34 - A guide to medication doses of commonly used

A guide to medication doses of commonly used psychotropics in older adults, [1] / National Institute for Health and Care Excellence (NICE).

700 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 6 A guide to medication doses of commonly used psychotropics in older adults, [1] / