partial adherence to antipsychotic medication impacts the course of illness in patients with schizophrenia: a review. Prim Care Companion J Clin Psychiatry 2009; 11:147–154. Alosaimi K, et al. Medication adherence among patients with chronic diseases in Saudi Arabia. Int J Environ Res Public Health 2022; 19:10053. Leucht S, et al. Epidemiology, clinical consequences, and psychosocial treatment of nonadherence in schizophrenia. J Clin Psychiatry 2006; 67 Suppl 5:3–8. Prescribing psychotropics CHAPTER 14 11. Zhou Y, et al. Factors associated with complete discontinuation of medication among patients with schizophrenia in the year after hospital discharge. Psychiatry Res 2017; 250:129–135. 12. Cramer JA, et al. Compliance with medication regimens for mental and physical disorders. Psychiatr Serv 1998; 49:196–201. 13. Geretsegger C, et al. Non-­adherence to psychotropic medication assessed by plasma level in newly admitted psychiatric patients: prevalence before acute admission. Psychiatry Clin Neurosci 2019; 73:175–178. 14. Remington G, et al. The use of electronic monitoring (MEMS) to evaluate antipsychotic compliance in outpatients with schizophrenia. Schizophr Res 2007; 90:229–237. 15. McCutcheon R, et al. Antipsychotic plasma levels in the assessment of poor treatment response in schizophrenia. Acta Psychiatr Scand 2018; 137:39–46. 16. Taipale H, et al. 20-­year follow-­up study of physical morbidity and mortality in relationship to antipsychotic treatment in a nationwide cohort of 62,250 patients with schizophrenia (FIN20). World Psychiatry 2020; 19:61–68. 17. Morken G, et al. Non-­adherence to antipsychotic medication, relapse and rehospitalisation in recent-­onset schizophrenia. BMC Psychiatry 2008; 8:32. 18. Knapp M, et al. Non-­adherence to antipsychotic medication regimens: associations with resource use and costs. Br J Psychiatry 2004; 184:509–516. 19. Jaeger S, et al. Adherence styles of schizophrenia patients identified by a latent class analysis of the Medication Adherence Rating Scale (MARS): a six-­month follow-­up study. Psychiatry Res 2012; 200:83–88. 20. Lang K, et al. Predictors of medication nonadherence and hospitalization in Medicaid patients with bipolar I disorder given long-­acting or oral antipsychotics. J Med Econ 2011; 14:217–226. 21. Mitchell AJ, et al. Why don’t patients take their medicine? Reasons and solutions in psychiatry. Adv Psychiatric Treat 2007; 13:336–346. 22. Scherrer JF, et al. Antidepressant drug compliance: reduced risk of MI and mortality in depressed patients. Am J Med 2011; 124:318–324. 23. Appleby L, et al. National Confidential Inquiry into Suicide and Homicide by People with Mental Illness. 2013; http://www.bbmh.manchester. ac.uk/cmhr/research/centreforsuicideprevention/nci/. 24. Malmberg L, et al. Individual psychodynamic psychotherapy and psychoanalysis for schizophrenia and severe mental illness. Cochrane Database Syst Rev 2001; 3:CD001360. 25. Mueser KT, et al. Psychodynamic treatment of schizophrenia: is there a future? Psychol Med 1990; 20:253–262. 26. Cooper RE, et al. Psychosocial interventions for people with schizophrenia or psychosis on minimal or no antipsychotic medication: a systematic review. Schizophr Res 2019; 225:15–30. 27. Health Quality Ontario. Cognitive behavioural therapy for psychosis: a health technology assessment. Ont Health Technol Assess Ser 2018; 18:1–141. 28. Pedley R, et al. Qualitative systematic review of barriers and facilitators to patient-­involved antipsychotic prescribing. BJPsych Open 2018; 4:5–14. 29. Forbes CA, et al. A systematic literature review comparing methods for the measurement of patient persistence and adherence. Curr Med Res Opin 2018; 34:1613–1625. 30. Anghel LA, et al. An overview of the common methods used to measure treatment adherence. Med Pharmacy Rep 2019; 92:117–122. 31. Greenberg RN. Overview of patient compliance with medication dosing: a literature review. Clin Ther 1984; 6:592–599. 32. Saini SD, et al. Effect of medication dosing frequency on adherence in chronic diseases. Am J Manag Care 2009; 15:e22–33. 33. Miller TA. Health literacy and adherence to medical treatment in chronic and acute illness: a meta-­analysis. Patient Educ Couns 2016; 99:1079–1086. 34. Vieta E, et al. Psychiatrists’ perceptions of potential reasons for non-­ and partial adherence to medication: results of a survey in bipolar disorder from eight European countries. J Affect Disord 2012; 143:125–130. 35. National Institute for Health and Care Excellence. Psychosis and schizophrenia in adults: prevention and management. Clinical guideline [CG178]. 2014 (last checked August 2023); https://www.nice.org.uk/guidance/cg178. 36. Hogan TP, et al. A self-­report scale predictive of drug compliance in schizophrenics: reliability and discriminative validity. Psychol Med 1983; 13:177–183. 37. Perkins DO. Predictors of noncompliance in patients with schizophrenia. J Clin Psychiatry 2002; 63:1121–1128. 38. Weiden P, et al. Rating of medication influences (ROMI) scale in schizophrenia. Schizophr Bull 1994; 20:297–310. 39. Horne R, et al. The beliefs about medicines questionnaire: the development and evaluation of a new method for assessing the cognitive representation of medication. Psychol Health 1999; 14:1–24. 40. Zullig LL, et al. Moving from the trial to the real world: improving medication adherence using insights of implementation science. Annu Rev Pharmacol Toxicol 2019; 59:423–445. 41. Nieuwlaat R, et al. Interventions for enhancing medication adherence. Cochrane Database Syst Rev 2014; 11:CD000011. 42. Nosè M, et al. [Systemic review of clinical interventions for reducing treatment non-­adherence in psychosis]. Epidemiol Psichiatr Soc 2003; 12:272–286. 43. Kok G, et al. A taxonomy of behaviour change methods: an intervention mapping approach. Health Psychol Rev 2016; 10:297–312. 44. Hartung D, et al. Interventions to improve pharmacological adherence among adults with psychotic spectrum disorders and bipolar disorder: a systematic review. Psychosomatics 2017; 58:101–112. 45. Chan AHY, et al. Effect of electronic adherence monitoring on adherence and outcomes in chronic conditions: a systematic review and meta-­analysis. PLoS One 2022; 17:e0265715. 46. Barber ND, et al. Care homes’ use of medicines study: prevalence, causes and potential harm of medication errors in care homes for older people. Qual Safety Health Care 2009; 18:341–346. 936 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 14 47. Velligan D, et al. A randomized trial comparing in person and electronic interventions for improving adherence to oral medications in schizophrenia. SchizophrBull 2013; 39:999–1007. 48. Leucht C, et al. Oral versus depot antipsychotic drugs for schizophrenia – a critical systematic review and meta-­analysis of randomised long-­term trials. Schizophr Res 2011; 127:83–92. 49. Leucht S, et al. Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-­analysis. Lancet 2012; 379:2063–2071. 50. Gentile S. Discontinuation rates during long-­term, second-­generation antipsychotic long-­acting injection treatment: a systematic review. Psychiatry Clin Neurosci 2019; 73:216–230. 51. West JC, et al. Use of depot antipsychotic medications for medication nonadherence in schizophrenia. Schizophr Bull 2008; 34:995–1001. 52. Soares BG, et al. Penfluridol for schizophrenia. Cochrane Database Syst Rev 2006; 2:CD002923. 53. Otsuka Pharmaceutical Co. Ltd. Highlights of prescribing information. Abilify Mycite (aripiprazole with sensor) for oral use 2017. https:// www.accessdata.fda.gov/drugsatfda_docs/label/2017/207202lbl.pdf. 54. Cosgrove L, et al. Digital aripiprazole or digital evergreening? A systematic review of the evidence and its dissemination in the scientific literature and in the media. BMJ Evid Based Med 2019; 24:231–238. 55. Priebe S, et al. Financial incentives to improve adherence to antipsychotic maintenance medication in non-­adherent patients: a cluster randomised controlled trial. Health Technol Assess 2016; 20:1–122. 56. Noordraven EL, et al. Financial incentives for improving adherence to maintenance treatment in patients with psychotic disorders (Money for Medication): a multicentre, open-­label, randomised controlled trial. Lancet Psychiatry 2017; 4:199–207. 57. Noordraven EL, et al. The effect of financial incentives on patients’ motivation for treatment: results of ‘Money for Medication,’ a randomised controlled trial. BMC Psychiatry 2018; 18:144. 58. Hoskins K, et al. Acceptability of financial incentives for health-­related behavior change: an updated systematic review. Prev Med 2019; 126:105762. 59. Marrero RJ, et al. Psychological factors involved in psychopharmacological medication adherence in mental health patients: a systematic review. Patient Educ Couns 2020; 103:2116–2131. 60. Kemp R, et al. Compliance therapy in psychotic patients: randomised controlled trial. BMJ 1996; 312:345–349. 61. O’Donnell C, et al. Compliance therapy: a randomised controlled trial in schizophrenia. BMJ 2003; 327:834. 62. Surguladze S, et al. Teaching psychiatric trainees ‘compliance therapy’. Psychiatric Bull 2002; 26:12–15. 63. Davis C, et al. Communication of anticancer drug benefits and related uncertainties to patients and clinicians: document analysis of regulated information on prescription drugs in Europe. BMJ 2023; 380:e073711. 64. McCabe R, et al. Explanatory models of illness in schizophrenia: comparison of four ethnic groups. Br J Psychiatry 2004; 185:25–30. 65. Blease C, et al. Association of patients reading clinical notes with perception of medication adherence among persons with serious mental illness. JAMA Netw Open 2021; 4:e212823. 66. Royal College of Psychiatrists. Curricula documents and resources. 2022; https://www.rcpsych.ac.uk/training/curricula-­and-­guidance/ curricula-­implementation/curricula-­documents-­and-­resources. 11 - Restarting psychotropic medications after a p Restarting psychotropic medications after a period of non-compliance Prescribing psychotropics CHAPTER 14 Restarting psychotropic medications after a period of non-­compliance When a patient is admitted to hospital it is often because they have been non-­compliant with their medications for some time before admission. The clinical question of whether to restart the medication and at which dose is a complex one. The risk of withdrawal symptoms and relapse must be balanced against the risk of adverse drug reactions when medications are reintroduced too quickly. There is little published evidence on this area, with most guidance (often of undeclared provenance) coming from manufacturers. The guidance below should be followed with caution. Summaries of product characteristics (SPCs) and other formal, regulatory documents tend not to deal with the issue of restarting medication. Official patient information leaflets sometimes give detailed advice. These leaflets are unanimous in advising that on no account should a double dose be given to make up for a missed dose. However, the vast majority of leaflets advise only on what to do if a single dose has been missed. Some leaflets advise taking the missed dose later (providing it is not too close to the next dose), whereas others recommend skipping the missed dose altogether and starting again with the next dose. In the event that more than one dose has been missed, the first question to ask is whether or not this is the appropriate drug for a patient to be taking. Poor compliance often indicates some dissatisfaction on the part of the patient. If it is a drug with a short half-­life or one that requires lengthy re-­titration, it may not be appropriate to restart prescribing for a patient who is frequently non-­compliant. Similarly, if a patient is intoxicated with alcohol or drugs, it may not be sensible to restart medication at that time. Efforts should be made to find out if there are any particular reasons for non-­ compliance. Where poor adherence is a result of factors other than tolerability, consider the use of a long-­acting injection (although these are only used, officially at least, in schizophrenia and schizoaffective disorder). When considering whether to restart the drug at the same dose as before or to re-­titrate from a lower dose, the time since the last dose is vitally important. If more than a week or two has passed, then all drugs will probably need to be restarted as if it is new treatment (although for many drugs that do not require titration this might mean starting back on the same dose as before). Exceptions include long-­acting depot formulations and oral drugs with long half-­lives such as aripiprazole, cariprazine and penfluridol. With these, there is a need to reload if the gap in treatment is very long, although shorter gaps (<2 weeks) might be managed by giving the usual dose and then reverting to the original dosing schedule. Lamotrigine must be considered separately from all other psychotropics because it has been associated with life-­threatening cutaneous reactions, especially with high initial doses. The manufacturer’s product information advises that if five half-­lives have elapsed since the last lamotrigine dose was given, lamotrigine should be titrated as if for the first time. The half-­life in healthy subjects on no other medication is around 33 hours. This is affected by other medications and is approximately 14 hours when given with glucuronidation-­inducing drugs such as carbamazepine or phenytoin. The half-­life is increased to approximately 70 hours when given with valproate. This means that the time before complete re-­titration is necessary varies between 3 and 7 days, depending on other drugs co-­prescribed.1 Table 14.4 summarises some very general recommendations. The drugs in the first column have specific safety issues that mean they require re-­titration after the specified 12 - References References 938 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 14 length of time. The drugs in the middle column are thought to be safe because the maximum dose is usually no higher than the highest recommended starting dose. The drugs in the right-­hand column are thought to be safe to restart at the prior dose because a similar drug appears in the middle column, because clinical experience suggests they are safe or because the risks associated with giving untitrated high doses are thought to be low. Some suggestions are obtained from EU regulatory documents (SPCs),2 while others are mere suggestions based on clinical experience. If the gap in oral treatment is longer than 2 weeks, start as if it is new treatment (noting the exceptions listed earlier). References Aurobindo Pharma-­Milpharm Ltd. Summary of product characteristics. Lamotrigine 25mg tablets. 2024 (last accessed September 2024); https://www.medicines.org.uk/emc/product/4736/smpc. EMC. Summaries of Product Characteristics. 2024 (last accessed September 2024); https://www.medicines.org.uk/emc/. Table 14.4  Restarting medication up to 2 weeks after stopping oral treatment. Drugs that require re-­titration Drugs that are usually safe for restarting at the previous dose Drugs that are possibly safe for restarting at the previous dose Drug Time after which re-­titration must be performed Further guidance Clozapine 48 hours See section in Chapter 1 Acamprosate Asenapine Fluoxetine Haloperidol Isocarboxazid Lofepramine Methylphenidate Phenelzine Sulpiride Tranylcypromine Valproate Antipsychotics (exceptions in column 1) Carbamazepine (beware loss on enzyme induction) Cholinesterase inhibitors CNS stimulants Disulfiram Lithium (titration advised if renal function has changed) MAOIs Memantine Naltrexone Pregabalin SSRIs Lamotrigine 3–7 days See text Methadone, buprenorphine 3 days See section in Chapter 4 Paliperidone long-­acting injection Depends on formulation See section in Chapter 1 Aripiprazole long-­acting injection Depends on formulation See section in Chapter 1 Quetiapine Suggest 1 week Tolerance to sedative and hypotensive effects may be lost Risperidone Suggest 1 week Tolerance to hypotensive effects may be lost Tricyclics Suggest 1 week Tolerance to sedative and hypotensive effects may be lost MAOIs, monoamine oxidase inhibitors. 13 - Relational aspects of prescribing practice Relational aspects of prescribing practice 14 - Object relations Object relations 15 - Memory Memory 16 - Treatment framework Treatment framework Prescribing psychotropics CHAPTER 14 Relational aspects of prescribing practice This section provides clinicians with practically useful advice in the relational aspects of prescribing. Evidence exists for the importance of the doctor–patient relationship in improving treatment outcomes.1–3 The key factors that help develop, maintain and deepen the relationship include instilling trust and regard.4 Three concepts are important here: object relations, memory and the treatment framework. Object relations This means how the individual views themselves and others around them. This view then influences how they process incoming data (e.g. what is happening in an interaction). This view of themselves has been determined from early experience. In essence it means that the present interaction may be experienced inaccurately through the prism of the past (another way to think of this experience is that this is the transference). This has implications for both the patient and the clinician. For example, if the patient has had early experience of uncaring parents, they will have greater difficulty in trusting the clinician. In turn, if the clinician’s early experience is of demanding parents who expected them to always get it right, a treatment-­resistant patient may be a particular challenge for them. This object relations approach allows one to be aware of factors regarding the patient, the clinician and the clinician– patient relationship. Memory Up to 95% of our goal-­directed activities are executed unconsciously.5 Thus, the clinician’s prescribing may be more influenced by procedural memory than their subjective view that they are using working memory (i.e. there is an illusion of the application of active thinking to solve the specificity of the present problem). By definition, procedural memory and the action flowing from this may not be best suited for a particular clinical situation. Acknowledging the unconscious influence on the present may help bring the conscious mind into play. Treatment framework This is using knowledge of the clinician’s usual way of working (e.g. following this edition of The Maudsley Prescribing Guidelines), and a knowledge of how they tend to personally apply these guidelines. Straying from the guidelines may be based on good clinical judgement but also it may indicate that there is some psychological factor influencing decision-­making. Given this psychological factor may be unconscious, the ability to review ‘what one usually does’ is then a useful check on what may be happening in prescribing. For example, if the prescriber is able to think ‘I do not usually prescribe such a high dose of antipsychotic as a starting dose’ they may then be able to pose the question ‘Am I feeling very anxious to satisfy the demands of this patient?’ In effect they may then be able to catch themselves acting out (i.e. replacing thinking with behaviour) in the countertransference (in this case their great anxiety to satisfy the patient). 17 - Factors that may influence the patients use o Factors that may influence the patient’s use of and adherence to medication 940 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 14 Factors that may influence the patient’s use of and adherence to medication How the individual views themselves, and others, will influence many aspects of a person’s behaviour. These issues include their personal and cultural beliefs, readiness to change, ambivalence, expectations of treatment, attachment style and treatment preference. In addition, patients might use medication in countertherapeutic ways. We address each of these in turn in terms of their practical implications.6,7 Personal and cultural beliefs The religious, cultural and socioeconomic contexts shape our beliefs around concepts of illness, health and disability.8 Adherence to treatments is affected by the patient’s subjective beliefs and averages roughly 50% in almost all conditions.9 Recommendation: When it comes to prescribing within a culturally diverse population, prescribers need to reflect on their own cultural biases, enquire about the patient’s cultural beliefs, and work collaboratively with communities and families.10 Readiness to change Patients’ motivation and readiness to change can affect treatment outcomes. Beitman et al.11 examined stages of change and response to medication in patients with panic disorder and found that readiness to change was associated with better outcomes. The transtheoretical model12 proposes that people move through different stages of change and that interventions must match the stage of readiness. This model can also be useful for the treatment of other mental health conditions including personality disorder.13 Recommendation: The clinician’s appreciation of the stages of change, and the work involved in lasting change, can increase compassion and avoid wrongly timed interventions (including wrongly timed prescribing). A recovery-­focused and patient-­centred approach may help patients to understand entrenched patterns of behaviour, and to actively participate in behavioural change. Ambivalence Patients may worry about the safety of psychotropics, and mistrust clinicians. Further, symptoms may have an adaptive and protective function thus making them harder for the patient to relinquish. For example, a patient who has elicited care might be ambivalent about getting better and losing this care. Recovery might portend, for example, confronting a difficult relationship or working through an intolerable loss.14 Recent advances in the field of neuropsychoanalysis suggest that unpleasurable feelings at a biological level indicate that the patient’s underlying emotional needs are not being satisfied, serving as homeostatic ‘error signals’. It is not a surprise then that symptoms (associated with feelings states) can be stubbornly resistant to symptom-­focused treatments when the patient’s basic emotional needs continue to be unmet.15 Recommendation: Exploring patients’ ambivalence towards medication and healthcare professionals, and their previous experiences of care, can deepen the therapeutic relationship and is crucial in understanding patients’ concerns. Understanding the Prescribing psychotropics CHAPTER 14 patient’s (often unconscious) underlying conflicts and motivations can explain symptom perseverance despite pharmacological endeavours. Acknowledgement of the patient’s ambivalence during the recovery process may help validate their experience, facilitate rapport and enable conversations that the patient might otherwise be reluctant to approach. Expectations of treatment: placebo and nocebo effect Expectations of improvement or harm when taking medication exert a significant impact on treatment responses. The powerful ‘placebo’ response has been well described in medicine as a genuine psychobiological event.16 Conversely, expectations of harm are associated with negative treatment outcomes known as the ‘nocebo’ effect. Patients often expect harm from taking antidepressants, fearing dependence and loss of control of their emotions.17 Interestingly, patients who discussed adverse effects of antidepressants with their doctors were reported less likely to discontinue therapy than patients who did not discuss them.18 Recommendation: These findings emphasise the need to use all the elements of the therapeutic relationship in the care of patients.19 Clinical management of the nocebo effect includes awareness and recognition, focusing on the treatment alliance, carefully naming and working through mistrust, and careful disclosure of potential drug-­related adverse effects, while remaining honest and clear.20 Attachment style Healthcare staff often represent attachment figures21 as they treat patients in times of need and distress. The attachment is particularly important when it comes to the management of long-­term conditions. In one study, diabetic patients with dismissive attachment had significantly worse glucose control than patients with preoccupied or secure attachment style, but the effect was mitigated by improved communication between doctors and patients.22,23 Concerns about rejection, abandonment, control and intimacy24 are likely to affect patients’ use of their medication. Patients with a dismissive attachment style may fear dependence on medication and services and not adhere to the prescribed interventions. Patients with a fearful-­anxious attachment might need regular reassurance, while patients with a disorganised attachment might evoke disorganised and chaotic responses from healthcare staff. Recommendation: Consider attachment patterns when prescribing. Particular attention and consistency are needed to deliver coherent and reliable care alongside pharmacological interventions. Treatment preference The chronic illness model encourages consideration of the patient’s treatment preferences. Research suggests that matching treatment to preference might improve outcomes for patients with depression.25 An RCT matching patients to treatment preference for major depressive disorder concluded that patients had better outcomes on their preferred treatment.26 These observations might apply to other conditions. 18 - Summary a checklist when prescribing Summary – a checklist when prescribing 942 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 14 Recommendation: Consider treatment preference as one of the decision factors when prescribing. Countertherapeutic use of medication Medication (including overdose) may be used as a way of signalling submission, anger or helplessness. This is especially true in people who lack an emotional vocabulary and secure internal representations of benign care. Medication may become a way of self-­ management, replacing more developmental coping strategies and relationships. Recommendation: The clinician should consider the meaning of the emotional communication and be curious about alliance ruptures and system failures (and therefore reflect on the clinician’s possible contributions to the rupture). Summary – a checklist when prescribing When faced with complex prescribing decisions, a checklist considering the discussed issues from the perspective of the patient, the clinician and the clinician–patient relationship may be helpful. The patient factor Q: ‘What is my patient’s story? What is my patient trying to communicate using words or, as important, through their actions in the here and now?’ Recommendation: A formulation of the patient’s underlying psychological difficulties may help. This may include: ■ ■Predominant relational pattern(s) – attachment style and relationship to care/ authority. ■ ■Ambivalence about symptoms – underlying psychological investment in status quo. ■ ■Meaning attached to medication and overall use of medication (including countertherapeutic use of medication). The clinician factor Q: ‘How do I feel in response to my patient and how does that influence the action I am considering taking (e.g. do I feel helpless, frustrated, incompetent, guilty in the face of the patient’s symptoms)? Am I prescribing to avoid unwanted feelings in my relationship with my patient?’ Recommendation: 1 The first step in identifying countertransference pressure is to recognise and accept it, without always resorting to immediate action. 2 Self-­review of practice. The clinician may ask: ■ ■Am I working within relevant guidelines? ■ ■Am I doing what I normally do (if not, am I being overly influenced by my countertransference)? ■ ■Do I have strong feelings about this patient? Do I have no feelings about this patient? (Which would be also worth considering.) Prescribing psychotropics CHAPTER 14 ■ ■Are any circumstances different, for example do I have managers or other colleagues or the patient’s family scrutinising me with this particular patient? 3 Seek support. Use supervision with colleagues and ask support from other members of the multidisciplinary team. It is important to work closely with colleagues (including pharmacists) to triangulate decisions when in complex prescribing dilemmas. Choosing to discuss a problem in supervision and outside of the heat of the consulting room can clarify thinking. The clinician–patient relationship Q: ‘What might prescribing a medication – or not prescribing – come to represent in my relationship with my patient?’ Limited consultation time and cancelled clinics might reinforce feelings of rejection and abandonment. Non-adherence to medication or overdose of prescribed medication might be a sign of a rupture in the clinician–patient relationship and further exploration can promote useful insights for patient and clinician. Recommendation: Consider the meaning of medication in the context of the patient, the clinician and the clinician–patient relationship. Cultivate a pharmacotherapeutic partnership and set limits:24 ■ ■Reframe prescribing as a partnership, rather than a one-­directional activity of the doctor. ■ ■Provide, as much as possible, a stable and consistent consultation setting. ■ ■Set therapeutic limits, confronting unrealistic expectations of care. (This includes maintaining a realistic humility around the limitations of psychopharmacology, and psychoeducating patients regarding what medications can and cannot achieve and their place in the overall journey to recovery and development.) ■ ■Endorse a stance that can promote the pharmacotherapeutic alliance, characterised by emotional presence and warmth, good and honest communication, and support of the patient’s autonomy and agency. This includes shared decision-­making and respect for the patient’s treatment preferences, when clinically indicated. ■ ■Openly discuss overall recovery goals, target symptoms, duration of treatment and potential adverse effects, and address any associated anxieties. ■ ■A clear agreement on treatment objectives, consistent with the overall care plan, and the respective responsibilities of doctor and patient can promote agency and strengthen the pharmacotherapeutic partnership. ■ ■Collaborative crisis planning should be part of this, especially when there are risk concerns. 19 - References References 944 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 14 References Olaisen RH, et  al. Assessing the longitudinal impact of physician-­patient relationship on functional health. Ann Fam Med 2020; 18:422–429. McKay KM, et al. Psychiatrist effects in the psychopharmacological treatment of depression. J Affect Disord 2006; 92:287–290. Kelley JM, et al. The influence of the patient-­clinician relationship on healthcare outcomes: a systematic review and meta-­analysis of randomized controlled trials. PLoS One 2014; 9:e94207. Ridd M, et  al. The patient-­doctor relationship: a synthesis of the qualitative literature on patients’ perspectives. Br J Gen Pract 2009; 59:e116–e133. Bargh JA, et al. The unbearable automaticity of being. Am Psychol 1999; 54:462. Mintz DL, et  al. How (not what) to prescribe: nonpharmacologic aspects of psychopharmacology. Psychiatr Clin North Am 2012; 35:143–163. Konstantinidou H, et al. Will this tablet make me happy again? The contribution of relational prescribing in providing a pragmatic and psychodynamic framework for prescribers. BJPsych Advances 2023; 29:265–273. Ravindran N, et al. Cultural influences on perceptions of health, illness, and disability: a review and focus on autism. J Child Fam Studies 2012; 21:311–319. Lam WY, et al. Medication adherence measures: an overview. BioMed Res Int 2015; 2015:217047. Brooks LA, et al. Culturally sensitive communication in healthcare: a concept analysis. Collegian 2019; 26:383–391. Beitman BD, et al. Patient stage of change predicts outcome in a panic disorder medication trial. Anxiety 1994; 1:64–69. Prochaska JO, et al. Stages and processes of self-­change of smoking: toward an integrative model of change. J Consult Clin Psychol 1983; 51:390–395. Roughley M, et al. Referral of patients with emotionally unstable personality disorder for specialist psychological therapy: why, when and how? BJPsych Bull 2021; 45:52–58. Gibbons R. The mourning process and its importance in mental illness: a psychoanalytic understanding of psychiatric diagnosis and classification. BJPsych Advances 2024; 30:80–88. Lee T, et al. Managing the clinical encounter with patients with personality disorder in a general psychiatry setting: key contributions from neuropsychoanalysis. BJPsych Advances 2023; doi:10.1192/bja.2023.43. Finniss DG, et al. Biological, clinical, and ethical advances of placebo effects. Lancet 2010; 375:686–695. Piguet V, et al. Patients’ representations of antidepressants: a clue to nonadherence? Clin J Pain 2007; 23:669–675. Bull SA, et  al. Discontinuation of use and switching of antidepressants: influence of patient-­physician communication. JAMA 2002; 288:1403–1409. Benedetti F. Placebo and the new physiology of the doctor-­patient relationship. Physiol Rev 2013; 93:1207–1246. Data-­Franco J, et al. The nocebo effect: a clinicians guide. Aust NZ J Psychiatry 2013; 47:617–623. Adshead G. Psychiatric staff as attachment figures. Understanding management problems in psychiatric services in the light of attachment theory. Br J Psychiatry 1998; 172:64–69. Ciechanowski PS, et al. The patient-­provider relationship: attachment theory and adherence to treatment in diabetes. Am J Psychiatry 2001; 158:29–35. Ciechanowski PS, et al. The association of patient relationship style and outcomes in collaborative care treatment for depression in patients with diabetes. Med Care 2006; 44:283–291. Mintz D. Psychodynamic Psychopharmacology: Caring for the Treatment-­Resistant Patient. Washington, DC: American Psychiatric Association Publishing; 2022. Lin P, et al. The influence of patient preference on depression treatment in primary care. Ann Behav Med 2005; 30:164–173. Kocsis JH, et al. Patient preference as a moderator of outcome for chronic forms of major depressive disorder treated with nefazodone, cognitive behavioral analysis system of psychotherapy, or their combination. J Clin Psychiatry 2009; 70:354–361. 20 - Prescribing drugs outside their licensed indi Prescribing drugs outside their licensed indications (‘off-label’ prescribing) Prescribing psychotropics CHAPTER 14 Prescribing drugs outside their licensed indications (‘off-­label’ prescribing) A Product Licence is granted when regulatory authorities are satisfied that the drug in question has proven efficacy in the treatment of a specified disorder, along with an acceptable adverse effect profile, relative to the severity of the disorder being treated and other available treatments. Licensed indications are preparation-­ specific, outlined in the SPCs, and may be different for branded and generic formulations of the same drug.1 In the USA, product ‘labelling’ has a similar legal status to EU licensing. The decision of a manufacturer to seek a Product Licence for a given indication is essentially a commercial one. Potential sales are balanced against the cost of conducting the necessary clinical trials. Drugs may be effective outside their licensed indications for different disease states, age ranges, doses and durations. The absence of a formal Product Licence or labelling may reflect the absence of controlled trials supporting the drug’s efficacy in these areas. In some cases (e.g. sertraline or quetiapine in generalised anxiety disorder [GAD]) there is sufficient evidence but a licence has not been sought by the manufacturer. Importantly, however, it is also possible that trials have been conducted but have given negative or equivocal results. Clinicians often assume that drugs with a similar mode of action will be similarly effective for a given indication. This may encourage the assumption that the official labelling for one drug indicates efficacy and safety of another, similar drug. However, apparently similar drugs may differ in respect to active metabolites and in regard to receptor affinity. Prescribing a drug within its licence or labelling does not guarantee that the patient will come to no harm. Likewise, prescribing outside a licence does not mean that the risk–benefit ratio is automatically adverse. For example, sertraline and fluoxetine are no less effective for GAD than alternative, licensed drugs.2 Prescribing outside a licence, usually called ‘off-­label’, does confer extra responsibilities on prescribers, who will be expected to be able to show that they acted in accordance with a respected body of medical opinion (the Bolam test)3 and that their action was capable of withstanding logical analysis (the Bolitho test).4 In the UK, both have effectively been superseded, or at least clarified, by the Montgomery vs Lanarkshire Health Board appeal case decision5 which stated: An adult person of sound mind is entitled to decide which, if any, of the available forms of treatment to undergo, and her consent must be obtained before treatment interfering with her bodily integrity is undertaken. The doctor is therefore under a duty to take reasonable care to ensure that the patient is aware of any material risks involved in any recommended treatment, and of any reasonable alternative or variant treatments. The test of materiality is whether, in the circumstances of the particular case, a reasonable person in the patient’s position would be likely to attach significance to the risk, or the doctor is or should reasonably be aware that the particular patient would be likely to attach significance to it. Thus, in the UK at least, the prescriber has a duty to make a patient aware of any material risks associated with the prescribing of any medicines and to outline alternatives. 946 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 14 The General Medical Council allows doctors to prescribe off-­label but only where the prescriber is satisfied that there is enough evidence or experience to support efficacy and safety.6 In the USA, it is lawful to prescribe off-­label ‘within a legitimate health care ­practitioner–patient relationship’.7 Marketing of off-­label use is forbidden but information may be provided following an unsolicited request.8 Off-­label prescribing represents a significant proportion of prescribing in mental health conditions in the USA.9,10 A similar degree of off-­label prescriptions is seen in other countries.11–13 Off-­label prescribing in psychiatry is less likely to be supported by a strong evidence base than off-­label prescribing in other areas of medicine.14 In psychiatry, small (underpowered) studies (with wide confidence intervals) often influence practice, particularly with respect to treatment-­resistant illness (a great many examples can be found in this book). When these small studies are combined in the form of a meta-­analysis, considerable heterogeneity is often found, suggesting publication bias (i.e. that some negative studies are not published). Treatments may therefore become incorporated into ‘routine custom and practice’ in the absence of robust evidence supporting efficacy and/or tolerability, and these treatments may sometimes continue to be used despite the findings of later, larger and more definitive negative studies and meta-­analyses. An example of widespread off-­label prescribing of a psychotropic in non-­mental health conditions is amitriptyline – 93% of UK primary care prescriptions are off-­label.15 The psychopharmacology special interest group at the Royal College of Psychiatrists published a consensus statement on the use of licensed medicines for unlicensed uses.16 They noted that unlicensed use is common in general adult psychiatry, with cross-­ sectional studies showing that up to 50% of patients are prescribed at least one drug outside the terms of its licence. They also note that the prevalence of this type of prescribing is likely to be higher in patients under the age of 18 or over 65, in those with a learning disability, in women who are pregnant or lactating and in those patients who are cared for in forensic psychiatry settings. The main recommendations in the consensus statement are summarised in Box 14.1. Box 14.1  Recommendations before prescribing ‘off-­label’ ■ ■Exclude licensed alternatives (e.g. they have proved ineffective or poorly tolerated). ■ ■Ensure familiarity with the evidence base for the intended unlicensed use. If unsure, seek advice from another clinician (and possibly a specialist pharmacist). ■ ■Consider and document the potential risks and benefits of the proposed treatment. Share this risk assessment with the patient, and carers if applicable. Document the discussion and the patient’s consent or lack of capacity to consent. ■ ■If prescribing responsibility is to be shared with primary care, ensure that the risk assessment and consent issues are shared with the GP. ■ ■Monitor for efficacy and adverse effects; start a low dose and increase slowly. ■ ■Consider publishing the case to add to the body of knowledge. ■ ■Withdraw any treatment that is ineffective or where emergent risks outweigh the benefits. The more experimental the unlicensed use is, the more important it is to adhere to the above guidance. 21 - Examples of acceptable use of drugs outside t Examples of acceptable use of drugs outside their licences/labels Prescribing psychotropics CHAPTER 14 The advice is largely echoed by more recent publications from the American Psychiatric Association17 (who note that off-­label prescribing should be reimbursed) and the Royal Australian and New Zealand College of Psychiatrists18 who emphasise shared decision-­making and the presumption of capacity. Examples of acceptable use of drugs outside their licences/labels Table 14.5 gives examples of common unlicensed uses of drugs in psychiatric practice. These examples would all fulfil the Bolam and Bolitho criteria in principle. An exhaustive list of unlicensed uses is impossible to prepare as the evidence base is constantly changing and because the expertise and experience of prescribers vary. A particular strategy may be justified in the hands of a specialist in psychopharmacology based in a tertiary referral centre but be much more difficult to justify if initiated by someone with a special interest in psychotherapy who rarely prescribes. Note that some drugs do not have a UK licence for any indication. Two commonly prescribed examples in psychiatric practice are immediate-­release formulations of melatonin (used to treat insomnia in children and adolescents) and pirenzepine (used to treat clozapine-­induced hypersalivation). Awareness of the evidence base and documentation of potential benefits, adverse effects and patient consent are especially important here. Table 14.5  Examples of common unlicensed uses of drugs in psychiatric practice. Drug/drug group Unlicensed use(s) Further information Second-­generation antipsychotics Psychotic illness other than schizophrenia Licensed indications vary markedly, and in most cases are unlikely to reflect real differences in efficacy between drugs. Clozapine Bipolar disorder Substantial evidence to support efficacy when standard treatments have failed to control symptoms Cyproheptadine Akathisia Some evidence to support efficacy in this distressing and difficult to treat adverse effect of antipsychotics Fluoxetine/sertraline Generalised anxiety disorder Substantial supporting evidence Ketamine (racemate) Refractory depression Substantial evidence with both racemate and S-­isomer Melatonin (circadin) Insomnia in children Licence covers adults >55 years only. Probably preferable to unlicensed formulations of melatonin. Naltrexone Self-­injurious behaviour in people with learning disabilities Limited evidence base Acceptable in specialist hands Sodium valproate Treatment and prophylaxis of bipolar disorder Established clinical practice Evidence from other valproate preparations 22 - References References 948 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 14 References EMC. Summary of Product Characteristics. 2024; http://www.medicines.org.uk/emc/. Baldwin D, et al. Efficacy of drug treatments for generalised anxiety disorder: systematic review and meta-­analysis. BMJ 2011; 342:d1199. Bolam v Friern Barnet Hospital Management Committee [1957] 1 WLR582. Bolitho v City and Hackney Health Authority [1997] 3 WLR1151. British and Irish Legal Information Institute. Montgomery (Appellant) v Lanarkshire Health Board (Respondent) (Scotland). 2015; http://www.bailii.org/uk/cases/UKSC/2015/11.html. General Medical Council. Good practice in prescribing and managing medicines and devices. 2021 (last checked September 2024); https://www.gmc-­uk.org/guidance/ethical_guidance/14316.asp. Buckman Co. v. Plaintiffs’ Legal Comm. 531 U.S. 341. 2001; https://www.law.cornell.edu/supct/html/98-­1768.ZO.html. FindLaw. Off-­label use promotion is protected free speech. 2019 (last accessed September 2024); https://www.findlaw.com/legalblogs/second-­ circuit/off-­label-­use-­promotion-­is-­protected-­free-­speech/. Vijay A, et al. Patterns and predictors of off-­label prescription of psychiatric drugs. PLoS One 2018; 13:e0198363. Leslie DL, et al. Off-­label use of antipsychotic medications in Medicaid. Am J Manag Care 2012; 18:e109–117. Ishtiak-­Ahmed K, et al. Treatment indications and potential off-­label use of antidepressants among older adults: a population-­based descriptive study in Denmark. Int J Geriatr Psychiatry 2022; 37:10.1002/gps.5841. Martínez CE, et  al. Antidepressant use and off-­label prescribing in primary care in Spain (2013-­2018). An Pediatr (Engl Ed) 2022; 97:237–246. Hefner G, et  al. Off-­label use of antidepressants, antipsychotics, and mood-­stabilizers in psychiatry. J Neural Transm (Vienna) 2022; 129:1353–1365. Epstein RS, et al. The many sides of off-­label prescribing. Clin Pharmacol Ther 2012; 91:755–758. Wong J, et al. Off-­label indications for antidepressants in primary care: descriptive study of prescriptions from an indication based electronic prescribing system. BMJ 2017; 356:j603. Royal College of Psychiatrists. Use of licensed medicines for unlicensed applications in psychiatric practice (2nd edition) (CR210 Dec 2017). 2017 (last accessed September 2024); https://www.rcpsych.ac.uk/improving-­care/campaigning-­for-­better-­mental-­health-­policy/college-­ reports/2017-­college-­reports/use-­of-­licensed-­medicines-­for-­unlicensed-­applications-­in-­psychiatric-­practice-­2nd-­edition-­cr210-­dec-­2017. American Psychiatric Association. APA official actions: position statement on off-­label treatments. 2021 (last accessed September 2024); https://www.psychiatry.org/getattachment/053eae03-­9e23-­422f-­ab75-­2ea052eb6c81/Position-­Off-­Label-­Treatments.pdf. Royal Australian New Zealand College of Psychiatrists (RANZCP). ‘Off-­label’ prescribing in psychiatry. Professional Practice Guideline 4. 2023 (last accessed September 2024); https://www.ranzcp.org/getmedia/edc66b1d-­005b-­411d-­b277-­5c7fddc71ba2/ppg-­4-­off-­label-­prescribing-­ december-­2023.pdf. 23 - The Mental Health Act in England and Wales The Mental Health Act in England and Wales Prescribing psychotropics CHAPTER 14 The Mental Health Act in England and Wales The 1983 Mental Health Act (MHA) as amended by the 2007 MHA is the legislation within England and Wales that provides the framework for detaining and treating people with mental disorder in hospital. It also allows for the supervision of people in the community. Mental health law as it pertains to other countries is not covered in this book. The guidance here provides a quick summary of the sections that prescribers are likely to come across in their day-­to-­day work (Box 14.2). It is not an exhaustive list. The Act has a statutory Code of Practice for practitioners and Chapter 25 of the Code provides detailed guidance on the treatment rules of the Act.1 The MHA can be accessed at www.legislation.gov.uk. The power to treat under S58 is only for treatment of mental disorder. Physical treatment (generally) is governed by the normal rules of consent or, if the person lacks capacity, the authority of the Mental Capacity Act. The Responsible Clinician (RC) is usually the patient’s consultant. For the first 3 months of detention, the RC may give medication with or without consent to a person under one of the detention sections named for the treatment of their mental disorder. Thereafter, the patient’s consent or a second opinion must be sought. The 3 months’ countdown starts when medication for mental disorder is first administered while the patient is detained. This includes a patient detained under S2 who is then, without a break, detained under S3. For practical purposes the 3-­month rule is usually calculated from the date of first detention. Box 14.2  Civil and forensic detention sections Section 2 Admission for assessment which lasts for up to 28 days Section 3 Admission for treatment which may last up to 6 months and is renewable Section 36 Remand to hospital for treatment Section 37 Hospital Order made by the courts (runs like an S3) Notional 37 Treat as if subject to S37. This term is used informally under a number of different circumstances. One example is where a patient was previously detained under S47/49 and their restriction order expires. Section 38 Interim Hospital Order Section 41 Restriction order: an order made by the Crown Court restricting discharge. Accompanies S37 and is written as S37/41. Section 47 Transfer to hospital of prisoners Section 49 A restriction order which usually accompanies S47 (written as S47/49) Section 48 Applies to un­sentenced prisoners in need of urgent treatment and is accompanied by S49 (written as S48/49) Section 58 Treatment requiring consent or a second opinion Please note in law it is the Responsible Clinician (RC) who is accountable for the operation of S58 24 - Completion of forms T2 and T3 Completion of forms T2 and T3 25 - Arranging and preparing for SOAD visits Arranging and preparing for SOAD visits 26 - Statutory consultees Statutory consultees 950 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 14 If a patient consents to treatment, the RC completes a form T2. If a patient has not given consent or has not got the capacity to consent, a Second Opinion Appointed Doctor (SOAD) is called. The SOAD then completes a form T3. A copy of the forms T2 and T3 should be kept with the patient’s medication chart as recommended in paragraph 25.75 of the Code of Practice.1 Completion of forms T2 and T3 The following should be stated on the forms: ■ ■The name of the drug or the class of drug. ■ ■If the class of drug is stated, the number of drugs allowed at any one time. ■ ■The route of administration. ■ ■The maximum dosage with reference to BNF guidance. For example: Antipsychotic,second generation 1 oral within B ( ) × NF maximum dose limits. For a patient who has capacity and is consenting to treatment and is only willing to take a particular drug, it is appropriate for the RC to write the name of the drug instead of the name of the class of drug on the T2. For example: Olanzapine tablets only(oral)within BNF maximum dose limits. Psychotropics not found in the BNF may be written on a T2 or T3  with their indication. For example: Melperone tablets oral up to a maximum of 25mg dai ( ) ly for the treatment of schizophrenia. Non-­psychotropics used for the treatment of mental disorder should be included on the T2 and T3, for example omega-­3 fatty acids (fish oils) in schizophrenia. Antimuscarinics used to treat hypersalivation and the extrapyramidal side effects of antipsychotics should be included too. Arranging and preparing for SOAD visits The Code of Practice 25.51 states: ‘Clinicians should consider seeking a review by a specialist mental health pharmacist before seeking a SOAD certificate, particularly if the patient’s medication regime is complex or unusual.’ Statutory consultees The SOAD should consult with two people before issuing a T3. One must be a nurse. The other must not be a nurse or a doctor. Both must have been involved with the patient’s treatment. These two people are known as statutory consultees. Mental health pharmacists can perform this role where they have been involved in any recent review of a patient’s medication. 27 - What is consent What is consent? 28 - What is capacity What is capacity? Prescribing psychotropics CHAPTER 14 The Code of Practice 25.56 states: Statutory consultees may expect to have a private discussion with the SOAD and to be listened to with consideration. Issues that the consultees may be asked about include, but are not limited to: ■ ■the proposed treatment and the patient’s ability to consent to it; ■ ■their understanding of the past and present views and wishes of the patient; ■ ■other treatment options and the way in which the decision on the treatment ­proposal was arrived at; ■ ■the patient’s progress and the views of the patient’s carers; and ■ ■where relevant, the implications of imposing treatment on a patient who does not want it and the reasons why the patient is refusing treatment. What is consent? The Code of Practice 24.34 defines consent as: … the voluntary and continuing permission of a patient to be given a particular treatment, based on a sufficient knowledge of the purpose, nature, likely effects and risks of that treatment, including the likelihood of its success and any alternatives to it. Permission given under any unfair or undue pressure is not consent. For a patient to consent formally they must have the ‘capacity’ to make a decision. What is capacity? The Mental Capacity Act 2005 states that: ■ ■People must be assumed to have capacity unless it is established that they lack capacity. ■ ■People are not to be treated as unable to make a decision unless all practicable steps to help them do so have been taken without success. ■ ■People are not to be treated as unable to make a decision merely because they make an unwise decision. A patient is deemed to lack capacity if they cannot: ■ ■Understand relevant information about the decision to be made; or ■ ■Retain that information in their mind; or ■ ■Use or weigh that information as part of the decision-­making process; or ■ ■Communicate their decision (by talking, using sign language or any other means). The patient needs to fail on only one of the four points above to be deemed not to have capacity. Capacity may change over time so reassessment is important. A person may lack capacity about one decision but not about another. 29 - Section 62 urgent treatment Section 62 urgent treatment 30 - Section 132 duty of managers of hospitals to Section 132 duty of managers of hospitals to give information to detained patients 31 - Electroconvulsive therapy (ECT) Electroconvulsive therapy (ECT) 952 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 14 Section 62 urgent treatment If after 3 months medication is needed urgently to treat a patient’s mental disorder and it is not covered by a T2 or T3, S62 may be applied. The Code of Practice 25.38 states: This applies only if the treatment in question is immediately necessary to: ■ ■save the patient’s life; ■ ■prevent a serious deterioration of the patient’s condition, and the treatment does not have unfavourable physical or psychological consequences which cannot be reversed; ■ ■alleviate serious suffering by the patient, and the treatment does not have unfavourable physical or psychological consequences which cannot be reversed and does not entail significant physical hazard; or ■ ■prevent patients behaving violently or being a danger to themselves or others, and the treatment represents the minimum interference necessary for that purpose, does not have unfavourable physical or psychological consequences which cannot be reversed and does not entail significant physical hazard. Each Trust should design a form for the clinician in charge of treatment (usually the consultant) to state what the treatment is, why it is immediately necessary and the length of treatment. Section 132 duty of managers of hospitals to give information to detained patients With regard to S132 and consent to treatment the Code of Practice 4.20 states: Patients must be told what the Act says about treatment for their mental disorder. In particular they must be told: ■ ■the circumstances (if any) in which they can be treated without their consent – and the circumstances in which they have the right to refuse treatment; ■ ■the role of second opinion appointed doctors (SOADs) and the circumstances in which they may be involved; and ■ ■(where relevant) the rules on electroconvulsive therapy (ECT) and medication administered as part of ECT. Electroconvulsive therapy (ECT) Section 58a deals with ECT. Treatment for ECT is authorised on forms: T4 For consenting adults 18 and over, may be written by the RC or SOAD T5 For consenting patients under 18, to be written by SOAD only T6 For patients who lack capacity, to be written by SOAD only 32 - Community patients Community patients 33 - Reference Reference Prescribing psychotropics CHAPTER 14 All patients under the age of 18 who are to receive ECT, whether or not they are detained under the MHA, must have treatment authorised on a T5 or T6. Patients who have the capacity to consent must not receive ECT unless they do consent (in emergencies this can, however, be over-­ridden under S62 of the Act). There is no 3-­month rule with regard to ECT and this also applies to medication given as part of ECT. Hence a form for ECT must always be in place regardless of the first date of detention. The forms should indicate the maximum number of treatments the patient is to receive (Code of Practice paragraph 25.23). Community patients Patients on a Community Treatment Order (CTO) should have treatment authorised on one of the following forms: CTO11 Written by SOAD, after 1 month on a CTO, when the patient lacks capacity CTO12 Written by the RC when the patient has capacity and is consenting to treatment, after 1 month on a CTO There is no legal authority to give patients medication in the community if they refuse it. Reference Gov.UK. Code of practice: Mental Health Act 1983. 2017 (last accessed August 2024); https://www.gov.uk/government/publications/ code-­of-­practice-­mental-­health-­act-­1983#history. 34 - Site of administration of intramuscular injec Site of administration of intramuscular injections 954 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 14 Site of administration of intramuscular injections Table 14.6 gives the sites of administration formally permitted in the individual product’s EU licence. Other routes and sites may be possible but pharmacokinetic analysis of administration via these sites is generally not available. Table 14.6  Sites of administration of intramuscular injections. Antipsychotic generic name and formulation Licensed site(s) of administration Typical antipsychotic (FGA) depots Bromperidol decanoate in sesame oil (available in Belgium, Germany, Italy, Luxembourg and the Netherlands1,2) Deep intramuscular injection into the gluteal muscle. SPCs in some countries recommend to alternate injections into the left and right sides to prevent pain at the injection site.3 Flupentixol decanoate in thin vegetable oil derived from coconuts Deep intramuscular injection into the upper outer buttock (dorsogluteal) or lateral thigh (vastus lateralis).4 As with all oil-­based injections it is important to ensure, by aspiration before injection, that inadvertent intravascular entry does not occur.5 This probably applies to dorsogluteal injections only; for all other sites where there are no major blood vessels close to the injection site, this is unnecessary.4 Fluphenazine decanoate in sesame oil Deep intramuscular injection into the gluteal region.4 Has also been administered into the lateral surface of the thigh muscle but this is unlicensed. Administration into the deltoid is not recommended by manufacturer.6 In the USA, licensed to be used ‘intramuscularly or subcutaneously’. The site of administration is not specified. Drug leakage appears to be lower after SC injection than after intramuscular administration.7 Fluspirilene in vegetable oil8 (available in some EU countries, Canada, Argentina and Israel9) Deep intramuscular injection into the gluteal muscle (intragluteal). Because of its microcrystalline form, irritation and inflammation symptoms may occur at the injection site. Manufacturer recommends to alternate between left and right gluteal muscles.3,10 Haloperidol decanoate in sesame oil Deep intramuscular injection into the gluteal region.4 It is recommended to alternate between the two gluteal muscles.11 As the administration of volumes greater than 3mL is uncomfortable for the patient, such large volumes are not recommended.11,12 Can also be administered into the deltoid muscle according to the manufacturer.13 Although this is an unlicensed use, one trial suggests it is safe and effective.14 Perphenazine decanoate in sesame oil (used in the Nordic countries, Belgium, Portugal and the Netherlands15) Deep intramuscular injection.15,16 No other information available. Table 14.6  (Continued ) Antipsychotic generic name and formulation Licensed site(s) of administration Perphenazine enanthate in sesame oil (in clinical use in the Nordic countries, Belgium, Portugal and the Netherlands15) Pipotiazine palmitate in sesame oil4 (variable availability) Zuclopenthixol decanoate in thin vegetable oil derived from coconuts Atypical antipsychotic (SGA) depots Gluteal muscle administration4 Aripiprazole Prefilled syringe for prolonged-­release suspension Aripiprazole lauroxil Prefilled syringe for extended-­release suspension Aripiprazole lauroxil nanocrystal dispersion Prefilled syringe for extended-­release suspension Olanzapine pamoate monohydrate Powder and vehicle for prolonged-­release suspension Paliperidone palmitate 1-­monthly Prolonged-­release suspension for injection every month Prescribing psychotropics Deep intramuscular injection into the gluteal region.15,17 Administration should be by deep intramuscular injection into the gluteal region.18 Deep intramuscular injection into the upper outer buttock (dorsogluteal) or lateral thigh (vastus lateralis).4 As with all oil-­based injections it is important to ensure, by aspiration before injection, that inadvertent intravascular entry does not occur.19 Gluteal injections should be alternated between the two gluteal muscles. Deltoid muscle administration4,20 Deltoid injections should be alternated between the two deltoid muscles.20 The powder and vehicle vials and the prefilled syringe are for single ­use only.4 Intramuscular administration into the deltoid or gluteal (441mg dose only) muscle.4,21 CHAPTER 14 Intramuscular injection into the deltoid or gluteal muscle.22 Not intended for repeat dosing. Given as a single dose to initiate treatment with aripiprazole lauroxil.22 Olanzapine pamoate monohydrate should only be administered by deep intramuscular gluteal injection by a healthcare professional trained in the appropriate injection technique and in locations where post-­injection observation and access to appropriate medical care in the case of overdose can be assured.23 Injected slowly, deep into the deltoid or dorsogluteal muscle (the two initial loading doses should be administered in the deltoid muscle so as to attain therapeutic concentrations rapidly).4,24 Following the second initiation dose, monthly maintenance doses can be administered in either the deltoid or gluteal muscle. Administration should be in a single injection. The dose should not be given in divided injections.24 (Continued ) 956 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 14 Table 14.6  (Continued ) Antipsychotic generic name and formulation Licensed site(s) of administration Paliperidone palmitate 3-­monthly Prolonged-­release suspension for injection every 3 months Deltoid muscle administration25 The specified needle for administration of Trevicta into the deltoid muscle is determined by the patient’s weight (see manufacturer’s advice). It should be administered into the centre of the deltoid muscle. Deltoid injections should be alternated between the two deltoid muscles. Gluteal muscle administration25 To be administered into the upper outer quadrant of the gluteal muscle. Gluteal injections should be alternated between the two gluteal muscles. Paliperidone palmitate 6-­monthly Prolonged-­release suspension for injection every 6 months Byannli is for gluteal intramuscular use only. It must not be administered by any other route. Each injection must be administered only by a healthcare professional giving the full dose in a single injection. It should be injected slowly, deep into the upper outer quadrant of the gluteal muscle. A switch between the two gluteal muscles should be considered for future injections in the event of injection site discomfort. Needles from the 3-­monthly or 1-­monthly paliperidone palmitate injectable pack or other commercially available needles must not be used when administering Byannli.26 Risperidone microspheres (Consta) Powder and vehicle for prolonged-­release suspension Following reconstitution, administer via deep intramuscular deltoid or gluteal injection.27 Risperidone ISM (Okedi) Powder and solvent for extended-­release suspension After reconstitution, administer by deep intramuscular deltoid or gluteal injection.28 Risperidone 2-­weekly injection (Rykindo) Prefilled syringe and powder vial for prolonged-­release suspension After reconstitution, administer via intramuscular injection into the gluteal muscle.29 Risperidone subcutaneous long-­acting injections (Perseris [RBP-­7000], Uzedy [TV-­46000]) Extended-­release suspension Subcutaneous administration in the abdomen or upper arm.30,31 Prior to administration of Perseris (RBP-­7000), the liquid and powder syringes need to be mixed by passing the contents back and forth between the syringes. Intramuscular injections for rapid tranquilisation Aripiprazole Solution for injection To enhance absorption and minimise variability, injection into the deltoid or deep within the gluteus maximus muscle, avoiding adipose regions, is recommended.32 Haloperidol Solution for injection Intramuscular administration.33 Preferably, the gluteal muscle is selected when the dosage volume is high. The deltoid muscle is preferred for low doses of the injection. However, there is no information on the dosage limit for these specific muscle groups. Choice of site is at the discretion of the prescriber according to the manufacturer.34 35 - References References Prescribing psychotropics CHAPTER 14 Table 14.6  (Continued ) Antipsychotic generic name and formulation Licensed site(s) of administration Lorazepam Solution for injection Intramuscular administration. Can be administered into the gluteal, deltoid or frontal thigh area according to the manufacturer.35 A 1:1 dilution of Ativan injection with normal saline or Sterile Water for Injection BP is recommended in order to facilitate intramuscular administration and absorption.18 Olanzapine Powder for solution for injection Inject slowly, deep into the muscle mass. The exact site of administration is not specified and choice of muscle site should be a clinical decision according to the manufacturer.36 Not to be used intravenously* or subcutaneously. Use the solution immediately within 1 hour of reconstitution.37 *Intravenous use has been reported38,39 but is off-­licence/label. Promethazine hydrochloride Solution for injection By deep intramuscular injection into a large muscle.40 Can be administered into the thigh, upper arm or gluteal region. Ensure muscle mass is sufficient for the volume being injected.6 Other intramuscular injections Clotiapine 40mg/4mL injection (available in Argentina, Belgium, Israel, Italy, Luxembourg, South Africa, Spain, Switzerland and Taiwan41) By intramuscular injection.41 No other information available. Clozapine intramuscular injection 25mg/mL (unlicensed)42,43 Only for deep intramuscular administration into the gluteal muscle. 25mg IM clozapine = 50mg oral. The maximum volume that can be injected into each site is 4mL (100mg). For doses greater than 100mg daily, the dose may be divided and administered into two sites. (Injection sites should be rotated as per usual IM practice.) Administration into the lateral thigh and deltoid muscles has been used in one case series.42 FGA, first-­generation antipsychotic; ISM, in situ microparticles; SC, subcutaneous; SGA, second-­generation antipsychotic; SPC, summary of product characteristics. References Purgato M, et al. Bromperidol decanoate (depot) for schizophrenia. Cochrane Database Syst Rev 2012; 11:CD001719. Riboldi I, et al. Practical guidance for the use of long-­acting injectable antipsychotics in the treatment of schizophrenia. Psychol Res Behav Manag 2022; 15:3915–3929. Eumedica. Medical Information Department – written communication, 2020. Janssen UK. Guidance on the Administration to Adults of Oil-Based Depot and Other Long-­Acting Intramuscular Antipsychotic Injections, 7th edn. 2022 (last accessed August 2024); https://www.hpft.nhs.uk/media/6180/guidance-­on-­im-­administration-­of-­oil-­based-­depots-­and-­ other-­long-­acting-­antipsychotic-­injections-­7th-­edition.pdf. Lundbeck Ltd. Summary of product characteristics. Depixol 20mg/ml solution for injection (flupentixol decanoate). 2021 (last accessed August 2024); https://www.medicines.org.uk/emc/product/995/smpc. Sanofi. Medical Information Department – verbal and written communication, 2017. Glazer WM, et  al. Injection site leakage of depot neuroleptics: intramuscular versus subcutaneous injection. J Clin Psychiatry 1987; 48:237–239. Spanarello S, et al. The pharmacokinetics of long-­acting antipsychotic medications. Curr Clin Pharmacol 2014; 9:310–317. Abhijnhan A, et al. Depot fluspirilene for schizophrenia. Cochrane Database Syst Rev 2007; 2007:CD001718. iMedikament.de. IMAP. 2024 (last accessed August 2024); https://imedikament.de/imap. 958 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 14 11. Essential Pharma Ltd. Medical Information Department – written communication, 2024. 12. Essential Pharma Ltd (Malta). Summary of product characteristics. HALDOL Decanoate (haloperidol decanoate) 100mg/ml solution for injection. 2023 (last checked August 2024); https://www.medicines.org.uk/emc/product/15246/smpc#gref. 13. Janssen. Medical Information Department – verbal and written communication, 2024. 14. McEvoy JP, et al. Effectiveness of paliperidone palmitate vs haloperidol decanoate for maintenance treatment of schizophrenia: a randomized clinical trial. JAMA 2014; 311:1978–1987. 15. Quraishi S, et al. Depot perphenazine decanoate and enanthate for schizophrenia. Cochrane Database Syst Rev 2000; 2:CD001717. 16. Laakeinfo.fi. PERATSIN DECANOATE solution for injection 108mg/ml (perphenazine decanoate). 2023 (last accessed August 2024); https://laakeinfo.fi/Medicine.aspx?m=2333. 17. Starmark JE, et  al. Abscesses following prolonged intramuscular administration of perphenazine enantate. Acta Psychiatr Scand 1980; 62:154–157. 18. myHealthbox 2012-­2024. Summary of Product Characteristics. 2024 (last accessed August 2024); https://myhealthbox.eu/en/. 19. Lundbeck Ltd. Summary of product characteristics. Clopixol 200mg/ml solution for injection (zuclopenthixol decanoate). 2022 (last accessed August 2024); https://www.medicines.org.uk/emc/product/6414/smpc. 20. Otsuka Pharmaceuticals (UK) Ltd. Summary of product characteristics. Abilify Maintena 300mg powder and solvent for prolonged-­release suspension for injection in pre-­filled syringe (aripiprazole). 2024 (last accessed August 2024); https://www.medicines.org.uk/emc/ product/12955/smpc%202022. 21. Alkermes Inc. Highlights of prescribing information. ARISTADA® (aripiprazole lauroxil) extended-­release injectable suspension for intramuscular use. 2018 (last accessed August 2024); https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/207533s013lbl.pdf. 22. Alkermes Inc. Highlights of prescribing information. ARISTADA INITIO® (aripiprazole lauroxil) extended-­release injectable suspension, for intramuscular use. 2023; https://www.aristada.com/downloadables/ARISTADA-­INITIO-­PI.pdf. 23. Eli Lily and Company Ltd. Summary of product characteristics. Zypadhera (olanzapine pamoate monohydrate) 210mg powder and solvent for prolonged release suspension for injection. 2023 (last assessed August 2024); https://www.medicines.org.uk/emc/product/6429/smpc. 24. Janssen-­Cilag Ltd. Summary of product characteristics. Xeplion (paliperidone) 25mg, 50mg, 75mg, 100mg, and 150mg prolonged-­release suspension for injection. 2023 (last accessed May 2024); https://www.medicines.org.uk/emc/product/7652/smpc. 25. Janssen-­Cilag Ltd. Summary of product characteristics. TREVICTA 175mg, 263mg, 350mg, 525mg prolonged release suspension for injection. 2023 (last accessed August 2024); https://www.medicines.org.uk/emc/medicine/32050. 26. Janssen-­Cilag Ltd. Summary of product characteristics. Byannli 700mg prolonged-­release suspension for injection in pre-­filled syringe (paliperidone). 2023 (last accessed August 2024); https://www.medicines.org.uk/emc/product/13307/smpc. 27. Janssen-­Cilag Ltd. Summary of product characteristics. RISPERDAL CONSTA 25mg powder and solvent for prolonged-­release suspension for intramuscular injection (risperidone). 2022 (last assessed August 2024); https://www.medicines.org.uk/emc/medicine/9939. 28. ROVI Biotech Ltd. Summary of product characteristics. Okedi (risperidone) 100mg powder and solvent for prolonged-­release suspension for injection pre-­filled syringes. 2023 (last accessed August 2024); https://www.medicines.org.uk/emc/product/13778/smpc. 29. Shandong Luye Pharmaceutical Co Ltd. Highlights of prescribing information. RYKINDO® (risperidone) for extended-­release injectable suspension for intramuscular use. 2023 (last checked June 2024); https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/212849s000lbl.pdf. 30. Indivior UK Ltd. Highlights of prescribing information. PERSERIS (risperidone) for extended-­release injectable suspension, for subcutaneous use. 2018 (last accessed September 2024); https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210655s000lbl.pdf. 31. Teva Neuroscience Inc. Highlights of prescribing information. UZEDY (risperidone) extended-­release injectable suspension for subcutaneous use. 2024 (last checked June 2024); https://www.uzedy.com/globalassets/uzedy/prescribing-­information.pdf. 32. Otsuka Pharmaceutical (UK) Ltd. Summary of product characteristics. Abilify 7.5mg/ml solution for injection (intramuscular) (aripiprazole). 2023 (last accessed August 2024); https://www.medicines.org.uk/emc/product/6239/smpc. 33. ADVANZ Pharma. Summary of product characteristics. Haloperidol injection BP 5mg/ml. 2024 (last accessed August 2024); https://www. medicines.org.uk/emc/product/514. 34. Concordia International. Medical Information Department – verbal and written communication, 2017. 35. Macure Pharma UK Ltd. Medical Information Department – written communication, 2024. 36. Lilly UK. Medical Information Department – verbal and written communication, 2017. 37. Eramol (UK) Ltd. Summary of product characteristics. Xyquila 10mg powder for solution for injection (olanzapine). 2023 (last accessed August 2024); https://www.medicines.org.uk/emc/product/15138/smpc. 38. Wang M, et al. A retrospective comparison of the effectiveness and safety of intravenous olanzapine versus intravenous haloperidol for agitation in adult intensive care unit patients. J Intensive Care Med 2022; 37:222–230. 39. Khorassani F, et  al. Intravenous olanzapine for the management of agitation: review of the literature. Ann Pharmacother 2019; 53:853–859. 40. Sanofi. Medical Information Department – written communication, 2024. 41. Carpenter S, et al. Clotiapine for acute psychotic illnesses. Cochrane Database Syst Rev 2004; 4:CD002304. 42. Henry R, et al. Evaluation of the effectiveness and acceptability of intramuscular clozapine injection: illustrative case series. BJPsych Bull 2020; 44:239–243. 43. Casetta C, et al. A retrospective study of intramuscular clozapine prescription for treatment initiation and maintenance in treatment-­resistant psychosis. Br J Psychiatry 2020; 217:506–513. The Maudsley® Prescribing Guidelines in Psychiatry, Fifteenth Edition. David M. Taylor, Thomas R. E. Barnes and Allan H. Young. © 2025 David M. Taylor. Published 2025 by John Wiley & Sons Ltd. Note: Page numbers in bold indicate tables and in italics indicate figures, where they fall outside the text range. 5a-­reductase inhibitors, psychiatric adverse effects  971 5HT see 5-­hydroxytryptamine 22q11.2 deletion syndrome (22q11.2DS)  820–­823 clinical features and risks  820 general prescribing principles  821 managing psychiatric disorders  821–­822 Abilify MyCite, adherence monitoring aid  933 Abnormal Involuntary Movement Scale  127 acamprosate, preventing relapse after alcohol detoxification  489–­490 ACE see angiotensin-­converting enzyme acetaldehyde, metabolism of alcohol  895 acetaminophen see paracetamol acetylcholinesterase inhibitors (AChE-­Is) Alzheimer’s disease  630, 632–­636, 642, 649 dementia with Lewy bodies  648 management of behavioural and psychological symptoms of dementia  671 mechanism of action  630, 631 mild cognitive impairment  648 older patients and dementia  654–­658, 659, 689 other dementias  647, 648, 649 rare dementias associated with neurological conditions  649 use in Parkinson’s disease  842 vascular dementia  647 activated partial thromboplastin time, psychotropic agent effects  965 activation adverse effects, depression in children and adolescents  571 Acuphase see zuclopenthixol acetate acute behavioural disturbance use of term  543 see also drug-­induced excited states acutely disturbed/violent behaviour  62–­73 oral/inhaled treatment  62 parenteral treatment  62–­65 practical measures  65 zuclopenthixol acetate  66–­67 acute mania, treatments  310–­315 AD see Alzheimer’s disease adapted Naranjo adverse drug reaction scale  972, 973 addiction  477–­560 see also alcohol dependence; dependence syndrome; drugs of misuse; illicit drugs; new psychoactive substances; nicotine dependence; opioid dependence; smoking; substance misuse and dependence ADH see alcohol dehydrogenase ADHD see attention deficit hyperactivity disorder adherence  927–­936 antipsychotics  30, 928–­929, 933–­934 assessing  929, 930 clinician-­patient relationship  939 definitions and terminology  927 enhancing medication adherence  931–­934 factors affecting  929 impacts of non-­adherence  928–­929 intervention  932 intervention research of poor quality  931 lithium  284 monitoring and assessing attitudes  931 object relations  939 rates and degrees  927–­928 relational aspects  939–­944 relational factors influencing clinicians  939 relational factors influencing patients  940 restarting medications after period of non-­compliance  937–­938 strategies  931 administration of medicines alternative routes  115–­118 covertly in food and drink, older people  629, 694–­699 covertly in food and drink for older people  629, 694–­699 site of intramuscular injections  954–­957 adolescents bulimia nervosa/binge eating disorder  794 see also children and adolescents adrenergic a2 agonists, tics and Tourette’s syndrome  615 ADRs see adverse drug reactions aducanumab, Alzheimer’s disease treatment  646 adverse drug reactions adapted Naranjo adverse drug reaction scale  972, 973 Naranjo scale  972, 973 adverse drug reactions (ADRs) anticholinergic effects of antipsychotics  43–­44 antipsychotics in menopausal women  859–­860 Index 976 Index adverse drug reactions (ADRs) (cont’d) biochemical effects of psychotropics  959, 960–­965 discussion with patients  941 haematological effects of psychotropics  959, 965–­966 increased incidence and severity in older people  627–­628 non-­psychotropics with psychiatric effects  969–­974 psychiatric adverse effects of non-­psychotropic drugs  969–­974 psychiatric effects of antiseizure medications  812–­813 psychotropic sensitivity in people with learning difficulties  825 see also extrapyramidal side effects AF see atrial fibrillation age effects changes in pharmacodynamics  627–­628 depression in children and adolescents  570 see also children and adolescents; older people aggressive behaviours Huntington’s disease  832 paradoxical/disinhibitory drug reactions, benzodiazepines  471–­473 valproate treatment  290 agitation and irritability, Huntington’s disease  832, 833 agomelatine in overdose  913 smokers  892 agonist replacement therapy, limited evidence for stimulant use disorder  532 agranulocytosis  245, 251, 267–­268, 275–­276, 959, 966 akathisia  43, 44, 127, 128, 131–­134 alanine aminotransferase (ALT)  960 albumin hepatic impairment  753, 754 psychotropic agent effects  960 alcohol dehydrogenase (ADH)  895, 896 alcohol dependence  479–­497 in children and adolescents  493 clinical assessment  479–­480 mild  480, 485 moderate  480, 485 in older people  493 pharmacologically assisted withdrawal  482–­487 in pregnancy  492–­493 preventing relapse after detoxification  489–­492 severe  480, 486 Wernicke’s encephalopathy/thiamine deficiency  487–­488 withdrawal  480–­489 alcohol detoxification benzodiazepines  484–­486 carbamazepine  487 community or in-­patient  482 fixed dose treatment regimen  485–­486 pharmacologically assisted withdrawal  482–­487 preventing relapse  489–­492 symptom-­triggered treatment regimen  486 alcohol use amnesia  898 ataxia  898 bariatric surgery effects  855 disulfiram reaction  490 driving impairment  922 electrolyte disturbances  898 health guidance  479 metabolism of  895 pharmacodynamic interactions  897–­899 pharmacokinetic interactions  895–­897 psychotropic drug combination  895–­899 sedation  897 alcohol use disorder (AUD) comorbid mental health disorders  494–­496 see also alcohol dependence Alcohol Use Disorders Identification Test (AUDIT)  480, 482 alcohol withdrawal  480–­489 benzodiazepines  484–­487 common interventions  484 community detoxification  482 delirium tremens  480, 481, 482, 486 mild  480, 484 pharmacologically assisted/ detoxification  482–­487 seizures  480, 481 severe  481, 484 severity assessment  480, 483 treating somatic symptoms  488–­489 treatment interventions  484 aldehyde dehydrogenase  895, 896 alkaline phosphatase in blood, psychotropic agent effects  960 allopurinol  226 α2A-­adrenoceptor agonists, see also guanfacine alpha blockers, older patients with urinary retention, drug safety  658 alpha-­lipoic acid, for antipsychotic-­induced weight gain  145 ALT see alanine aminotransferase alternative therapies Alzheimer’s disease management  641, 643–­645 inclusion on MHA forms T2 and T3  950 see also complementary therapies; natural remedies Alzheimer’s disease (AD) atrial fibrillation patients  847 cognitive enhancers  630–­641 adverse effects  635–­637 combination treatment  634 dosing and formulations  633–­634 drug interactions  637–­640 drug tolerability  634–­635 efficacy  632 mechanism of action  630 switching drugs  632–­633 differentiating from vascular dementia  647 management with alternative substances  641, 643–­645 NICE guidelines  642 novel antibody treatments  646–­647 amantadine for antipsychotic-­induced weight gain  145 for fatigue in multiple sclerosis  837 for tardive dyskinesia  136 ambivalence about medication, clinicians understanding patients  940–­941 amfebutamone see bupropion amfetamines attention deficit hyperactivity disorder in adults  798–­800 breastfeeding mothers  747 depression  388 in pregnancy  727 stimulant use disorder  533–­534 see also methamphetamine use disorder amino acids, for tardive dyskinesia  137 amisulpride  3, 4 clozapine augmentation  221 efficacy  3 in overdose  915 plasma level monitoring  869–­870 target range  868 use in patients with hepatic impairment  754, 756, 761 amitriptyline antidepressant  337 for clozapine-­induced hypersalivation  258, 259 post-­stroke pain treatment  393 in pregnancy  720 serotonin reuptake inhibition  404 ammonia in blood, psychotropic agent effects  960 amnesia, alcohol effects  898 amylase in blood, psychotropic agent effects  961 AN see anorexia nervosa Anafranil see clomipramine analgesics headache after ECT  384 managing behavioural and psychological symptoms of dementia  668 opioid avoidance for patients on naltrexone  490, 518 opioid substitution treatment combination  518–­519 safety in older patients/dementia  660–­661 see also non-­steroidal anti-­inflammatory drugs; opioids; paracetamol angiotensin-­converting enzyme (ACE) inhibitors, lithium interaction  284–­285 angiotensin II receptor antagonists, lithium interaction  285 anhedonia, stimulant use detoxification  535 ANI see asymptomatic neurocognitive impairment anorexia nervosa (AN)  792–­794 antidepressants  793 co-­morbid conditions  792, 794 monitoring when on oral electrolyte supplementation  794 NICE guidelines  795 psychological symptom treatment  793 relapse prevention  794 treating physical aspects  793–­794 weight restoration  792 Antabuse see disulfiram antiamyloid therapy, Alzheimer’s disease treatment  646–­647 antibiotics psychiatric adverse effects  969 safety in older patients/dementia  662 anticholinergic adverse effects of antipsychotics  43–­44 anticholinergic burden, cognitive impairment  642 anticoagulants, safety/use in older patients/ dementia  662 anticonvulsants benzodiazepine properties  484 borderline personality disorder  789 people with learning difficulties  827 use in alcohol withdrawal management  480, 481 see also antiseizure medications anti-­dementia drugs  630–­649 use in renal impairment  778 see also cognitive enhancers antidepressants adverse effects, relative and absolute risks  444–­445 with alcohol  899 anorexia nervosa  793 antipsychotic augmentation  35 with antipsychotics for psychotic depression  362 anxiety spectrum disorders  340 arrhythmia induction  411–­415 atrial fibrillation patients  846 bariatric surgery patients  850 bipolar depression  321 bleeding risks  432–­439 borderline personality disorder  789 breastfeeding mothers  735, 736, 737–­740 bulimia nervosa/binge eating disorder  794–­795 cardiac effects  406–­408, 409–­415 choice  338–­339 co-­prescribed with warfarin leading to non-­GI bleeding risk  433 diabetes mellitus  423–­425 dosing  626 increasing if insufficient response  345, 346 driving impairment  922 drug interactions  401–­405 pharmacodynamic effects  402, 404–­405 pharmacokinetic effects  401–­402, 403 duration of treatment  340 effectiveness  337 electroconvulsive therapy combination  384 Fatal Toxicity Index  412 glucose homeostasis effects  423–­425 hyperbolic tapering  366, 376, 379, 382 hyperprolactinaemia  420–­422 hyponatraemia induction  416–­419 ketamine  357 managing behavioural and psychological symptoms of dementia  672–­673 managing treatment-­resistant depression  348–­356, 357 minimum effective doses  342, 366 natural  440–­443 next-­steps if no response  340 onset of action  338 in overdose  913–­915 overview  337–­341 perioperative bleeding risks with non-­SSRI antidepressants  437 pharmacodynamic drug interactions  402, 404–­405 pharmacokinetic drug interactions  401–­402, 403 post-­stroke prophylaxis  393 practical application of tapering  380–­381 in pregnancy  719–­722 prolactin effects  420 prophylaxis  393, 397–­400 relapse risk of discontinuation after medium/long term use  398–­399 relative adverse effects  338–­339, 412 risks to people with epilepsy  815 St John’s wort  440–­443 sexual dysfunction  426–­431 smokers  893 stopping  378 sudden cardiac death  411, 412 suicidality  339 suicide risks in children and adolescents  570–­571 swapping and stopping guide  368–­371 switching  345, 366–­372 tapering  366, 376, 378–­382 Index target ranges  874 use in older people with depression  688–­693 use in patients with hepatic impairment  753, 757–­758, 761 use in patients with renal impairment  772–­775 use in stimulant use disorder  535 antidepressant withdrawal at risk patients  375 avoidance  375–­376 clinical relevance  375 incidence and severity of symptoms  373–­374 signs and symptoms  373–­376 stopping  378 switching  366–­367 time course  374 treatment  376 troubleshooting during tapering  381 antiemetics, safety in older patients/ dementia  658–­659 antihistamines driving impairment  923 safety in older patients/dementia  661, 674 antihypertensives, safety/use in older patients/dementia  661 anti-­inflammatory drugs, Alzheimer’s disease management  644–­645 antimalarials psychiatric adverse effects  969 QT prolongation  165 antiparkinsonian treatments, psychiatric adverse effects  970 antipsychotic depot, see also long-­acting injectable antipsychotics Antipsychotic Non-­Neurological Side-­Effects Rating Scale  4 antipsychotics adherence to treatment  30, 928–­929, 933–­934 administration of  115–­118 buccal  117 inhalation  115, 116 intranasal  115, 116–­117 intravenous  117 rectal  116, 118 sublingual  115, 117 transdermal  116 adverse effects  1, 2, 3–­4, 23–­24, 30, 43–­44, 126–­213 acute kidney injury risk  769 agranulocytosis  245, 251, 267–­268 akathisia  43, 44, 127, 128, 131–­134, 207 atrial fibrillation risk  846 blood pressure changes  182–­185 cardiomyopathy  254 cardiovascular adverse effects  253–­257 colitis  245 978 Index antipsychotics (cont’d) constipation  241, 263–­266 delirium  245 diabetes and impaired glucose tolerance  174–­181, 207 dyslipidaemia  207 dystonia  127, 128 ECG changes (QTc prolongation)  161–­168, 207 eosinophilia  245 extrapyramidal symptoms  126–­130, 207 gastrointestinal hypomotility  241, 263–­266 gastrointestinal necrosis  245 haematological adverse effects  251–­252 heat stroke  245 hepatic failure/enzyme abnormalities  245 hyperglycaemia  186 hyperlipidaemia  186 hyperprolactinaemia  190–­194, 196, 207 hypersalivation  241, 258–­262 hypertension  183–­184 hyponatraemia  186–­189 hypothermia  245 interstitial lung disease  245 interstitial nephritis  245 knee-­buckling  245 myocarditis  253–­254, 255 neuroleptic malignant syndrome  150–­153 neutropenia  267–­272 ocular effects  245 orthostatic hypotension  182–­183, 207 in overdose  913–­915 pancreatitis  246 parotid gland swelling  246 pericardial effusion  246 pericarditis  246 plasma lipids  169–­173 pneumonia  204–­206 polyserositis  246 pseudoparkinsonism  127–­128 QTc prolongation  161–­168, 207 renal injury risk  769 sedation  207 sexual dysfunction  195–­203, 207 skin reactions  246 stuttering  246 tardive dyskinesia  120, 127, 128, 135–­140, 208 thrombocytopenia  246 thromboembolism  211–­213, 246, 253 venous thromboembolism  211–­213, 253 weight gain  141–­149, 208 with alcohol  895–­899 antidepressant augmentation  35 with antidepressants for psychotic depression  362 augmentation of  58–­59 bariatric surgery patients  851–­852 bipolar disorder  300–­304, 305–­307, 310, 311 depression  301, 319 first generation  300 mania  300, 301, 302 second generation  300–­302 specific drugs  301–­302 borderline personality disorder  788 breastfeeding mothers  736, 741–­743 with caffeine  903 children and adolescents  590, 598, 606, 615–­616, 623, 626 choosing  2–­3 classification of  1–­2 clozapine augmentation  221 combinations of  7, 22–­25, 58–­59 discontinuation of  7, 28, 29, 30–­31, 119–­125 pattern of tapering  121–­122 reduction of olanzapine  121, 122 tapering in practice  122 when to attempt discontinuation  123 driving impairment  922 equivalent doses  14–­15 first-­generation adverse effects  3–­4, 49 classification  2 diabetes, antipsychotic-­related  174 equivalent doses  14 long-­acting injectable antipsychotics  75, 76 maximum doses  11, 12 minimum effective doses  8 nomenclature  49 penfluridol  106–­107 relative efficacy  3 role of older antipsychotics  49–­50 treatment algorithm  46 treatment of negative symptoms  35 hepatic impairment  754–­756, 761 high-­dose  55–­56 adverse effects  18, 76 efficacy  17–­18 prescribing and monitoring  17–­19 recommendations  19 Huntington’s chorea  831 increased free plasma levels in hepatic impairment  753–­754 long-­term treatment  8–­84 managing behavioural and psychological symptoms of dementia  668 maximum doses  11–­12 menopausal women  858, 859, 860 minimum effective doses  8 monitoring  40–­41 monotherapy poor response to  22 switching to  59 mortality risks in dementia patients  669 neurobiology of withdrawal  120 oestrogen interactions  858, 859, 860 optimal dosage  55 options for menopausal women  860 in overdose  915–­916 people with 22q11.2 deletion syndrome  822 people with epilepsy, risks  816 people with learning difficulties  826 plasma level variations  56–­57 polypharmacy  22–­25, 59, 95, 226 adverse effects  23–­24 long-­term treatment  22–­23 poor response to antipsychotic monotherapy  22 poor tolerability  207–­210 in pregnancy  715–­718 first-­generation  715–­716 neurodevelopment effects  717–­718 second-­generation  716–­717 preventing sudden cessation by non-­compliance  933 principles of prescribing  7 prophylaxis  28–­33 alternative views  31 discontinuation of  30–­31 dose for  30 reducing  28 relative adverse effects  43–­44 relative efficacy  3–­4 renal impairment  769–­771 response assessment  7 second-­generation  49, 50 adverse effects  3–­4 classification  2 diabetes, antipsychotic-­related  174–­176 equivalent doses  14, 15 long-­acting injectable antipsychotics  4, 75 maximum doses  11, 12 minimum effective doses  8 neuroleptic malignant syndrome association  151 optimal dosage  55 relative efficacy  3 treatment algorithm  46 treatment of negative symptoms  35 smokers  892–­893 stopping  7, 28, 30–­31, 90, 119–­125 hyperbolic reduction schedule  121, 122 pattern of tapering  121–­122 reduction of olanzapine  121, 122 tapering in practice  122 when to attempt discontinuation  123 withdrawal effects  119–­120, 123 suppositories  118 switching medication  57–­58, 207–­210 target ranges  868–­873, 873–­874 teratogenic potential  715–­717 topiramate  221, 228 use in patients with hepatic impairment  754–­756, 761 use patients with in renal impairment  769–­771 withdrawal effects  119–­120, 123 see also individual drug names antiretroviral therapy (ART) adverse psychiatric effects  808–­809 human immunodeficiency virus treatment  804 interactions with psychotropic drugs  804, 807–­808 pharmacokinetic interactions with other drugs  545 antiseizure medications  882 driving impairment  922 interactions with psychotropic drugs  813–­814 managing behavioural and psychological symptoms of dementia  673 psychiatric side-­effects (adverse and beneficial)  812–­813 use in alcohol dependence treatment  492 see also anticonvulsants; valproate antispasmodics, safety in older patients/ dementia  659 anxiety children and adolescents with autism spectrum disorder  610 comorbid alcohol use disorder  495 drug treatment in anorexia nervosa  793 Huntington’s disease  832, 833 menopausal women  858 in pregnancy  726–­727 anxiety spectrum disorders  446–­475 atrial fibrillation patients  847 benzodiazepines  446, 460 caffeine effects  905 children and adolescents  582–­586 after prescribing  584–­585 before prescribing  582–­583 clinical guidance  582 diagnostic issues  582 dosages  585 what to prescribe  583–­584 cognitive behavioural therapy  447, 448, 449 multiple sclerosis  836 NICE guidelines  448–­449 and nicotine  909 people living with human immunodeficiency virus  805–­806 pre-­school children  586 psychological approaches  448 specific drugs used  449–­455 SSRIs/SNRIs  446–­447 see also generalised anxiety disorder; obsessive-­compulsive disorder; panic disorder; post-­traumatic stress disorder; social phobia anxiolytic effect, benzodiazepines  460 anxiolytics driving impairment  922 use in renal impairment  776–­777 see also benzodiazepines apathy, Huntington’s disease  832, 833 apgar scores, medications in pregnancy  720, 723, 724 aripiprazole  8, 11, 15, 24, 43 for antipsychotic-­induced weight gain  145 Aristada  12, 88 bipolar disorders  301, 305, 306, 316 borderline personality disorder  788 cardiac safety of  164 clozapine augmentation  221 effects on impulse control disorders  560 hyperprolactinaemia  191 long-­acting injections  85–­89 bipolar disorder  305, 306 brands  88 delayed doses  86, 87 doses and frequencies  77, 85, 86, 87 switching to  86 in overdose  915 pharmacokinetics  81 plasma level monitoring  870 pneumonia association  204–­205 in pregnancy  717, 718 QTc prolongation  164 rapid-­cycling bipolar affective disorder  316 target range  868 weight restoration in anorexia nervosa  792 Aristada (aripiprazole lauroxil)  12, 88 arrhythmia cardiovascular risk factors  166 clozapine  240 flumazenil  70 induction by antidepressants  411–­415 physiological risk factors  164 psychotropic drug risks  845 ART see antiretroviral therapy ascites, risk in hepatic impairment  753, 754 ASD see autism spectrum disorder asenapine bipolar disorder  301 psychosis  8, 11, 12, 15, 43 sublingual  62, 117 aspartate aminotransferase (AST), psychotropic agent effects  961 aspirin, valproate interactions  292 assessing adherence  929, 930 AST see aspartate aminotransferase asymptomatic neurocognitive impairment (ANI), HIV related  806 ataxia, alcohol effects  898 atomoxetine, attention deficit hyperactivity disorder in adults  799, 801 atrial fibrillation (AF)  845–­848 Index psychiatric conditions increasing risk  846, 847 psychotropic drug prescription  845–­847 treatment  845 types  845 atropine  258, 259, 489, 660 attachment style of patients affecting relationship with clinician  941 attention deficit hyperactivity disorder (ADHD) in adults  798–­802 diagnosis  798 NICE guidelines  800 non-­stimulant medication  798, 799, psychostimulants  798, 799, 800 amfetamines  533 borderline personality disorder relationship  789 caffeine effects  905 children with 22q11.2 deletion syndrome  821 children and adolescents  562, 563, 574, 597–­604 bipolar disorder/bipolar affective disorder relationship  574 diagnostic issues  597 inattention, overactivity and impulsiveness symptoms in autism spectrum disorder  607–­608 melatonin use for insomnia  620–­621 prescribing guidelines  597–­598, 599–­602 drug use in renal impairment  778 medication risks in people with epilepsy  816–­817 and nicotine  909 in pregnancy  727 stimulant use disorder  533 atypical eating disorders  795 atypical/typical antipsychotic classification  1–­2 AUD see alcohol use disorder AUDIT see Alcohol Use Disorders Identification Test autism spectrum disorder (ASD) children and adolescents  605–­613, 620–­621 inattention, overactivity and impulsiveness symptoms  607–­608 melatonin use for insomnia  620–­621 pharmacological treatment of co-­ occurring disorders and problem behaviours  607–­610 pharmacological treatment of core symptoms  605–­606 restricted repetitive behaviours and interests  606 social and communication impairment  606 psychotropic drugs used  826–­827 980 Index baclofen, preventing relapse after alcohol detoxification  492 BALANCE study, bipolar disorder  290, 326 bariatric surgery  849–­856 drug pharmacokinetic alterations  849 general recommendations for psychotropic prescribing  854 lithium in perioperative phases  853 medication formulation considerations  849 mental health after surgery  855 psychiatric illness risk  849 Barnes Akathisia Rating Scale  127 basophils, psychotropic agent effects  965 Bazett’s correction formula  162 BDD see body dysmorphic disorder BED see binge eating disorder behavioural changes, benzodiazepine induced disinhibition  471–­473 behavioural disturbance see acutely disturbed/violent behaviour; aggressive behaviours; drug-­induced excited states behavioural and psychological symptoms of dementia (BPSD)  667–­679 non-­drug management measures  667–­668 pharmacological measures  668–­679 beneficial psychiatric effects, antiseizure medications  812–­813 benign ethnic neutropenia (BEN)  268, 269, benperidol  43 benzhexol (trihexyphenidyl), clozapine-­ induced hypersalivation  259 benzodiazepinea, breastfeeding  746 benzodiazepine dependence  464, 540–­542 dose reduction recommendations  540 novel illicit drugs  540 overuse of prescribed medication  540 polysubstance use  541, 542 withdrawal management  466–­469, 540–­542 benzodiazepines  64–­65 adverse effects  461–­462 adverse effects of long-­term use  464, 465 alcohol withdrawal treatment  484–­487 anxiolytic effect  460 breastfeeding mothers  746 with caffeine  903 for catatonia  154–­155 concentration in normal dosing and UK legal limit  923 dependence/withdrawal/ discontinuation  464–­465, 540–­542 diazepam equivalent doses  466, 467 direct taper or switch to diazepam  466 disinhibition  471–­473 driving impairment  922 drug interactions  462 fixed dose regimen for alcohol withdrawal  485–­486 hypnotic effect  460 long-­term use effects  464–­465 mania treatment in bipolar disorder  310, 311–­312 for neuroleptic malignant syndrome  151 not recommended for managing behavioural and psychological symptoms of dementia  671–­672 in overdose  917 pregnancy  541 process before tapering  468 psychiatric disorder treatment  460–­463 reduction schedules  469 sedatives in hepatic impairment  761 smokers  892 stopping  466 symptom-­triggered regimen for alcohol withdrawal  485, 486–­487 tapering  466 tapering patterns  467 tapering process  468 for tardive dyskinesia  136 troubleshooting during tapering process  468–­469 use in anxiety spectrum disorders  446 use in children and adolescents with autism spectrum disorder  609 use in depression  461 use in pregnancy  726 use in psychosis  461 withdrawal management  466–­469, 540–­542 symptoms  465 benztropine, clozapine-­induced hypersalivation  259 beta agonists, safety in older patients/ dementia/Parkinsons  659 betahistine, for antipsychotic-­induced weight gain  145 bethanechol, for constipation treatment  265 bicarbonate in blood, psychotropic agent effects  961 bilirubin in blood, psychotropic agent effects  961 binge eating disorder (BED)  794–­795 comorbid depression  795 NICE guidelines  795 biochemical effects of psychotropics  959, 960–­965 bipolar disorder/bipolar affective disorder  279–­334 antipsychotic drugs  300–­304, 311 long-­acting injections  305–­307 atrial fibrillation patients  846 carbamazepine  295–­299 children and adolescents  573–­579 after prescribing  574 attention deficit hyperactivity disorder relationship  574 before prescribing  573 clinical guidance  573–­574 depression treatments  577 first-­line treatments  577 mania treatments  575–­576, 577 specific issues  574–­575 what to prescribe  573, 575–­577 comorbid alcohol use disorder  495 depression  319–­325 antipsychotics  301, 302 lithium  280 meta-­analysis of drug studies  319 valproate  290 disruptive mood dysregulation disorder relationship  574 lithium  279–­288 maintenance treatment  280 prophylaxis  326, 327, 328 stopping/withdrawal effects  331–­332 tapering  332–­333 mania acute/hypomania  310–­315 antipsychotic treatments  300, 301, 302, 311 benzodiazepines  310, 311–­312 lithium treatment  279–­280 treatment strategies  310 valproate treatment  289–­290 multiple sclerosis  836 other treatments  574–­575 people living with human immunodeficiency virus  805 physical monitoring  283, 291, 297, 308–­309 postpartum psychosis risk  715 in pregnancy  722, 725–­726 prophylaxis  326–­330 antipsychotics  301, 302 carbamazepine  295–­296 lithium  326, 327, 328 valproate  290 rapid cycling type  290, 316–­318 relapse after stopping medication  332 stopping lithium and other mood stabilisers  331–­334 tapering lithium  332–­333 valproate  289–­294 bleeding gastrointestinal irritant drugs  753 SSRI effects  393–­394, 404, 409, 432–­439 warfarin interactions with SSRIs  846 see also platelets blonanserin  8, 12, 15, 43, 227 blood-­brain barrier, increased permeability with old age  628 blood clotting antipsychotics risk of pathological clotting  212 see also bleeding; platelets blood count, antipsychotic medication monitoring  40 blood lipids, antipsychotic medication monitoring  40 blood pressure changes  182–­185 antipsychotic medication monitoring  41 hypertension  41, 183–­184, 241 orthostatic hypotension  182–­183, 207 blood tests biochemical effects of psychotropics  959, 960–­965 haematological effects of psychotropics  959, 965–­966 blood transfusion in surgery, SSRI risks  436–­437 BN see bulimia nervosa body dysmorphic disorder (BDD)  587–­592 children and adolescents  587–­594 NICE guidelines  588–­589 psychological therapies  447, 587 SSRIs/SNRIs  447, 588 treatment duration and follow-­up  591 treatment initiation  589 treatment-­refractory cases  590 bone loss, anorexia nervosa risk  794 bone marrow suppression, antiretrovirals  807 bone mineral density (BMD), reduction by antiretrovirals  807 borderline personality disorder (BPD)  787–­791 antidepressants  789 antipsychotics  788 botulinum toxin  790 co-­morbid mental health conditions  787, 788 crisis management  790 drug treatment evidence  788–­790 ketamine  790 lack of evidence for drug treatments  787–­788 mood stabilisers and anticonvulsants  789 omega-­3 fatty acids  790 opioid antagonists  789 sedatives, short term use recommended  788 botulinum toxin borderline personality disorder  790 clozapine-­related hypersalivation  259 tardive dyskinesia  137 BPD see borderline personality disorder BPSD see behavioural and psychological symptoms of dementia bradykinesia  35 see also pseudoparkinsonism breast enlargement  196 breastfeeding antidepressants  735, 737–­740 antipsychotics  736, 741–­743 general prescribing principles  734–­735, 736 measuring infant exposure to drugs  734 mood stabilisers  736, 744–­745 not permitted with lithium use  736 stimulants  747 use of psychotropic medications  734–­747 bremelanotide use in patients with hepatic impairment  761 use in patients with renal impairment  778 brexanolone, in overdose  913 brexpiprazole  8, 12, 15, 43, 915 British Association for Psychopharmacology catatonia  156 dementia recommendations  649 bronchodilators, safety in older patients/ dementia  659–­660 buccal administration, antipsychotics  117 bulimia nervosa (BN)  794–­795 comorbid depression  795 NICE guidelines  795 buprenorphine analgesia for patients on opioid substitution treatment  519 blocking other opioids  506, 507, 519 cautions  513 conventional induction  508–­509 intoxication  513 liver function effects  513 low-­dose induction  509 methadone comparison  503 opioid substitution treatment  501, 503, 506–­514 overdose  513 prolonged-­release injection/ Buvidal  509–­510 timecourse of withdrawal symptoms  501 transferring back to methadone  512–­513 transition from methadone  510–­512 treatment methods and doses  508, 509 withdrawal  501, 516–­517 buprenorphine with naloxone (Suboxone)  513 bupropion (amfebutamone)  145, 259 adverse effects  527 attention deficit hyperactivity disorder in adults  799, 801 borderline personality disorder  789 clinical effectiveness  527 contraindicated in anorexia nervosa  794 nicotine addiction  527, 529 not recommended in bulimia nervosa/ binge eating disorder  795 in overdose  914 in pregnancy  721, 722 preparations and doses  527, 529 buspirone, in overdose  917 butyrophenones, in overdose  915 caffeine  901–­907 anxiety disorders  905 attention deficit hyperactivity disorder  905 Index dose and psychotropic effects of  902–­903, 902 drink types  901 energy drinks  901, 904 general effects of  902 interactions  903 intoxication  903–­904 mood disorders  905 pharmacokinetics  902–­903 schizophrenia  904 withdrawal effects  902 calcium antagonists, for tardive dyskinesia  137 calcium in blood, psychotropic agent effects  961 calcium levels, long-­term lithium use  282 cannabis/cannabinoids  36, 546, 550, 558, capacity and consent assessment in older people  694 covert administration of medicines in food and drink  629, 694–­699 learning difficulties  824–­825 Mental Health Act  629, 694–­698, 950, 951 right not to take medication  931 carbamazepine  295–­299 adverse effects  296–­297 bipolar disorder  295–­299, 310, 311 depression  295 discontinuation  297, 298 drug interactions  297–­298 formulations  295 indications  295–­296, 298 lithium interactions  286 mania  295 mechanism of action  295 in overdose  916 plasma levels  296 prescribing  298 pre-­treatment tests and monitoring  297, 298 prophylaxis  295–­296 smokers  892 target range  868 teratogenicity  297, 714, 723–­724 carbohydrate-­deficient transferrin (CDT), psychotropic agent effects  961 cardiac arrhythmia, atrial fibrillation  845–­848 cardiac death  161, 166 cardiac drugs, safety/use in older patients  662 cardiac effects antidepressants  406–­408, 409, 411–­412 drug-­induced excited states  543, 544 torsades de pointes/QT interval prolongation risk with methadone  506 cardiac malformation in infants, maternal mental health problems and lithium  723 982 Index cardiomyopathy  254 cardiovascular agents, psychiatric adverse effects  970 cardiovascular disease  169 cardiovascular effects, antiretrovirals  807 cardiovascular mortality  176 cardiovascular risks, acetylcholinesterase inhibitors in Alzheimer’s disease  637 care homes and environments, learning difficulties  825 cariprazine  8, 11, 15, 43 bipolar disorder  301, 321 in overdose  915 catatonia  154–­160 algorithm for treatment of catatonic stupor  157 associated psychiatric and medical conditions  154 ECT treatment  155 in schizophrenia  155 sub-­types  154 treatment  154–­156, 158 CATIE study  58 CBT see cognitive behavioural therapy CDT see carbohydrate-­deficient transferrin cerebrolysin, Alzheimer’s disease management  643–­644 cerebrovascular disease see vascular dementia cerebrovascular events anticoagulants reducing risks  662 antipsychotic risks  212, 669 see also stroke checklist for prescribing clinician factor  942–­943 patient/clinician relationship  943 patient factor  942 checklists, adherence assessment  931 chemotherapeutic agents, psychiatric adverse effects  971 chemotherapy, clozapine contraindicated  273–­274 child neurodevelopment, antipsychotic exposure during pregnancy  717–­718 children, 22q11.2 deletion syndrome  821 children and adolescents  561–­626 alcohol misuse  493 antipsychotics use  568, 573, 580, 590, 606, 615–­616 augmentation of other drug treatments  590 first-­generation antipsychotics  580, 615 rapid tranquillisation  623 second-­generation antipsychotics  568, 573, 580, 590, 608, 615–­616, 623 anxiety, with autism spectrum disorder  610 anxiety disorders  582–­586 chlorpromazine  1, 8, 11, 14, 28, 43, 118 chlorprothixene, possible teratogen  716 chocolate, Alzheimer’s disease management  644 cholesterol  169, 170, 962 cholinesterase inhibitors see acetylcholinesterase inhibitors chorea, Huntington’s disease  830, 831 chronic kidney disease (CKD), psychiatric disorders  769 Chronic Kidney Disease Epidemiology Collaboration (CKD-­EPI) formula, glomerular filtration rate estimation  766 cigarette smoking see smoking CIGH see clozapine-­induced GI hypomotility cimetidine, psychiatric adverse effects  971 citalopram as antidepressant  337, 338 binge eating disorder  794 switching antidepressants  366 use in patients with hepatic impairment  761 CK see plasma creatine kinase CKD see chronic kidney disease CKD-­EPI see Chronic Kidney Disease Epidemiology Collaboration Clinical Institute Withdrawal Assessment of Alcohol Scale -­ Revised (CIWA-­Ar)  482, 483, 484, 485, 486, 537 Clinical Opiate Withdrawal Scale (COWS)  501, 502 clinician-­patient relationship attachment style of patients  941 collaboration enhancing medication adherence  931 importance to outcomes  939 prescribing influences  943 clinicians responsibilities with ‘off-­label’ prescribing  945 seeking support  943 training in compliance therapy and adherence  933–­934 clomipramine (Anafranil) in pregnancy  719 serotonin reuptake inhibition  404 clonazepam, concentration in normal dosing and UK legal limit  923 clonidine, clozapine-­induced hypersalivation  259 clotiapine  8, 15, 957 clotting factor synthesis reduction, hepatic impairment  753 clozapine  214–­277 adverse effects  239, 241–­277 agranulocytosis  245, 251, 267–­268 cardiomyopathy  254 cardiovascular adverse effects  240, 253–­257 approved psychotropic medications  563–­564 attention deficit hyperactivity disorder  597–­604 medication continuing into adulthood  799 symptoms  562, 563, 574, 607–­608 autism spectrum disorder  605–­613, 620–­621 bipolar disorder  573–­579 body dysmorphic disorder  587–­594 bulimia nervosa/binge eating disorder  794 cognitive behavioural therapy  566–­567, 574, 587, 590, 595 depression  566–­572 with autism spectrum disorder  610 irritability (aggression, self-­injurious behaviour, and severe disruptive behaviours) in autism spectrum disorder  608 lack of engagement with psychological therapies  587 lithium plasma levels  281 melatonin use for sleep disturbance/ insomnia  575, 609–­610, 620–­622 obsessive compulsive disorder  587–­594 with autism spectrum disorder  610 optimising lithium treatment for prophylaxis in bipolar disorder  327 post-­traumatic stress disorder  595–­596 pre-­school children, anxiety disorders  586 prescribing principles  561–­565 psychosis  580–­581 psychotropic drug starting doses  626 rapid tranquillisation  623–­625 relative infant dose  734 restricted repetitive behaviours and interests, autism spectrum disorder  606 selective serotonin reuptake inhibitors  566–­567, 583–­584, 585, 588 sleep disturbance in autism spectrum disorder  609–­610 social and communication impairment, autism spectrum disorder  606 SSRI use  566–­567, 583–­584, 585, 588 suicidal ideation risk with SSRIs  588 symptom rating scales  573 tics and Tourette’s syndrome  614–­619 adrenergic a2 agonists  615 antipsychotics  615–­616 use of adult treatments  562 depression  568–­569 mania  574 obsessive compulsive disorder  592 chlordiazepoxide, alcohol withdrawal treatment  485–­486 chloride in blood, psychotropic agent effects  962 colitis  245 common adverse effects  241–­242 constipation  241, 263–­266, 882 delirium  245 eosinophilia  245 gastrointestinal hypomotility  263–­266 gastrointestinal necrosis  245 haematological adverse effects  251–­252 heat stroke  245 hepatic failure/enzyme abnormalities  245 hypersalivation  241, 258–­262 hypertension association  184, 241 hypothermia  245 interstitial nephritis  245 knee-­buckling  245 myocarditis  253–­254, 255 neutropenia  267–­272 nocturnal enuresis  242 ocular effects  245 pancreatitis  246 parotid gland swelling  246 pericardial effusion  246 pericarditis  246 pneumonia  242 pneumonia association  204, 205 polyserositis  246 sedation  242 seizures  242 skin reactions  246 stuttering  246 tachycardia  184, 234, 242, 253, 255 thrombocytopenia  246 thromboembolism  246, 253 uncommon adverse effects  245–­246 venous thromboembolism  253 weight gain  242 augmentation of treatment  220–­222 bipolar disorder  301–­302 borderline personality disorder  788 with caffeine  903 chemotherapy contraindication  273–­274 clozapine/norclozapine ratio  871 combined medications  24 community initiation  236–­240 adverse effects  239 dosing  237, 238 essential criteria for  236 initial work-­up  236–­237 mandatory blood monitoring and registration  237 recommended additional monitoring  239 relative contraindications  236 serious cardiac adverse effects  240 switching from other antipsychotics  239 titration schedules  238 delay/underuse of  57 dosing  214–­218, 237, 238 ECT augmentation  108–­109 EEG test  41 efficacy  3–­4 efficacy for negative symptoms  35 genetic testing for treatment  275–­277 agranulocytosis  275–­276 benign ethnic neutropenia  276 glucose tolerance impairment association  174–­175 hyponatraemia treatment  187 initiation schedules  214–­218 interruptions in treatment  234–­235 intramuscular clozapine  219 lithium use with  269–­270, 271 maximum dose  11 ‘off-­label’ prescribing  947 in overdose  915 people with 22q11.2 deletion syndrome  822 people living with human immunodeficiency virus and treatment-­resistant schizophrenia  804 plasma level monitoring  870–­871, 881–­882 plasma lipids, effect on  170 possible risks in pregnancy  717 prescribing of  7 relative efficacy  3 restarting after a break in treatment  234–­235 site of administration of intramuscular injections  957 smokers  892 smokers/non-­smokers, dosing regimens  216–­218 switching from other antipsychotics  239 target range  868 titration schedules  214–­215, 216–­218, 238 treatment optimisation  220–­225 treatment-­resistant schizophrenia  214–­233 alternatives to clozapine  226–­233 dosing regimen  214–­218 faster titrations  215 intramuscular clozapine  219 treatment optimisation  220–­225 clozapine-­induced GI hypomotility (CIGH)  263–­266, 882 clozapine rechallenge following severe constipation  265 management of suspected acute CIGH  264 prevention and simple management  264 risk factors  263 clozapine-­related life-­threatening agranulocytosis (CRLTA)  251 cocaine, stimulant use disorder  533 Cochrane review acute behavioural disturbance  63 benzodiazepines  64–­65 Index catatonia treatment  155 long-­acting injectable antipsychotics  74 smoking cessation  909 Cockroft and Gault equation, creatinine clearance calculation  766, 767 COCP see combined oral contraceptive pill cognitive behavioural therapy (CBT) anxiety spectrum disorders  447, 448, 449 benzodiazepine withdrawal  541, 542 children and adolescents  566–­567, 574, 587, 590, 595 psychosis  929 cognitive decline, anticholinergic drugs  654, 658 cognitive disturbances and decline, Huntington’s disease  834 cognitive enhancers adverse effects  631, 635–­637 Alzheimer’s disease  630–­641 combination treatment  634 discontinuation  640–­641 dose tolerability  634–­635 dosing and formulations  633–­634 drug interactions  637–­640 efficacy  632 managing behavioural and psychological symptoms of dementia  671 mechanism of action  630, 631 switching drugs  632–­633 see also acetylcholinesterase inhibitors; memantine cognitive impairment anticholinergic burden  642 multiple sclerosis  837 people living with human immunodeficiency virus  806 see also Alzheimer’s disease; dementia; mild cognitive impairment; vascular dementia collaboration between the patient and the prescriber, enhancing medication adherence  931 combination nicotine replacement therapy  524, 529–­530 combination therapies bipolar depression  319, 322 prophylaxis in bipolar disorder  327, 328 psychotic depression  362, 364 combined oral contraceptive pill (COCP), premenstrual syndrome  474–­475 communication, patient factor in prescribing  942 communication with patients, adherence relationship  933–­934 community detoxification, alcohol withdrawal  482 Community Treatment Order (CTO), Mental Health Act  953 complementary therapies, Parkinson’s disease  842 984 Index compliance use of term  927 see also adherence ‘compliance therapy’  933 compulsion, dependence syndrome  477–­478 concurrent illnesses, drug interactions in older people  627 consent see capacity and consent constipation causing drugs, avoid in hepatic impairment  754 constipation, clozapine-­induced  263–­266, clozapine rechallenge following severe constipation  265 prevention and management  241, 264 risk factors  263 controlled drugs psychostimulants used for attention deficit hyperactivity disorder in adults  798, 799 see also illicit drugs corticosteroids agents, psychiatric adverse effects  971 countertherapeutic use of medication  942 countertransference, clinicians  939, 942 covert administration of medicines in food and drink, older people  629, 694–­699 COVID-­19 pandemic  268 valproate preventative effects  290 COWS see Clinical Opiate Withdrawal Scale COX-­2 inhibitors, lithium interactions  285–­286 CrCl see creatinine clearance C-­reactive protein in blood, psychotropic agent effects  961 creatine kinase, psychotropic agent effects  962 creatine kinase (CK) elevations, antiretrovirals  807 creatinine in blood, psychotropic agent effects  962 creatinine clearance (CrCl), renal function assessment  766, 767 creatinine phosphokinase, antipsychotic medication monitoring  41 CRLTA see clozapine-­related life-­threatening agranulocytosis Crocus sativus (saffron), Alzheimer’s disease management  643 cross-­tapering, switching antidepressants  366 CTO see Community Treatment Order cultural beliefs, influencing adherence  940 CYP see cytochrome function cyproheptadine, ‘off-­label’ prescribing  947 cytisine adverse effects  526 clinical effectiveness for smoking cessation  526 nicotine addiction  526, 529 preparations and doses  526, 529 cytochrome (CYP) function  883–­891 alcohol and substrates for enzymes  896, 897, 898 antidepressant interactions with enzymes  339, 401, 401–­402, 403 caffeine metabolism/clearance  903 enzyme phenotype frequency by ancestry  889–­890 genetics  888–­891 nicotine/smoking effects  903, 910 environmental lithium effects  279 Huntington’s disease  834 inappropriate sexual behaviour  680–­687 Lewy bodies  630, 642, 648, 649, 842 management of behavioural and psychological symptoms of dementia  667–­679 mild cognitive impairment/pre-­clinical dementia  648 other kinds  648–­649 Parkinson’s disease  842 people living with human immunodeficiency virus  806 safer prescribing  654–­666 vascular  647 dementia with Lewy bodies (DLB)  630, 642, 648, 649, 842 dependence definition/diagnosis  477–­478 see also addiction; substance misuse and dependence dependence syndrome, definition  477–­478 depot antipsychotic medications  4, 29, 74–­80, 95 comparison of types  76 doses and frequencies  77–­78 improving adherence and outcomes  4, 29, 928–­929, 932–­933 pharmacokinetics  81 prescribing advice  75–­76 reduction of  123 restarting after period of non-­compliance  937 schizophrenia  29, 53 site of administration of intramuscular injections  954–­957 depression  335–­445 atrial fibrillation patients  846 basic prescribing principles  335–­336 children and adolescents  566–­572 acute phase  569–­570 after prescribing  569–­570 with autism spectrum disorder  610 before prescribing  567 clinical guidance  566–­571 diagnostic issues  566 discontinuation phase  570 maintenance phase  570 specific issues  570 what to prescribe  567–­569 chronic kidney disease  769 comorbid alcohol use disorder  494 comorbid with eating disorders  794, 795 diabetes mellitus association  423 drug treatment summary chart  344, 345–­347 Huntington’s disease  832, 833 ketamine as treatment  351, 357–­361 lithium DAI see Drug Attitude Inventory DAOAs see direct-­acting oral anticoagulants daridorexant in overdose  917 use in patients with hepatic impairment  761 use in patients with renal impairment  777 database studies, antidepressant associated hyponatraemia  416, 417 DBM see dibenzoylmethane DBS see deep brain stimulation DBT see dialectical behaviour therapy decision making, relational aspects  939–­943 deep brain stimulation (DBS)  137, 227, 230, 592 delirium  245 analgesics causing  660 antibiotics association  662, 663 anticholinergic drug effects  654, 658 antipsychotics used to manage  117, 118 benzodiazepine reactions similar to  471 caffeine at high doses  902 clozapine adverse effects  245 constipation effects in dementia patients  658 ECT/lithium effects  384, 385 excited delirium see drug-­induced excited states gamma-­butyrolactone withdrawal  534, 537 GHB/GBL withdrawal  534, 537 haloperidol treating in older people  706 hyperthermia and drug-­induced excited states  543 opioid effects  660 people living with human immunodeficiency virus  806 post-­injection delirium sedation syndrome  76, 77, 91 delirium tremens, severe alcohol withdrawal  480, 481, 482, 486 demeclocycline  187, 188 dementia  630–­653 Alzheimer’s disease  630–­647 antipsychotic prescriptions  119 drug recommendations and drugs to avoid  663–­664 augmentation of antidepressants in unipolar depression  280 prophylaxis of unipolar depression  281 managing behavioural and psychological symptoms of dementia  672–­673 menopausal women  858 multiple sclerosis  835 natural remedies St John’s wort  440–­443 taken without doctor’s knowledge  442 NICE guidelines  336 nicotine effects  909 older people  688–­693 Parkinson’s disease  840 people living with human immunodeficiency virus  804–­805 post stroke  393–­396 in pregnancy  719–­726 psychostimulants  388–­392 psychotic symptoms  362–­365 St John’s wort  440–­443 sexual dysfunction  426 stimulant use association  535 treatment resistant  348–­356 use of benzodiazepines  461 see also antidepressants; bipolar disorder designer drugs see new psychoactive substances; synthetic cannabinoids detoxification opioid substitution treatment  500 see also alcohol detoxification deutetrabenazine hepatic impairment  761 renal impairment  778 for tardive dyskinesia  136 dexamfetamine, attention deficit hyperactivity disorder in adults  798, 800 dextromethorphan, in overdose  914 DHA see docosahexanoic acid diabetes mellitus antidepressants  423–­425 antipsychotic-­related  174–­181 comorbid depression  423 see also glucose homeostasis dialectical behaviour therapy (DBT), borderline personality disorder  787 diazepam  68 with alcohol  898 benzodiazepine withdrawal  540, 541 concentration in normal dosing and UK legal limit  923 switching from benzodiazepines  466 diazepam equivalent doses, benzodiazepines  466, 467 dibenzoylmethane (DBM), Alzheimer’s disease management  645 DiGeorge syndrome (22q11.2 deletion syndrome)  820–­823 diphenhdyramine, clozapine-­induced hypersalivation  259 direct-­acting oral anticoagulants (DOACs) atrial fibrillation patients  845, 846 citalopram/escitalopram not affecting  394 possible SSRI interactions  394 renal function assessment  766 discontinuation symptoms when switching antidepressants  366–­367 see also withdrawal discontinuation syndrome, donepezil  632 disinhibition benzodiazepines  471–­473 clinical implications  472 incident rates  471 mechanism  472 risk factors  471–­472 subjective reports  472 see also paradoxical/disinhibitory/ aggressive drug reactions disruptive mood dysregulation disorder (DMDD), bipolar disorder relationship  574 distribution of drugs, changes with old age  628 disulfiram (Antabuse), preventing relapse after alcohol detoxification  491–­492 diuretics, lithium interaction  285 diversion and misuse of prescribed drugs opioids  503, 512, 513, 514 stimulants for ADHD in adults  798, 799 DLB see dementia with Lewy bodies DOACs see direct-­acting oral anticoagulants docosahexanoic acid (DHA) see omega-­3 fatty acids doctor see clinician donanemab, Alzheimer’s disease treatment  646 donepezil Alzheimer’s disease treatment  630–­637, 638, 640, 642 for tardive dyskinesia  137 dopamine and norepinephrine-­reuptake inhibitors see bupropion dopaminergic agents and dopamine partial agonists, possible effects on impulse control disorders  560 dosage reduction see tapering dose-­related adverse drug effects, increased in hepatic impairment  753 Driver and Vehicle Licensing Agency (DVLA), UK  923–­924 driving and psychotropic medicines  921–­926 duty of driver  923 duty of prescriber  924 effects of mental illness  921 medication-­induced sedation  923 Index psychotropic drug groups causing impairments  922 UK General Medical Council guidelines for prescribers  924 UK law  921–­923 driving restrictions, people with epilepsy  817 dronabinol, weight restoration in anorexia nervosa  792 droperidol  64, 65 drug administration see administration of medicines Drug Attitude Inventory (DAI)  931 drug half-­life  866 see also pharmacokinetics drug-­induced excited states  543–­544 hyperthermia risk  543, 544 identification  543 illicit drugs  543–­544 illicit and misused drugs  543–­544 management  543–­544 outcomes  544 pathophysiology  543 restraint risks  543 drug-­induced parkinsonism see pseudoparkinsonism drug interactions acetylcholinesterase inhibitors  637–­638, 638–­639 alternative treatments used by menopausal women  858 antidepressants  339, 401–­405 pharmacodynamic interactions  402, 404–­405 pharmacokinetic interactions  401–­402 atrial fibrillation patients  847 carbamazepine  297–­298 changes with old age  627, 628–­629 illicit drugs with prescribed psychotropic drugs  545, 546–­548 lithium  284–­286, 286 ACE inhibitors  284–­285 sodium levels  284–­285 memantine  637–­638, 640 post stroke depression  393 valproate  292 drugs of misuse summary  549–­553 see also diversion and misuse of prescribed drugs; illicit drugs; substance misuse and dependence dual diagnosis, substance misuse with mental illness  477 dual reuptake inhibitors adverse effects relative to other antidepressants  338 see also duloxetine; venlafaxine duloxetine borderline personality disorder  789 in overdose  914 in pregnancy  721 smokers  892 986 Index duty of managers of hospitals to give information to detained patients, S132 of the Mental Health Act dyslipidaemia  169 clinical management  170–­171 switching antipsychotics  207 dystonia extrapyramidal effects  127, 128 Huntington’s disease  830, 831 see also pseudoparkinsonism early-­onset schizophrenia spectrum (EOSS) disorder  580 eating disorders  792–­797 anorexia nervosa  792–­794 atypical/eating disorders not otherwise specified  795 bulimia nervosa/binge eating disorder  794–­795 comorbid depression  794, 795 NICE guidelines  795 Ebstein’s anomaly (cardiac malformation), lithium in pregnancy  723, 725 ECG changes, antiretrovirals  807 ECT see electroconvulsive therapy efavirenz, psychiatric adverse reactions  808 eGFR see estimated glomerular filtration rate eicosapentaenoic acid (EPA) see omega-­3 fatty acids elderly people atrial fibrillation  845–­848 genitourinary symptoms of menopause  861 optimising lithium treatment for prophylaxis in bipolar disorder  327 electrocardiogram (ECG) monitoring antipsychotic medication users  41, 165 methadone users with QT prolongation risk factors  506 see also QTc prolongation electroconvulsive therapy (ECT)  108–­110, 227 adverse effects  109 for catatonia  155 children and adolescents  568, 569 drug resistant depression treatment  351 managing behavioural and psychological symptoms of dementia  675 in pregnancy  722 psychotic depression treatment  363 psychotropic drug combination  384–­386 S58a of the Mental Health Act  952–­953 for treatment-­resistant schizophrenia  108–­109 electrolytes alcohol effects  898 anorexia nervosa  793–­794 antipsychotic medication monitoring  40 see also sodium levels electronic nicotine vaping devices see nicotine vaping devices embolic events, SSRIs decreasing risk  433 emergency situations, rapid tranquilisation  68–­69 energy drinks, caffeine content  901, 904 environmental lithium, high levels inversely related to suicide and dementia at a population level  279 eosinophilia  245 eosinophils, psychotropic agent effects  965 EOSS see early-­onset schizophrenia spectrum disorder EPA see eicosapentaenoic acid epilepsy  811–­819 learning difficulties comorbidity  825 psychiatric comorbidities  811–­812 see also people with epilepsy EPSEs see extrapyramidal side effects EPS (extrapyramidal symptoms) see extrapyramidal side effects erectile dysfunction  199, 200 erythrocyte sedimentation rate, psychotropic agent effects  966 escitalopram smokers  893 use in patients with hepatic impairment  761 esketamine, enantiomer of ketamine  357 esketamine (intranasal) treatment resistant depression  336, 351, 357, 359 see also ketamine Espranor orodispersible buprenorphine brand  507, 508 estimated glomerular filtration rate (eGFR), renal impairment assessment  766 ethanol see alcohol excited delirium use of term  543 see also drug-­induced excited states excretion of drugs, changes with old age  628 excretory capacity of the kidney, estimation in renal impairment assessment  766 expectations of treatment, placebo and nocebo effects  941 extended release (ER) preparations intramuscular injections  955, 956 memantine for older adults  633 extended release preparations, see also long-­acting injectable antipsychotics; modified-­release preparations; prolonged release injections; slow-­release oral morphine extrapyramidal side effects (EPSEs)  1–­2, 3, 126–­130 amisulpride  869 children  623 features of most common symptoms  127–­128 first generation antipsychotics  580 high-­dose antipsychotics  56 methamphetamine use plus antipsychotics  534 patient sensitivity  75 people with learning difficulties  825 people living with human immunodeficiency virus  804, 806 smoking alleviating symptoms  909 switching antipsychotics  207 treatment  128 see also pseudoparkinsonism family, improving medication adherence  932, 933 fasting plasma glucose (FPG) test  176, 177 Fatal Toxicity Index (FTI), antidepressants  412 fatigue multiple sclerosis  837 psychostimulants to reduce in depression  388, 389 fentanyl dependence, buprenorphine low-­dose induction  509 ferritin in blood, psychotropic agent effects  962 FGAs see first-­generation antipsychotics financial incentives, improving adherence  933 first-­generation antipsychotics (FGAs) adverse effects  3–­4, 49 bipolar disorder  300 children and adolescents  580 classification of  2 equivalent doses  14 impaired glucose tolerance and diabetes  174 long-­acting injectable antipsychotics  75, 76 maximum doses  11, 12 minimum effective doses  8 nomenclature  49 penfluridol  106–­107 people with learning difficulties  826 in pregnancy  715–­716 relative efficacy  3 role of older antipsychotics  49–­50 site of administration of intramuscular injections  954–­955 treatment algorithm  46 treatment of negative symptoms  35 fish oils dyslipidaemia treatment  171 mild/moderate depressions in older adults  689 schizophrenia treatment/ prevention  111–­114 for tardive dyskinesia  137 see also omega-­3 fatty acids fixed-­dose regimens, benzodiazepines for alcohol withdrawal management  485 fluid restriction, hyponatraemia treatment  187, 188 flumazenil, guidelines for use of  70 flunitrazepam, concentration in normal dosing and UK legal limit  923 fluoxetine bipolar depression  322 borderline personality disorder  789 bulimia nervosa  794 children and adolescents autism spectrum disorder  610 depression/bipolar disorder  566–­568, 569, 570–­571, 574 ‘off-­label’ prescribing  947 in pregnancy  720 suicidality in children and adolescents  566, 570–­571, 588, 610 flupentixol bipolar disorder  305, 306 borderline personality disorder  789 long-­acting injection doses and frequencies  77 pharmacokinetics  81 fluphenazine, smokers  893 fluvoxamine for antipsychotic-­induced weight gain  145 smokers  893 for tardive dyskinesia  137 folic acid, Alzheimer’s disease management  643 forms T2 and T3, Mental Health Act  950 forms T4/T5/T6, Mental Health Act  952–­953 formulations of drugs impaired absorption following bariatric surgery  849 problems with tablets when tapering  382 FPG see fasting plasma glucose test FRAMES principles (feedback, responsibility, advice, menu, empathy, self-­efficacy), NICE public health guidance on harmful drinking  479 frontotemporal dementias  648–­649 FTI see Fatal Toxicity Index full blood count, antipsychotic medication monitoring  40 galantamine Alzheimer’s disease  630–­636, 639, 642 mild cognitive impairment  636 gambling disorder  560 gamma-­aminobutyric acid A (GABA-­A)  897 gamma-­butyrolactone (GBL; pro-­drug of GHB)  537–­539 see also gamma-­hydroxybutyrate and gamma-­butyrolactone gamma-­glutamyl transferase (GGT), psychotropic agent effects  963 gamma-­hydroxybutyrate (GHB) and gamma-­butyrolactone dependence  537–­539 planned elective withdrawal  538–­539 unplanned withdrawal  538 withdrawal management  537–­539 withdrawal syndrome  534, 537 GASS see Glasgow Antipsychotic Side-­effect Scale gastro-­esophageal reflux disease (GERD) 22q11.2 deletion syndrome  820 clozapine  241 gastrointestinal bleeding, SSRI risks  433–­434 gastrointestinal disorders, drug safety in older patients/dementia  658–­659 gastrointestinal disturbances, antiretrovirals  807 gastrointestinal hypomotility, clozapine-­induced  263–­266 gastrointestinal irritant drugs, increased risk of bleeding in hepatic impairment  753 gastrointestinal necrosis  245 GBL see gamma-­butyrolactone G-­CSF see granulocyte-­colony stimulating factor generalised anxiety disorder (GAD) NICE guidelines  448 pregabalin  447–­448 specific drugs used  449–­450 SSRIs/SNRIs  446 valproate treatment  290 generalised seizures, severe alcohol withdrawal  480, 481 General Medical Council, UK, guidelines for prescribers, medical conditions and safe driving  924 genetics of cytochrome function  888–­891 genetic testing, for clozapine treatment  275–­277 genitourinary symptoms of menopause (GSM)  857, 861, 862 gestational diabetes, antipsychotics risk  716–­717 GFR see glomerular filtration rate GGT see gamma-­glutamyl transferase GHB see gamma-­hydroxybutyrate Ginkgo biloba  136, 222, 227, 641, 643 G see gamma-­hydroxybutyrate and gamma-­butyrolactone GABA-­A see gamma-­aminobutyric acid A gabapentin borderline personality disorder  789 tardive dyskinesia  137 use in patients with hepatic impairment  761 gabapentinoids (GABA analogues), addiction/physical dependence and withdrawal  464, 465, 469 GAD see generalised anxiety disorder galactorrhoea  196 Index ginseng, Alzheimer’s disease management  643 Glasgow Antipsychotic Side-­effect Scale (GASS)  4 glomerular filtration rate (GFR), estimation for renal impairment assessment  766 glucocorticoid receptor blocking, psychotic depression treatment  364 glucose in blood, psychotropic agent effects  963 glucose homeostasis antidepressant effects  423–­425 SSRIs improving control  423 see also diabetes mellitus glucose tolerance impairment, antipsychotic-­ related  174–­181, 207 glutamate, role in cognitive function/ dementia  630, 631, 672 glycated haemoglobin (HbA1c)  53, 175, 176, 177, 424, 432, 963 glycopyrrolate, clozapine-­induced hypersalivation  259 gonadotrophin-­releasing hormone agonists, medical menopause induction test  475 granulocyte-­colony stimulating factor (G-­CSF)  270–­271 GSM see genitourinary symptoms of menopause guanfacine attention deficit hyperactivity disorder in adults  799, 801 clozapine-­induced hypersalivation  259 gynaecological and obstetric haemorrhage, SSRI risks  435–­436 H2 see histamine-­2 HAD see HIV-­associated dementia haematological effects of psychotropics  959, 965–­966 haemodialysis, depression treatment  769 haemoglobin, psychotropic agent effects  966 half-­life of drugs  866 see also pharmacokinetics haloperidol  8, 11, 14, 43, 49, 50 acute behavioural disturbance  62, 63, 65 clozapine augmentation  221 intravenous administration  117 long-­acting injections, doses and frequencies  77 pharmacokinetics  81 possible teratogen  716 smokers  893 haloperidol decanoate  11, 14 Hamilton Depression Rating Scale (HAM-­D), drug effect assessment  337, 345 HAND see HIV-­associated neurocognitive disorders HbA1c see glycated haemoglobin 988 Index HD see Huntington’s disease HDL see high-­density lipoprotein cholesterol heat stroke  245 hepatic CYP enzymes antidepressant interactions  401–­402, 403 see also cytochrome function hepatic damage clozapine induced  245 hepatitis B and C infection effects  545 toxicity assessment in new drugs  762 valproate induced  291 hepatic encephalopathy, from reduced drug metabolism in hepatic impairment  753, 754 hepatic impairment in patients  753–­767 antidepressants  753, 757–­758, 761 antipsychotics  754–­756, 761 lower starting doses recommended  753–­754 mood stabilisers  759, 761 sedatives  754, 760, 761 stimulants  760 hepatitis B and C infections, drug metabolism effects  545 hepatotoxicity assessment in new drugs  762 avoiding known drugs in hepatically impaired patients  754 herbal medicine see natural remedies high-­density lipoprotein (HDL) cholesterol  169 high-­dose antipsychotics  17 adverse effects  18 efficacy  17–­18 recommendations  19 highly protein-­bound drugs, increased toxicity in hepatic impairment  753–­754 hirudin, Alzheimer’s disease management  643 histamine-­2 (H2) antagonists, safety in older patients/dementia  662 HIV, see also human immunodeficiency virus; people living with human immunodeficiency virus HIV-­associated dementia (HAD)  806 HIV-­associated neurocognitive disorders (HAND)  806 HIV mania, secondary mania in people living with human immunodeficiency virus  805 hormonal treatments, premenstrual syndrome  474–­475 hormone replacement therapy (HRT)  861–­863 adverse effect management  863 depression/anxiety treatment for menopausal women  858 local treatments for GSM  861, 862 products and regimens  861, 862, 863 risks  861 starting treatment  863 versus raloxifene for psychosis treatment in menopausal women  860 hospital managers, duty to give information to detained patients under S132 of the Mental Health Act  952 HRT see hormone replacement therapy 5HT6 receptor antagonist, Alzheimer’s disease management  644 human immunodeficiency virus (HIV)  803–­810 treatment advances  804 see also people living with human immunodeficiency virus Huntington’s disease (HD)  830–­834 cognitive symptoms  834 general principles of pharmacological symptom management  830–­831 mental and behavioural symptoms  831–­833 motor symptoms  830–­831 huperzine A, Alzheimer’s disease management  643 hyperbolic tapering antidepressants  366, 376, 379, 382 benzodiazepine  467 lithium for bipolar disorder  333 hypercalcaemia, lithium  282 hypercholesterolaemia  170 hyperglycaemia  174, 186 hyperlipidaemia  170, 171, 186 hyperparathyroidism, lithium  282 hyperprolactinaemia  2, 24, 41, 50, 190–­194, 196 antidepressants  420–­422 contraindications  191 effects of antipsychotic medication on prolactin concentration  190 management  191, 192 switching antipsychotics  207 hypersalivation  258–­262 clozapine  241 oral anticholinergic agents, safety in older patients/dementia  660 treatment  258, 259–­260 hypersensitivity reactions, drug-­induced hepatic damage  762 hypertension  41, 183–­184, 241 hyperthermia, drug-­induced excited states  543, 544 hypertriglyceridemia  169, 171 hypnotic effect, benzodiazepines  460 hypnotics breastfeeding mothers  736, 746 driving impairment  922 in pregnancy  727 use in renal impairment  776–­777 hypoalbuminaemia, hepatic impairment  753, 754 hypoglycaemia  898 hypokalaemia, anorexia nervosa  793–­794 hypokinetic phase/rigidity, Huntington’s disease  830, 831 hypomania, treatments  310–­315 hyponatraemia  186–­189 antidepressants  416–­419 lithium retention and toxicity  286 other psychoactive prescribed drugs  418 and syndrome of inappropriate antidiuretic hormone  186, 188 treatment  187–­188 and water intoxication  186 hypo-­oestrogenic states, high prolactin levels in menopausal women  860 hypophosphataemia, anorexia nervosa  794 hypotension  41, 43, 44 clozapine  241 orthostatic  182–­183, 207 hypothermia  245 hypothyroidism, lithium risk  282 Hy’s rule, assessment of hepatotoxicity of new drugs  762 iatrogenic dependence, benzodiazepines/ z-­drugs/gabapentinoids  464, 540 idalopirdine (5HT6 receptor antagonist), Alzheimer’s disease management  644 ideational perseveration, Huntington’s disease  832 illicit drugs drug-­induced excited state  543–­544 drugs of misuse summary  549–­553 interactions with prescribed psychotropic drugs  545–­548, 546–­548 see also new psychoactive substances; substance misuse and dependence iloperidone  8, 12, 15, 43, 915 IM see intramuscular... immediate-­release (IR) preparations attention deficit hyperactivity disorder treatments  600, 620, 799, 800 medication doses for older adults  633, 700 modified release stimulant preparations preferred in adults  799 impulsive behaviour, disinhibitory drug reactions, benzodiazepines  471–­473 inappropriate sexual behaviour in older people  680–­687 incongruence of affect, multiple sclerosis  836 infant exposure relative infant dose  734 see also breastfeeding inhaled administration acutely disturbed/violent patients  62 antipsychotics  62, 115, 116 injectable diamorphine, prescribing guidelines for opioid dependency  514 injections site of administration of intramuscular injections  954–­958 see also long-­acting injectable antipsychotics in-­patient detoxification, alcohol withdrawal  482 INR see international normalised ratio in situ microparticle technology see risperidone ISM insomnia melatonin use in children and adolescents  575, 609–­610, 620–­622 menopausal women  858 people living with human immunodeficiency virus  805, 808, in pregnancy  726–­727 see also sleep disturbance integrase strand transfer inhibitors, psychiatric adverse reactions  809 intentional non-­adherence  932 interferons-­α and -­β, psychiatric adverse effects  971 international normalised ratio (INR), psychotropic agent effects  967 interstitial lung disease  245 interstitial nephritis  245 intracranial/intracerebral haemorrhage, SSRI risks  434–­435 intramuscular (IM) injections, acute behavioural disturbance  62–­66 intranasal antipsychotics  115, 116–­117 intranasal esketamine, treatment resistant depression  336, 351, 357, 359 intranasal ipratropium, clozapine-­induced hypersalivation  259 intranasal naloxone  499 involuntary movements, abnormal see tardive dyskinesia ipratropium nasal spray, clozapine-­induced hypersalivation  259 IR see immediate-­release preparations irritability (aggression, self-­injurious behaviour, and severe disruptive behaviours), children and adolescents with autism spectrum disorder  608 irritability and agitation, Huntington’s disease  832, 833 isotretinoin, psychiatric adverse effects  971 racemic mixture  357 route of administration  357–­358 treatment resistant depression  351, 357–­361 see also esketamine ketoacidosis, diabetic  174, 175 kidneys see chronic kidney disease; renal... knee-­buckling  245 lactate in blood, psychotropic agent effects  963 LAI see long-­acting injectable antipsychotics lamotrigine borderline personality disorder  789 clozapine augmentation  221 life-­threatening cutaneous reactions  937 in overdose  916 restarting after period of non-­ compliance  937, 938 target range  868 laxative misuse/abuse  792, 961, 962 laxatives  239, 241, 264–­265, 658, 882 LDL see low-­density lipoprotein cholesterol learning difficulties  824–­829 capacity and consent  824–­825 epilepsy comorbidity  825 general considerations  824 prescribing practice  824–­825 lecanemab, Alzheimer’s disease treatment  646 legal issues Mental Health Act England and Wales (1983)  949–­953 ‘off label’ prescribing  945–­946 UK drug-­driving law  921–­923 see also capacity and consent lemborexant managing sleep disturbance in dementia  674 in overdose  917 use in patients with hepatic impairment  761 leukopenia, psychotropic agent effects  966 levetiracetam, for tardive dyskinesia  137 Levodopa, hypokinetic rigidity in Huntington’s disease  831 levomepromazine  11, 43 Lewy body dementia  630, 642, 648, 649, LFTs see liver function tests libido  196, 199 linaclotide, for constipation treatment  265 lipids see plasma lipids lipoproteins in blood, psychotropic agent effects  963 liraglutide, for antipsychotic-­induced weight gain  145 lisdexamfetamine attention deficit hyperactivity disorder in adults  798–­800 borderline personality disorder  789 bulimia nervosa/binge eating disorder  795 KarXT (xanomeline-­trospium), Alzheimer’s disease management  645 ketamine  65, 68, 357–­361 anti-­suicidal effects  339 bipolar depression  321 borderline personality disorder  790 dosing recommendations  358 mechanism of antidepressant action  357 ‘off-­label’ prescribing  947 in overdose  914 psychotic depression treatment  363 Index lithium  279–­288 adherence/non-­compliance limiting effectiveness  284 adverse effects  282–­283 with alcohol  899 augmentation of antidepressants in unipolar depression  280 bariatric surgery patients  852, 853 bipolar disorder  279–­288 depression  280 mania  279–­280, 310, 311 stopping treatment  331–­334 suicide risk  281 borderline personality disorder  789 with caffeine  903 clinical indications  279–­281, 284 clozapine use with  269–­270, 271 depression treatment  280–­281 discontinuation  283–­284 driving impairment  922 drug interactions  283, 284–­286 environmental concentration inversely related to suicide and dementia at a population level  279 formulations  282 mania, acute treatment  279–­280, 310, 311 mechanism of action  279 on-­treatment monitoring  283, 284 optimising treatment for different ages  327 in overdose  916 patients on long-­term lithium  280 people with learning difficulties  people living with human immunodeficiency virus  805 plasma levels  281 postpartum  736 in pregnancy  723, 725 pre-­treatment tests  283 prophylaxis for unipolar depression  281, 399 renal effects  282, 285 renal function assessment  766 target range  868 teratogenicity  283 thyroid effects  282 toxicity  282–­283 use in patients with hepatic impairment  754, 759, 761 withdrawal effects  331–­332 liver function tests (LFTs) interpretation  753, 762 monitoring to access drug effects  41, 754, 762 see also hepatic damage lofepramine, in overdose  914 lofexidine, clozapine-­induced hypersalivation  259 lone atrial fibrillation  845 990 Index long-­acting injectable (LAI) antipsychotics  4, 7, 23, 29, 74–­80 advice on prescribing  75–­76 aripiprazole  85–­89 for bipolar disorder  83–­84, 300, 301, 302, 305–­306, 326–­327 clozapine augmentation  221 differences between  76 doses and frequencies  77–­78 equivalent doses  14, 15 management of patients  83–­84 maximum doses  11, 12 for menopausal women  859 olanzapine  90–­92 paliperidone palmitate  93–­98 risperidone  94, 99–­105 test doses  75 long-­acting oral antipsychotics improving adherence  933 preventing sudden cessation  932–­933 restarting after period of non-­compliance  937 loop diuretics, lithium interaction  285 loperamides, safety in older patients/ dementia  658 lorazepam  68, 155 catatonia treatment  155 concentration in normal dosing and UK legal limit  923 rapid tranquillisation of children and adolescents  623 use in patients with hepatic impairment  761 low-­density lipoprotein (LDL) cholesterol  169 low-­dose aspirin co-­prescribed with SSRIs, GI bleeding risk  433, 434 loxapine  43, 893 lumateperone  8, 12, 15, 43, 208, 915 lung disease, interstitial  245 lurasidone  8, 11, 15, 43 bipolar depression  302 cardiac safety of  164 clozapine augmentation  221 in overdose  916 QTc prolongation  164 lymphocytes, psychotropic agent effects  966 MADRS see Montgomery-­Asberg Depression Rating Scale maintenance for drug dependence, opioid substitution treatment  500, 501–­504 maintenance phase, children and adolescents with depression  570 maintenance treatment bipolar disorder  326–­330 psychotic depression  363–­364 schizophrenia  29, 53 major depressive disorder (MDD)  335–­361 bipolar depression comparison  319 older people  688 see also depression malabsorptive surgical procedures, bariatric surgery  849 mania people living with human immunodeficiency virus  805 treatment in children and adolescents  575–­576 mania (bipolar disorder) antipsychotics  300, 301, 302, 311 benzodiazepines  310, 311–­312 carbamazepine  295 lithium treatment  279–­280 treatment options  310–­315 valproate treatment  289–­290 manic switch, depression in children and adolescents  571 MAOIs see monoamine oxidase inhibitors MARS see Medication Adherence Rating Scale MCI see mild cognitive impairment MDD see major depressive disorder MDRD see Modification of Diet in Renal Disease mean cell haemoglobin concentration, psychotropic agent effects  966 medical foods, Alzheimer’s disease management  644 medical menopause, assessing premenstrual syndrome/premenstrual dysphoric disorder  475 Medication Adherence Rating Scale (MARS)  931 medication-­taking aids  932 melatonin adverse effects, children and adolescents  621 for antipsychotic-­induced weight gain  146 children and adolescents  620, 621, 626 description  620 efficacy  620 managing behavioural and psychological symptoms of dementia  674 ‘off-­label’ prescribing  947 sleep disturbance/insomnia treatment, children and adolescents  575, 609–­610, 620–­622, 626 for tardive dyskinesia  137 melperone  15 memantine  222, 227 Alzheimer’s disease  630–­634, 636–­637, 640, 641 borderline personality disorder  789 immediate release versus extended release  633 managing behavioural and psychological symptoms of dementia  671 methods of action in AD treatment  630, 631 vascular dementia  647 memory, clinicians’ procedural memory and unconscious influences  939 menopause  857–­864 depression/anxiety  858 diagnosis  857 elderly care  861 genitourinary symptoms and treatments  857, 861, 862 hormone replacement therapy  861–­863 increased adiposity effects  859–­860 psychological symptoms  857, 858–­860 psychosis  858–­860 mental capacity see capacity and consent Mental Health Act (MHA), England and Wales (1983)  629, 682, 694–­698, 949–­953 mephedrone, misuse and dependence  533, 537, 543 metabolic abnormalities, antiretrovirals  808 metformin for antipsychotic-­induced weight gain  146 possible mood improvement in type II diabetes  424 methadone buprenorphine comparison  503 cautions  505–­506 general hospital settings  504, 505 hepatic/renal dysfunction  505 initiation of treatment  504 intoxication  505 opioid substitution treatment  501, 503–­506 in overdose  506, 917 psychiatric hospital settings  504–­505 titration schedules  504, 505 transferring back from buprenorphine  512–­513 transition to buprenorphine  510–­512 withdrawal  516 methamphetamine use disorder  533–­534 detoxification  534 psychotic symptoms  534–­535 methylphenidate attention deficit hyperactivity disorder in adults  798–­800 borderline personality disorder  789 driving impairment  922 people with learning difficulties  827 in pregnancy  727 psychotic depression treatment  364 metreleptin, weight restoration in anorexia nervosa  792 MHA see Mental Health Act (MHA) MI see myocardial infarction mianserin, in overdose  914 microdeletion syndrome, 22q11.2 deletion syndrome  820–­823 midazolam  64, 65 mild alcohol withdrawal  480 mild cognitive impairment (MCI), treatments  636, 643, 646, 648 mild neurocognitive disorder (MND), HIV related  806 mineral supplements anorexia nervosa  793 see also nutritional supplements minimum effective doses antidepressants  342, 366 antipsychotics  8 determining for patient  84 minocycline  226, 227 mirtazapine in overdose  914 in pregnancy  721–­722 smokers  893 weight restoration in anorexia nervosa  792 missed doses of psychotropic medication  937 MND see mild neurocognitive disorder moclobemide  914 modafinil for antipsychotic-­induced weight gain  146 depression  388 fatigue in multiple sclerosis  837 not recommended in pregnancy  727 in overdose  917 Modification of Diet in Renal Disease (MDRD) formula, glomerular filtration rate estimation  766 modified-­release (MR) preparations methylphenidate  600 stimulants for attention deficit hyperactivity disorder in adults  798, 799, 800 see also extended release preparations; slow-­release oral morphine molindone  12, 15 monoamine oxidase inhibitors (MAOIs) adverse effects, relative to other antidepressants  338 with alcohol  899 with caffeine  903 electroconvulsive therapy combination  385 glucose homeostasis  423, 424 hyponatraemia  416, 417, 418 interaction with tyramine-­containing foods  338–­339 not recommended for people living with human immunodeficiency virus  805 not recommended in pregnancy  722 in overdose  914 pharmacodynamic drug interactions  404–­405 serotonin syndrome  367 swapping and stopping antidepressants  368 monoclonal antibodies, Alzheimer’s disease treatment  646 monocytes, psychotropic agent effects  966 montelukast, psychiatric adverse effects  971 Montgomery-­Asberg Depression Rating Scale (MADRS), drug effect assessment  345 Montgomery vs Lanarkshire Health Board appeal case decision, ‘off-­label’ prescribing  945 mood disorders caffeine effects  905 see also bipolar disorder; depression mood elevation, psychostimulants use in depression  388 mood stabilisers adverse effects, rationale for reducing/ stopping  331 with alcohol  899 bariatric surgery patients  852 bipolar depression  319 bipolar disorder  279–­299, 310–­311 stopping treatment  331–­334 borderline personality disorder  789 breastfeeding mothers  736, 744–­745 combinations for rapid-­cycling bipolar affective disorder  316 managing behavioural and psychological symptoms of dementia  673 non-­antipsychotic agents for bipolar illness in pregnancy  723–­725 in overdose  916–­917 use in patients with hepatic impairment  759, 761 use in renal impairment  775–­776 withdrawal effects  331–­332 see also carbamazepine; lithium; valproate mood-­stabilising anticonvulsants, chronic kidney disease risk  769 mortality antipsychotic polypharmacy versus monotherapy  22, 23 antipsychotics versus other risk factors  166 cardiovascular with antipsychotics  18, 166, 176 diabetes-­related with antipsychotics  174 drug-­induced hyperthermia  544 neuroleptic malignant syndrome  151 motivation of patients adherence  929, 932, 933 readiness to change  940 movement disorders, and nicotine  910 MR see modified-­release MS see multiple sclerosis multiple sclerosis (MS)  835–­839 anxiety  836 bipolar disorder  836 cognitive impairment  837 depression  835 fatigue  837 Index pseudobulbar affect  836 psychosis  836–­837 multisubstance misuse see polysubstance abuse muscle rigidity see pseudoparkinsonism muscular spasm, uncontrolled see dystonia mutual aid and peer support, stimulant abstinence  532 myasthenia gravis, acetylcholinesterase inhibitors use in older patients/ dementia  660 myocardial function effects, drug-­induced excited states  543 myocardial infarction (MI), SSRI protective effects  433 myocarditis  253–­254, 255 myoclonus clozapine  241, 871 Huntington’s disease  831 lithium  269 nalmefene, alcohol dependence  490–­491 naloxone buprenorphine combination (Suboxone)  513 injection or internasal treatment  499 opioid overdose treatment  499 naltrexone for antipsychotic-­induced weight gain  146 borderline personality disorder  789 gambling disorder  560 ‘off-­label’ prescribing  947 people with learning difficulties  827 preventing relapse after alcohol detoxification  490 preventing relapse after opioid detoxification  517–­518 for tardive dyskinesia  137 NAPLS see North American Prodromal Longitudinal Studies Naranjo adverse drug reaction scale (adapted)  972, 973 National Confidential Inquiry into Suicide and Homicide by People with Mental Illness  928 National Institute for Health and Care Excellence (NICE) guidelines anxiety spectrum disorders  448–­449 attention deficit hyperactivity disorder in adults  800 attention deficit hyperactivity disorder in children and adolescents  599 borderline personality disorder  788 dementia  642 depression  336 eating disorders  795 generalised anxiety disorder  448 hypercholesterolaemia  170 obsessive compulsive disorder  449 panic disorder  448 prophylaxis in bipolar disorder  327 992 Index National Institute for Health and Care Excellence (NICE) guidelines (cont’d) psychotic disorder monitoring  176 relapse prevention after alcohol detoxification  489, 490, 492 schizophrenia  2, 52–­54 National Poisons Information Service (NPIS)  538 natural remedies Alzheimer’s disease management  641, 643 drug interactions in menopausal women  858 Ginkgo biloba  136, 222, 227, 641, 643 non-­standardised preparations  440, 441 potential risks  442 St John’s wort  440–­443 taken without doctor’s knowledge  442 nausea, clozapine  241 NbN see Neuroscience-­based Nomenclature NE see norepinephrine negative predictive value (NPV)  275 neonatal problems first-­generation antipsychotics risk  716 tricyclic antidepressant withdrawal  720 nephritis, interstitial  245 nephrotoxic drugs, renal function assessment  766 Netherlands Clozapine Collaboration Group  267 NEURAPRO trial  111–­112 neurocognitive disorders HIV related  806 inappropriate sexual behaviour in older people  680–­687 see also dementia neurodevelopment, antipsychotic exposure during pregnancy  717–­718 neuroleptic malignant syndrome (NMS)  150–­153 catatonic stupor in  155, 156 renal impairment  769 restarting antipsychotics  150 risk factors  150, 151 signs and symptoms  150 treatment  150, 151 neurological conditions, rare dementias  649 neuromodulation stimulant use disorder  533 see also transcranial magnetic stimulation Neuroscience-­based Nomenclature (NbN)  2, 49 neurotoxicity, lithium  283 neutropenia agranulocytosis  267–­268 benign ethnic neutropenia  268, 269 clozapine-­related  251, 267–­272 granulocyte-­colony stimulating factor  270–­271 lithium  269–­270 neutrophils, psychotropic agent effects  966 new psychoactive substances (NPSs/designer drugs)  477, 540, 543, 544 NICE see National Institute for Health and Care Excellence nicotine  908–­911 attention deficit hyperactivity disorder  909 depression and anxiety  909 drug interactions  910 movement disorders  910 Parkinson’s disease  910 psychotropic effects  908 schizophrenia  908–­909 smoking cessation and withdrawal symptoms  910 see also smoking nicotine dependence  523–­531, 910 bupropion  527, 529 cytisine  526, 529 electronic vaping devices  527–­528, 530 nicotine replacement therapy  523–­524, treatment algorithms  528–­530 varenicline  524–­526 withdrawal symptoms  910 nicotine replacement therapy (NRT)  523–­524 adverse effects  524 clinical effectiveness  524 combination of formulations  524, 529–­530 preparations and doses  525, 529–­530 nicotine vaping devices (vaping)  527–­528, 530 adverse effects  528 clinical effectiveness  528 preparations and doses  528, 530 N-­methyl-­D-­aspartate (NMDA) receptor antagonists Alzheimer’s disease  630 see also ketamine NMS see neuroleptic malignant syndrome nocebo effects, patient expectations of treatment  941 nocturnal enuresis, management  242 non-­adherence impacts  928–­929 lithium  284 rates and degrees of adherence  927–­928 restarting psychotropic medications after period of non-­compliance  937–­938 non-­competitive N-­methyl-­D-­aspartate receptor antagonists  630 non-­compliance see non-­adherence non-­iatrogenic benzodiazepine dependence  540 non-­nucleoside reverse transcriptase inhibitors  808–­809 non-­steroidal anti-­inflammatory drugs (NSAIDs) Alzheimer’s disease management  644–­645 co-­prescribed with SSRIs, GI bleeding risk  433, 434 lithium interactions  285–­286 safety in older patients/dementia  660 norclozapine  871 norepinephrine (NE)-­modulating agents see viloxazine norepinephrine (NE)-­reuptake inhibitors see atomoxetine; bupropion North American Prodromal Longitudinal Studies (NAPLS)  112 NPIS see National Poisons Information Service NPSs see new psychoactive substances NPV see negative predictive value NRT see nicotine replacement therapy NSAIDs see non-­steroidal anti-­inflammatory drugs nucleoside reverse transcriptase inhibitors, psychiatric adverse reactions  808 nutritional supplements Alzheimer’s disease management  643, 644 anorexia nervosa  793–­794 fatigue in multiple sclerosis  837 obesity  145, 145–­146, 166, 169, 176, 580, see also weight gain Objective Opiate Withdrawal Scale (OOWS)  501 object relations  939 obsessive compulsive behaviours, Huntington’s disease  832, 833 obsessive compulsive disorder (OCD) alternative and experimental treatments  591 children and adolescents  587–­594 with autism spectrum disorder  610 clinical guidance  587, 588–­589 need for drug treatment  587 psychological therapies  587 SSRI use  588 NICE guidelines  449, 588–­589 specific drugs used  453–­454 SSRIs/SNRIs  447 treatment duration and follow-­up  591 treatment initiation  589 treatment-­refractory cases  590 use of adult treatments  592 obstetric and gynaecological haemorrhage, SSRI risks  435–­436 OCD see obsessive compulsive disorder ocular effects, and antipsychotics  245 oesophageal varices, consequences of reduced hepatic blood flow  753 oestrogen antipsychotics effects  858 decline in menopausal women  857, 858, 860 selective oestrogen receptor modulators  860 oestrogen augmentation psychosis treatment adjunct for menopausal women  860 see also hormone replacement therapy ‘off-­label’ prescribing (outside a drug’s licensed indications)  945–­948 legal issues  945–­946 recommendations  946–­947 OGTT see oral glucose tolerance tests Okedi see risperidone ISM olanzapine acute behavioural disturbance  62, 63 acute kidney injury risk  769 bipolar depression  322 bipolar disorder  302, 310 borderline personality disorder  788 children and adolescents, adverse effects  573, 574 dose reductions  121, 122 doses and frequencies  77, 90 efficacy  3 glucose tolerance impairment association  175 linear dose reductions  121 long-­acting injections  90–­92 in overdose  916 pharmacokinetics  81 plasma level monitoring  871–­872 plasma lipids, effect on  169–­170 post-­injection delirium sedation syndrome  91 rapid-­cycling bipolar affective disorder  316 risks in pregnancy  716, 717 smokers  893 stopping  90 suppositories  118 target range  869 weight restoration in anorexia nervosa  792 olanzapine/fluoxetine combination, children and adolescents with bipolar depression  574, 577 olanzapine pamoate  11, 15 olanzapine/samidorphan combination, bipolar disorder  302 older people  627–­712 Alzheimer’s disease  630–­647 behavioural and psychological symptoms of dementia management  667–­679 covert administration of medicines in food and drink  629, 694–­699 dementia  630–­687 depression  688–­693 dose recommendations for common psychotropics  700–­712 general prescribing principles  627–­629 inappropriate sexual behaviour  680–­687 safer prescribing/cognitive risks  654–­666 omega-­3 (polyunsaturated) fatty acids (fish oils or supplements) Alzheimer’s disease management  643 borderline personality disorder  790 dyslipidaemia treatment  171 mild/moderate depressions in older adults  689 schizophrenia treatment and prevention  111–­114, 221 tardive dyskinesia  137 ondansetron  137, 226, 228 OOWS see Objective Opiate Withdrawal Scale opioid antagonists, borderline personality disorder  789 opioid dependence  498–­522 changes in prescribing practice  498 overdoes  498–­499 prescribing psychotropic medications  515 timecourse of withdrawal symptoms  501 opioid receptor agonists, buprenorphine blocking other opioids  506, 507 opioids detoxification and reduction regimens  516–­518 diversion potential of prescribed substances  503, 512, 513, 514 driving impairment  922 misuse  498–­522 overdose risk after detoxification  518 overdose symptoms and treatment  498–­499 psychiatric adverse effects  969 relapse prevention with naltrexone  517–­518 safe storage importance  505 safety in older patients/ dementia  660–­661 transferring from prescription drugs to buprenorphine  512 opioid substitution treatment (OST)  500–­519 alternative oral preparations  514 induction and stabilisation of maintenance treatment  501 injectable diamorphine  514 pain control in patients  518–­519 relapse prevention with naltrexone  517–­518 safe prescribing  501 slow-­release oral morphine  514 see also buprenorphine; methadone opioid withdrawal buprenorphine  516–­517 community settings  516–­517 methadone  516 specialist addiction in-­patient settings  517 timecourse of symptoms  501 treatment of symptoms  515 validated scales  501 Index oral glucose tolerance tests (OGTT)  176, 177 oral nicotine products see nicotine replacement therapy orexin antagonists see lemborexant; suvorexant orlistat for antipsychotic-­induced weight gain  146 for constipation treatment  265 orodispersible drug administration, Espranor/buprenorphine  507–­508 orthostatic hypotension  182–­183, 207 OST see opioid substitution treatment osteoporosis, anorexia nervosa risk  794 overdose, psychotropics in  913–­920 oxazepam catatonia treatment  155 concentration in normal dosing and UK legal limit  923 use in patients with hepatic impairment  761 oxcarbazepine, risks in pregnancy  724 P450 (CYP) pathways inhibition by different SSRIs  339 see also cytochrome function packed cell volume, psychotropic agent effects  966 paediatric autoimmune neuropsychiatric disorder associated with Streptococcus (PANDAS)  617 pain control for patients on opioid substitution treatment  518–­519 see also analgesics paliperidone pharmacokinetics  81 target range  869 use in patients with hepatic impairment  761 paliperidone palmitate long-­acting injections  29, 31, 93–­98 dose and administration  11, 77, 93 pancreatitis  246 panic disorder NICE guidelines  448 specific drugs used  450–­451 SSRIs/SNRIs  446–­447 use of benzodiazepines  446 paracetamol (acetaminophen) for behavioural and psychological symptoms of dementia  668 hepatotoxicity  762 pain in alcohol withdrawal  489 safety in older patients/dementia  660 paradoxical disinhibitory/aggressive drug reactions, benzodiazepines  471–­473 parenteral thiamine, prophylaxis against Wernike’s encephalopathy in alcohol dependency  484–­485 994 Index parenteral treatment, for acutely disturbed/ violent patients  62–­65 parkinsonian symptoms dementia with Lewy bodies  648 see also pseudoparkinsonism Parkinson’s disease (PD)  840–­844 cholinesterase inhibitors  842 complementary therapies  842 depression  840 and nicotine  910 pimavanserin use  842 psychiatric adverse effects of treatments  970 psychosis  841–­842 parotid gland swelling  246 paroxetine in pregnancy  720 use in patients with hepatic impairment  761 paroxysmal atrial fibrillation  845 pathological laughing or crying (pseudobulbar affect), multiple sclerosis  836 patient factors, affecting adherence  940–­942 patient monitoring bipolar disorder  283, 291, 297, 308–­309 mitigating serious consequences of non-­adherence  928 plasma level monitoring of psychotropic drugs  865–­878 PD see Parkinson’s disease PDSS see post-­injection delirium sedation syndrome penfluridol  43, 106–­107 people with epilepsy (PWE)  811–­819 driving restrictions  817 drug interactions between antiseizure medications and psychotropics  813–­814 possible causes of psychiatric symptoms  811–­812 prescribing principles  811 psychiatric comorbidities  811–­812 psychiatric side effects of antiseizure medications  812–­813 seizure risk from psychotropic drugs  814–­817 people living with human immunodeficiency virus (PLWH)  803–­810 bipolar affective disorder  805 depression  804–­805 factors contributing to psychiatric symptoms  803 prescribing principles  803–­804 psychosis  804 secondary mania  805 see also human immunodeficiency virus pericardial effusion  246 pericarditis  246 pericyazine  11, 14 perimenopause  857, 861 perioperative blood loss, SSRI risks  436–­437 permanent atrial fibrillation  845 perospirone  12 perphenazine  11, 14, 43 Perseris (RBP-­7000)  101–­102 persistent atrial fibrillation  845 personal and cultural beliefs, influencing adherence  940 personality disorders antipsychotic prescriptions  119, 331 benzodiazepines causing disinhibition  472 substance misuse  477 see also borderline personality disorder P-­glycoprotein (P-­gp)  883 pharmacodynamic drug interactions with alcohol  897–­898 antidepressants  339, 402, 404–­405 antiretroviral drugs and psychotropics  807–­808 antiseizure medications and psychotropics  814 pharmacodynamics changes in older people  627–­628 menopause effects  858 pharmacokinetic drug interactions antidepressants  401–­402, 403 antiretroviral drugs and psychotropics  807 antiseizure medications and psychotropics  813 pharmacokinetics  865–­899 caffeine  902–­903 changes in older people  627, 628 cytochrome function  883–­891 depot antipsychotics  81 drug interactions with alcohol  895–­899 half-­life increased in hepatic impairment  754 impaired drug absorption following bariatric surgery  849 menopause effects  858 plasma level monitoring of psychotropic drugs  865–­878 postmortem blood concentrations  879–­880 smoking and psychotropic drugs  892–­894 phenothiazines, in overdose  916 phenytoin, target range  869 phosphate in blood, psychotropic agent effects  964 pimavanserin  8, 12, 15, 208 managing behavioural and psychological symptoms of dementia  675 use in Parkinson’s disease  842 pitolisant  761, 778, 917 placebo and nocebo effects, patient expectations of treatment  941 plasma creatine kinase (CK)  150 plasma drug levels, elevated due to reduced hepatic blood flow  753 plasma glucose levels, antipsychotic medication monitoring  40 plasma level monitoring of psychotropic drugs  865–­878 amisulpride  869–­870 aripiprazole  870 clozapine  870–­871, 881–­882 first-­order pharmacokinetics  865 interpretation of results  867 olanzapine  871–­872 quetiapine  872–­873 risperidone  873 sampling time  866, 868–­869 steady state  865–­866, 868–­869 target ranges  867–­869 plasma levels risperidone long-­acting injections  99 variations in  56–­57 plasma lipids  169–­173 screening and monitoring  170, 171 see also dyslipidaemia plasma protein synthesis reduction, hepatic impairment  753 platelets agents associated with aggregation  967 psychotropic agent effects  967 SSRI effects bleeding  393–­394, 404, 409, 432–­437 decreasing embolic events/MI risk  433 plecanatide, for constipation treatment  265 PMDD see premenstrual dysphoric disorder PMR see postmortem redistribution PMS see premenstrual syndrome pneumonia, antipsychotic-­induced  204–­206, 242 polypharmacy, menopausal women  858 polyserositis  246 polysubstance abuse benzodiazepine dependence  541, 542 opioids and cocaine, substitution therapy reducing both  534 polyunsaturated fatty acids (PUFAs) see omega-­3 fatty acids PORT see Program of Rehabilitation and Therapy study positive predictive value (PPV)  275 post-­injection delirium sedation syndrome (PDSS)  76, 77, 91 post menopause, continuous combined HRT  861 postmortem blood concentrations  879–­880 postmortem redistribution (PMR)  879 postpartum depression  719 postpartum haemorrhage, antidepressant use in pregnancy  435–­436, 720, 721, 722 postpartum medication, breastfeeding mothers  734–­737 postpartum psychosis  715 post-­SSRI sexual dysfunction (PSSD)  428–­429 post stroke depression  393–­396 prophylaxis  393 SSRI risks  393–­394 post-­traumatic stress disorder (PTSD) benzodiazepine use  446 children and adolescents  595–­596 specific drugs used  452 SSRIs/SNRIs  447 postural hypotension see orthostatic hypotension potassium levels, psychotropic agent effects  964 power to treat, under S58 of the Mental Health Act  949–­950 PPH see postpartum haemorrhage PPIs see proton pump inhibitors PPV see positive predictive value pramipexole, bipolar depression  321 pregabalin generalised anxiety disorder  447–­448 in overdose  917 in pregnancy  724–­725 use in opiate misusers  519 use in patients with hepatic impairment  761 pregnancy  713–­733 alcohol use  492–­493 benzodiazepines  541 depression/antidepressants  719–­726 evidence of psychotropic drug effects  713 gynaecological and obstetric haemorrhage risk  435–­436 newly diagnosed mental illness  714 planning when taking psychotropic drugs  714 psychiatric illness as risk factor  713 psychosis  715–­718 selective serotonin reuptake inhibitors  435–­436, 720–­721 substance misuse  492–­493, 554–­559 tricyclic antidepressants  719–­720 in women taking psychotropic drugs  714 premature ejaculation, antidepressants as treatment  426, 428 premenstrual dysphoric disorder (PMDD)  474 medical menopause using gonadotrophin-­ prescribers, duty of, medical conditions and safe driving  924 prescribing checklists, relational aspects  942–­943 prescribing drugs outside their licensed indications (off-­label)  945–­948 legal issues  945–­946 recommendations  946–­948 preterm delivery risk antidepressants  720 antipsychotics  716, 717 lithium  723 tricyclic antidepressants  720 primavanserin  43, 916 procedural memory, clinicians’ unconscious influences  939 prochlorperazine  117, 118 pro-­drugs, not recommended in hepatic impairment  754 Product Licences  945 Program of Rehabilitation and Therapy (PORT) study  112 prolactin levels antidepressant effects  420–­422 antipsychotic medication monitoring  41 elevation  43, 44 menopausal women  860 psychotropic agent effects  190, 964 prolonged QT interval see QTc prolongation prolonged-­release injection, buprenorphine/ Buvidal  509–­510 prolonged release preparations, see also extended release preparations; long-­acting injectable antipsychotics; modified-­release preparations; slow-­release oral morphine promazine  43 promethazine acutely disturbed or violent behaviour in schizophrenia  63, 64, 68 breastfeeding  746 not recommended for managing behavioural and psychological symptoms of dementia  674 in pregnancy  726 prophylaxis antidepressants  397–­400 after first episode of depression  397 dosing  399 post stroke  393 for recurrent depression  397–­398 bipolar disorder  281, 290, 326–­330 lithium for depression/mood disorders  281 post stroke depression  393 thiamine for Wernicke’s encephalopathy in alcohol dependency  487–­488 propranolol, for tardive dyskinesia  137 protein in blood, psychotropic agent effects  964 proteinuria, renal impairment assessment  766 releasing hormone agonists  475 premenstrual syndrome (PMS)  474–­475 hormonal treatment  474–­475 medical menopause using gonadotrophin-­ releasing hormone agonists  475 non-­hormonal treatment  474 pharmacological management chart  474 prenatal exposure to medications see pregnancy pre-­school children, anxiety disorders  586 Index prothrombin time (PT), psychotropic agent effects  967 proton pump inhibitors (PPIs), safety in older patients/dementia  662 prucalopride, for constipation treatment  265 pseudobulbar affect, multiple sclerosis  836 pseudoparkinsonism (drug-­induced parkinsonism)  34, 35, 43, 44, 50, 126, 127, 128, 291, 804 PSSD see post-­SSRI sexual dysfunction psychiatric adverse effects of non-­ psychotropic drugs  969–­974 antiretroviral therapy  808–­809 differential diagnosis  972–­973 drugs and effects  969–­972 Naranjo scale  972, 973 psychiatric symptoms in the context of other disorders  803–­864 psychodynamic interventions adherence  929 depression  336 psychoeducation  932 psychological/psychosocial interventions anorexia nervosa  795 anxiety spectrum disorders  448 behavioural disturbance in people with learning difficulties  825 benzodiazepine withdrawal  466, 468, 541, 542 borderline personality disorder  787 children and adolescents  566, 568, 587, 597 depression  336, 337, 566, 568 improving medication adherence  932, 933–­934 learning disabilities  825 schizophrenia  29, 52, 53, 54, 230 see also cognitive behavioural therapy; dialectical behaviour therapy psychosis acute behavioural disturbance  62–­73 atrial fibrillation patients  846 cannabis  36 catatonic stupor in  155 children and adolescents  580–­581 during pregnancy  715–­718 electroconvulsive therapy  108–­110 first episode  28–­29, 31 duration of treatment  54 negative symptoms  34 NICE guidelines  52–­53 treatment algorithm  45 gamma-­butyrolactone withdrawal  534, 537 Huntington’s disease  832, 833 menopausal women  858–­860 methamphetamine use disorder  534–­535 multi-­episode  29–­30 multiple sclerosis  836–­837 and nicotine  908–­909 996 Index psychosis (cont’d) oestrogen augmentation in menopausal women  860 oestrogen decline reducing antipsychotic activity in menopausal women  858 people living with human immunodeficiency virus  804 postpartum  715, 736 prevention with polyunsaturated fatty acids  111–­114 relapse, withdrawal-­associated  119 and sexual dysfunction  195–­196 ‘super-­sensitivity psychosis’  31 use of benzodiazepines  461 see also schizophrenia and related psychoses psychosocial interventions see psychological/ psychosocial interventions psychostimulants attention deficit hyperactivity disorder in adults  798, 799, 800 depression  388–­392 psychotherapies, post-­traumatic stress disorder  595 psychotic depression  362–­365 acute treatment  362 combination therapies  362, 364 ECT treatment  363 ketamine  363 maintenance treatment  363–­364 psychotropic drugs with alcohol  895–­899 driving impairment  921–­926 interactions with illicit drugs  545, 546–­548 in overdose  913–­920 plasma level monitoring  865–­878 steady state  865–­866, 868–­869 target ranges  867–­869 smokers  892–­894 target ranges  867–­869 use in renal impairment  769–­778, 779 PT see prothrombin time PTSD see post-­traumatic stress disorder PUFAs see polyunsaturated fatty acids PUFAs (polyunsaturated fatty acids) see omega-­3 fatty acids pure red cell aplasia, psychotropic agent effects  967 PWE see people with epilepsy pyridoxine, for tardive dyskinesia  136 QTc prolongation antipsychotic-­related  43, 44, 161–­168 cardiovascular risk factors  166 ECG monitoring  165 management  166 metabolic inhibition  165 non-­psychotropic association  165 physiological risk factors  164 QT interval  161–­162 risk factors  164–­165 risk quantification  162–­164 switching antipsychotics  207 methadone risk  506 prescribing in atrial fibrillation patients  845 quercetin Alzheimer’s disease management  645 for tardive dyskinesia  137 questionnaires adherence assessment  930, 931 severity of alcohol dependence  480, 482, 485 quetiapine acute kidney injury risk  769 bipolar disorder  302 borderline personality disorder  788 glucose tolerance impairment association  175 in overdose  916 plasma level monitoring  872–­873 rapid-­cycling bipolar affective disorder  316 risks in pregnancy  717 target range  869 thyroid function tests  41 weight restoration in anorexia nervosa  792 patient factors  940–­942 prescribing checklist  942–­943 relational aspects of prescribing practice  939–­944 relative infant dose (RID), medication in breastfeeding mothers  734 renal adverse effects antiretrovirals  807 lithium  282 renal function, NSAIDs affecting sodium/ lithium reabsorption  285 renal impairment in patients  766–­785 anti-­dementia drugs  778 antidepressants  772–­775 antipsychotics  769–­771 anxiolytics and hypnotics  776–­777 classification of stages  767 clinical guidance  768 lithium  282 methadone  505 monitoring  768 mood-­stabilisers  775–­776 other psychotropic drugs  768 recommended psychotropic drugs  779 repetitive transcranial magnetic stimulation (rTMS) for catatonia  155–­156 for negative symptoms in schizophrenia  36 for tardive dyskinesia  137 restarting psychotropic medications after a break in treatment  234–­235 after neuroleptic malignant syndrome  150 after period of non-­compliance  937–­938 restlessness (akathisia)  43, 44, 127, 128, 131–­134 restraint, exacerbating risks in drug-­induced excited states  543 restricted repetitive behaviours and interests (RRBIs), core symptom of autism spectrum disorder  606 reticulocyte count, psychotropic agent effects  967 re-­titration, after period of non-­adherence to medication regime  937, 938 RID see relative infant dose rilpivirine, psychiatric adverse reactions  809 risk awareness, clinician responsibilities to patients  945 Risperdal Consta  99–­101, 103 risperidone  2, 3, 8, 29, 58, 228 bipolar disorder  302, 305–­306 clozapine augmentation  221 efficacy  3, 17 equivalent dose  15 glucose tolerance impairment association  175 maximum dose  11 maximum doses  12 in overdose  916 raloxifene  228, 860 see also selective oestrogen receptor modulators rapid-­cycling bipolar affective disorder  290, 316–­318 rapid tranquilisation (RT)  62, 68–­70 children and adolescents  623–­625 physical monitoring  69 remedial measures  70 site of administration of intramuscular injections  956–­957 Rating of Medication Influences (ROMI) scale  931 RBP-­7000 (Perseris)  101–­102 readiness to change, influencing adherence  940 recommendations to patients, adherence  927 rectal administration, antipsychotics  116, 118 recurrent depression, prophylaxis  397–­398 red blood count/red cell distribution width, psychotropic agent effects  967 reduced hepatic blood flow, consequences of hepatic impairment  753 reduced metabolism of drugs changes with old age  628 hepatic impairment  753 refractory schizophrenia see treatment-­resistant schizophrenia refusal of treatment, older people’s mental health and capacity  629, 694–­699 relational aspects of adherence clinician factors  939 pharmacokinetics  81 plasma level monitoring  873 possible teratogen  716 relative adverse effects  43 target range  869 use in children and adolescents with autism spectrum disorder  609, 610 weight restoration in anorexia nervosa  792 risperidone intramuscular injection (Rykindo)  100, 103 risperidone ISM (in situ microparticles)  81, 100, 101, 103, 873, 956 risperidone long-­acting injections (RLAIs)  12, 15, 81, 99–­105, 103 approximate dose equivalence  94 bipolar disorder  305–­306 blood levels following discontinuation  99 doses and frequencies  78 equivalent doses  103 intramuscular injections  99–­101 plasma concentrations timescale  99 Rykindo  100, 103 subcutaneous injections  101–­102 switching from  100 RISQ-­PATH study  163 Risvan see risperidone ISM rivastigmine, Alzheimer’s disease  630–­636, 639, 642 RLAIs see risperidone long-­acting injections road traffic accidents (RTAs), psychotropic drugs and driving impairment  922 ROMI see Rating of Medication Influences scale routine monitoring, mitigating serious consequences of non-­adherence  928 Roux-­en-­Y gastric bypass (RYGB)  849 RRBI see restricted repetitive behaviours and interests RT see rapid tranquilisation RTAs see road traffic accidents rTMS see repetitive transcranial magnetic stimulation RYGB see Roux-­en-­Y gastric bypass Rykindo see risperidone intramuscular injection antipsychotic response  55–­61 atrial fibrillation patients  846 caffeine effects  904 cardiometabolic risk factors  169 catatonia  155 comorbid alcohol use disorder  495–­496 diabetes association  174 electroconvulsive therapy  108–­109 first episode  28–­29, 31 duration of treatment  54 negative symptoms  34 treatment algorithm  45 maintenance treatment  29, 53 multi-­episode  29–­30 negative symptoms  34–­39 NICE guidelines  2, 53–­54 and nicotine  908–­909 people with 22q11.2 deletion syndrome  822 people living with human immunodeficiency virus  804 poorly responsive to standard antipsychotic treatment  57–­59 prescribing practice for  17 QTc prolongation  161 relapse  28, 29, 30, 31 withdrawal-­associated  120 relapse/acute exacerbation, treatment algorithms  46–­47 suicide risk  29 ‘super-­sensitivity psychosis’  31 treatment adherence  30, 928–­929, 933–­934 algorithms  45–­48 NICE guidelines  2, 52–­54 polyunsaturated fatty acids  111–­114 for poorly responsive schizophrenia  57–­59 treatment-­resistant  18, 53–­54, 108–­109, 214–­233 see also antipsychotics second-­generation antidepressants anorexia nervosa  794 see also bupropion; monoamine oxidase inhibitors; tricyclic antidepressants second-­generation antipsychotics (SGAs)  49, 50 adverse effects  3–­4 bipolar disorder  300–­302 borderline personality disorder  788 children and adolescents  568, 573, 580, 590, 608, 615, 623 classification  2 diabetes, antipsychotic-­related  174–­176 equivalent doses  14, 15 long-­acting injectable antipsychotics  4, 75 maximum doses  11, 12 minimum effective doses  8 neuroleptic malignant syndrome association  151 ‘off-­label’ prescribing  947 SADQ see Severity of Alcohol Dependence Questionnaire safer prescribing, older people/ dementia  654–­666 saffron see Crocus sativus St John’s wort (SJW) (Hypericum perforatum), treating depression  440–­443 SAWS see Short Alcohol Withdrawal Scale schizoaffective disorder, atrial fibrillation patients  846 schizophrenia and related psychoses  1–­277 acute behavioural disturbance  62–­73 adherence to treatment  30 Index optimal dosage  55 people with learning difficulties  826 people living with human immunodeficiency virus  804 in pregnancy  716–­717 relative efficacy  3 site of administration of intramuscular injections  955–­956 treatment algorithm  46 treatment of negative symptoms  35 Second Opinion Appointed Doctor (SOAD), the Mental Health Act  950–­951, 953 sedation  43, 44 alcohol effects  897 management  242 medication-­induced  923 over-­sedation  64 switching antipsychotics  207 sedatives antihistamines not recommended for behavioural and psychological symptoms of dementia  674 ‘high-­dose sedation’  64 in pregnancy  726–­727 respiratory depression role in death from opioid agonists overdose  545 use in patients with hepatic impairment  754, 760, 761 see also benzodiazepines; promethazine seizures antiretrovirals  808 drug risks for people with 22q11.2 deletion syndrome  820, 821–­822 management  242, 882 psychotropic drug risks in people with epilepsy  814–­817 severe alcohol withdrawal  480, 481 selective oestrogen receptor modulators (SERMs) psychosis treatment adjunct for menopausal women  860 see also raloxifene selective serotonin reuptake inhibitors (SSRIs) adverse effects relative to other antidepressants  338 anxiety spectrum disorders  446–­447 arrhythmia risk  411 atrial fibrillation patients  845, 846 bipolar depression  322 bleeding risks  432–­439 gastrointestinal  433–­434 gynaecological and obstetric haemorrhage  435–­436 intracranial/intracerebral haemorrhage  434–­435 mechanisms  432 post stroke depression  393–­394 risk factors  432–­433 surgical and postoperative  436–­437 998 Index selective serotonin reuptake inhibitors (SSRIs) (cont’d) body dysmorphic disorder  447 with caffeine  903 cardiac effects  406–­408, 409, 411–­412 co-­prescribed with low-­dose aspirin/ NSAIDs, GI bleeding risk  433, 434 co-­prescribed with warfarin, non-­GI bleeding risk  433, 434 driving impairment  922 gastric acid secretion effects  432 gastrointestinal effects  432, 433–­434 generalised anxiety disorder  446 hyperprolactinaemia induction  420 hyponatraemia induction  416, 417, 418 increased free plasma levels in hepatic impairment  753–­754 increased risk of bleeding in hepatic impairment  753 interactions with anticoagulants  846 lithium interactions  286 obsessive compulsive disorder  447 in overdose  914 panic disorder  446–­447 people with learning difficulties  826 people living with human immunodeficiency virus  805, 806 pharmacodynamic drug interactions  404 pharmacokinetic drug interactions  401 platelet effects  393–­394, 404, 409, 432, 433 bleeding  432–­439 decreasing embolic events/MI risk  433 post stroke depression  393–­394 post-­traumatic stress disorder  447 in pregnancy  720–­721 premenstrual syndrome treatment  474 sexual dysfunction  199, 427, 428–­429 social phobia  447 type II diabetes improvement  423 use in children and adolescents  566–­567, 583–­584, 585, 588 withdrawal symptoms  373 semaglutide, for antipsychotic-­induced weight gain  146 SERMs see selective oestrogen receptor modulators serotonergic antidepressants, treatment of sexual dysfunction  426, 428 serotonin-­noradrenaline reuptake inhibitors (SNRIs) anxiety spectrum disorders  446–­447 hyperprolactinaemia induction  420 hyponatraemia induction  416, 417 pharmacokinetic drug interactions  401, 404 in pregnancy  720 use in children and adolescents  583, 584, 585, 592, 598 serotonin reuptake inhibition see selective serotonin reuptake inhibitors serotonin syndrome renal impairment  769 switching antidepressants  367 sertindole  11, 15, 43, 228 sertraline bulimia nervosa/binge eating disorder  794 ‘off-­label’ prescribing  947 in pregnancy  720 use in patients with hepatic impairment  761 severe alcohol dependence  480, 486 severe alcohol withdrawal  481, 484 Severity of Alcohol Dependence Questionnaire (SADQ)  480, 482, 485 sexual behaviour (inappropriate) in older people  680–­687 sexual drive reduction by hormone implants  682 sexual dysfunction antidepressants  426–­431 effects of antipsychotics  195–­203, 196–­197, 207 effects of psychosis  195–­196 management of antidepressant effects  428–­429 selective serotonin reuptake inhibitors  199, 427, 428–­429 treatment  198, 199 SGAs see second-­generation antipsychotics Short Alcohol Withdrawal Scale (SAWS)  482, 484, 485, 486 SIADH see syndrome of inappropriate antidiuretic hormone sialorrhoea see hypersalivation site of administration of intramuscular injections  954–­958 SJW see St John’s wort skin diseases, and antipsychotics  246 sleep disturbance children and adolescents autism spectrum disorder  609–­610 use of melatonin  575, 609–­610, 620–­622 managing behavioural and psychological symptoms of dementia  674 see also insomnia slow-­release oral morphine (SROM)  514 smokers/non-­smokers, clozapine dosing regimens  216–­218 smoking with caffeine  903 cessation  523–­531, 909 pregnant women with mental illness  714 and psychotropic drugs  892–­894 see also nicotine SNRIs see serotonin-­noradrenaline reuptake inhibitors SOAD see Second Opinion Appointed Doctor social and communication impairment, core symptom of autism spectrum disorder in children and adolescents  606 social phobia (social anxiety disorder)  447, 454–­455 sodium levels lithium toxicity  283, 284–­286 psychotropic agent effects  964 sodium oxybate, for tardive dyskinesia  137 sodium valproate clozapine augmentation  221 ‘off-­label’ prescribing  947 solriamfetol in overdose  917 use in patients with hepatic impairment  761 use in renal impairment  778 Souvenaid (dietary supplement), Alzheimer’s disease management  644 special educational needs see learning difficulties SROM see slow-­release oral morphine SSRIs see selective serotonin reuptake inhibitors statins no evidence for benefit in vascular dementia  647 preventing cardiovascular events  170, 171 safety/use in older patients  661 vascular dementia  647 stimulants attention deficit hyperactivity disorder in adults  798, 799, 800 breastfeeding mothers  747 definition  532 depression  388–­392 use in patients with hepatic impairment  760 see also psychostimulants stimulant use disorder (SUD)  532–­536 amfetamines/ methamphetamine  533–­534 cocaine  533 depression/anhedonia from abstinence  535 polysubstance abuse, opioids plus cocaine  534 psychotic symptoms  534–­535 stopping medication abrupt cessation by non-­compliant patients  928 antidepressants  339, 378 antipsychotics  119–­125 benzodiazepines  466 lithium  331–­334 long-­acting antipsychotics reducing impacts of non-­adherence  932–­933 see also withdrawal sulpiride  8, 11, 14, 43 clozapine augmentation  221 clozapine-­induced hypersalivation treatment  260 typical or atypical classification  2 use in patients with hepatic impairment  754, 756, 761 see also amisulpride suppositories, antipsychotics  116, 118 surgical and postoperative bleeding, SSRI risks  436–­437 surgical procedures, bariatric surgery  849–­856 suvorexant managing sleep disturbance in dementia  674 in overdose  917 use in patients with hepatic impairment  761 switching between drugs antidepressants  366–­372 general guidelines  366–­367 swapping and stopping guide  368–­370 timing  345–­346 within and between drug classes  345 symptom-­triggered regimen, benzodiazepines for alcohol withdrawal management  485 syndrome of inappropriate antidiuretic hormone (SIADH)  186, 188 synthetic cannabinoids  543 stroke antipsychotic risks  212–­213, 669 dyslipidaemia  171 post stroke depression  393–­396 stupor see catatonia stuttering, and antipsychotics  246 sublingual administration antipsychotics  115, 117 buprenorphine  503, 507–­508 Suboxone (buprenorphine with naloxone)  513 substance misuse and dependence alcohol  479–­497 benzodiazepine misuse  540–­542 concurrent alcohol and other substance use disorders  493–­494 drugs of misuse summary  549–­553 dual diagnosis with mental illness  477 illicit drug interactions with prescribed psychotropic drugs  545–­548 mixed substance use  532 mutual aid and peer support for stimulant abstinence  532 nicotine dependence  523–­531 opioid dependence  498–­522 people living with human immunodeficiency virus  806 personality disorders  477 pregnancy  554–­559 stimulant use disorder  532–­536 SUD see stimulant use disorder sudden cardiac death, antidepressants  411, 412 suicidality antidepressant cessation  339 antidepressant use in adolescents and young adults  339 antidepressant use balance  339 body dysmorphic disorder in children and adolescents  587, 588 cognitive behavioural therapy decreasing effects of fluoxetine  566 depression in children and adolescents  570–­571 environmental lithium effects  279 fluoxetine use in children and adolescents  566, 570–­571, 588, 610 Huntington’s disease  832, 833 lithium reducing risk in bipolar and unipolar depression  281, 284 non-­adherence impacts  928 obsessive compulsive disorder in children and adolescents  587, 588 overdose of psychotropics  913 peri-­natal risks from psychotropic medication withdrawal  713 psychotic depression  362 PTSD in children and adolescents  595 schizophrenia  29 SSRI use in children and adolescents  566, 570–­571, 584, 588, 610 valproate risk  291 tachycardia, clozapine effects  184, 234, 242, 253, 255 tapering antidepressants  366, 376, 378–­382 benzodiazepines  466–­469 drug formulation problems  382 z-­drugs/gabapentinoids  469 tardive dyskinesia (TD)  3, 29, 50, 120, 127, 128 switching antipsychotics  208 treatment  135–­140 tDCS see transcranial direct current stimulation temazepam concentration in normal dosing and UK legal limit  923 use in patients with hepatic impairment  761 use in patients with renal impairment  777 teratogenic potential antidepressants  721, 722 carbamazepine  297, 714, 723–­724 first generation antipsychotics  715–­716 mood stabilisers (eg valproate)  714, 723–­724 second generation antipsychotics  716–­717 valproate  292 Index test doses, long-­acting injectable antipsychotics  75 testosterone in blood, psychotropic agent effects  964 tetrabenazine Huntington’s chorea  831 tardive dyskinesia  136 theophylline, safety in older patients/ dementia  659 therapeutic threshold  867 thiamine deficiency (Wernicke’s encephalopathy), alcohol dependency  487–­488 thiamine (vitamin B1) injections, alcohol withdrawal adjunctive treatment  484–­485 thiazide diuretics, lithium interaction  285 thrombocytopenia  246, 291, 745, 820 thromboembolism  211–­213, 246, 253, 860 thyroid adverse effects, lithium  282 thyroid function tests, antipsychotic medication monitoring  41 thyroid-­stimulating hormone, psychotropic agent effects  964 thyroxine in blood, psychotropic agent effects  964 tics and Tourette’s syndrome children and adolescents  614–­619 adrenergic a2 agonists  615 antipsychotics  615–­616 comorbid conditions  614 education and behavioural treatments  614 pharmacological treatments  614–­615 recommended treatments  617 TMS see transcranial magnetic stimulation tobacco see nicotine; smoking tolerance, dependence syndrome  477–­478 topical vaginal oestrogen  862 topiramate  35, 228 for antipsychotic-­induced weight gain  146 borderline personality disorder  789 clozapine augmentation  221 teratogenic risk  714, 724 torsades de pointes, methadone risk  506 Tourette’s syndrome (TS) children and adolescents  614–­619 see also tics training of practitioners, compliance therapy and adherence  933–­934 tranquilisation see rapid tranquilisation transaminases, drug induced increase in hepatic impairment  754 transcranial direct current stimulation (tDCS)  36, 156 transcranial magnetic stimulation (TMS) stimulant use disorder  533 see also repetitive transcranial magnetic stimulation 1000 Index transdermal patches antipsychotics  116 equivalent doses  15 maximum doses  12 nicotine  494, 524, 616 trazodone Alzheimer’s disease management  645 driving impairment  922 increased free plasma levels in hepatic impairment  753–­754 in overdose  915 in pregnancy  721 smokers  893 TRBD see treatment-­resistant bipolar disorder TRD see treatment resistant depression treatment framework, clinicians using knowledge of their normal practices to avoid psychological factors influencing decision-­making  939 treatment preferences of patients, affecting outcomes  941–­942 treatment-­resistant bipolar disorder (TRBD), clozapine  301–­302 treatment resistant depression (TRD)  348–­356 addition of extra drugs  348–­349, 351 commonly used treatments  348–­350 ketamine  351, 357–­361 less commonly used treatments  351–­352 potential therapies  353–­356 treatment-­resistant schizophrenia (TRS)  18 and clozapine  214–­233 alternatives to clozapine  226–­233 dosing regime  214–­218 intramuscular clozapine  219 treatment optimisation  220–­225 NICE guidelines  53–­54 tremor see pseudoparkinsonism tricyclic antidepressants (TCAs) adverse effects relative to other antidepressants  338 with alcohol  899 arrhythmogenic activity  411 driving impairment  922 hyperprolactinaemia  420, 420 increased free plasma levels in hepatic impairment  753–­754 not recommended for managing behavioural and psychological symptoms of dementia  673 in overdose  915 people living with human immunodeficiency virus  805 pharmacodynamic drug interactions  404 pharmacokinetic drug interactions  402 in pregnancy  719–­720 psychotic depression  362 smokers  893 target range  869 trifluoperazine  8, 11, 14, 44 triglycerides in blood, psychotropic agent effects  965 triiodothyronine in blood, psychotropic agent effects  965 TRS see treatment-­resistant schizophrenia TS see Tourette’s syndrome TV-­46000 see Uzedy typical/atypical antipsychotic classification  1–­2 tyramine-­containing foods, monoamine oxidase inhibitor interactions  338–­339 adverse effects  526 clinical effectiveness  525 nicotine addiction  524–­526 preparations and doses  526, 529 vascular dementia (VaD)  647 velocardiofacial syndrome (22q11.2 deletion syndrome)  820–­823 venlafaxine in overdose  915 possible teratogen  721 venous thromboembolism (VTE) antipsychotic risks  211–­213 clozapine adverse effects  253 oestrogen augmentation risk in menopausal women  860 risk of pathological blood clotting  212 Vienna High Risk (VHR) study  111 viloxazine, attention deficit hyperactivity disorder in adults  799, 801 violent behaviour see acutely disturbed/ violent behaviour vitamin B1 (thiamine), alcohol withdrawal adjunctive treatment  484–­485 vitamin B6 akathisia adjunctive treatment  131 hyperprolactinaemia  191 vitamin D3 intake, hyperprolactinaemia  191 vitamin D supplementation anorexia nervosa  793 fatigue in multiple sclerosis  837 vitamin E for tardive dyskinesia  136 vitamin K, prophylactic if caprbamazepine given in pregnancy  724, 726 vitamin K-­dependent clotting factor synthesis reduction, hepatic impairment  753 vitamin and mineral supplements, anorexia nervosa  793 vitamin replacement, alcohol withdrawal adjunctive treatment  484–­485 vitamin supplements Alzheimer’s disease management  643 hyperprolactinaemia  191, 192 VMAT2 inhibitors, Huntington’s chorea  831 vortioxetine in overdose  915 use in patients with hepatic impairment  761 VTE see venous thromboembolism UGIB see upper gastro-­intestinal bleeding UGT see uridine diphosphate glucuronosyltransferase unintentional non-­adherence  932 upper gastro-­intestinal bleeding (UGIB), antidepressants  433 urate (uric acid) in blood, psychotropic agent effects  965 urea in blood, psychotropic agent effects  40, 965 urgent treatment, S62 of the Mental Health Act  952, 953 uridine diphosphate glucuronosyltransferase (UGT)  883 urinary incontinence, anticholinergic drugs  658 urine testing for illicit drugs, in psychiatric care settings  549 Uzedy (TV-­46000) risperidone injections  12, 15, 81, 101–­102, 103 VaD see vascular dementia vaginal bleeding abnormalities, SSRI risks  435 valbenazine for tardive dyskinesia  136 use in patients with hepatic impairment  761 use in renal impairment  778 valproate  229, 883 adverse effects  291 bipolar disorder  289–­294, 310, 311 borderline personality disorder  789 discontinuation  291, 292 drug interactions  292 formulations  289, 292 indications  289–­290, 292 mechanism of action  289 not recommended for dementia patients  673 in overdose  916 pharmacokinetics  290 plasma levels  290 prescribing  292 pre-­treatment tests and monitoring  291, 292 restricted use  311 target range  869 teratogenic risk  292, 714, 723–­726 use in pregnancy  714, 723–­726 vaping see nicotine vaping devices varenicline warfarin atrial fibrillation patients  845, 846 co-­prescribed with SSRIs, non-­GI bleeding risk  433, 434 water intoxication  186 WCC see white cell count weight changes after bariatric surgery  854 antipsychotic medication monitoring  40 weight gain  43, 44, 141–­149 after bariatric surgery  854 dose-­response  142 drugs to aid weight restoration in anorexia nervosa  792 management  242 risk/extent of  141–­142 switching antipsychotics  208 time course  142 treatment  144–­149 Wernicke-­Korsakoff syndrome  485 Wernicke’s encephalopathy (thiamine deficiency), alcohol dependence  487–­488 white cell count (WCC)  267, 268, 269, 271 withdrawal antipsychotics  119–­120, 123 benzodiazepines  464–­465, 540–­542 buprenorphine  501, 516–­517 caffeine  902 gabapentinoids  464, 469 gamma-­hydroxybutyrate or gamma-­ butyrolactone  534, 537–­539 lithium and other mood stabilisers, bipolar disorder  331 methadone  516 non-­adherence impacts  937 role of hyperbolic tapering  379 z-­drugs  464, 469 see also alcohol withdrawal; antidepressant withdrawal; opioid withdrawal women of child-­bearing potential avoid contra-­indicated drugs even if not planning pregnancy  714 see also teratogenic potential xanomeline  8, 12, 15, 44 xanomeline-­trospium (KarXT), Alzheimer’s disease management  645 Index ZA see zuclopenthixol acetate z-­drugs (zolpidem/zopiclone/zaleplon) breastfeeding  746 dependence and withdrawal  464, 469 insomnia in dementia patients  674 in overdose  917 in pregnancy  727 for tardive dyskinesia  137 use in patients with hepatic impairment  761 ziprasidone  8, 12, 15, 17, 44, 229 clozapine augmentation  221 in overdose  916 zonisamide, for antipsychotic-­induced weight gain  146 zotepine  229 zuclopenthixol  11, 14, 44, 893 zuclopenthixol acetate (ZA)  66–­67 zuclopenthixol decanoate  12, 14, 81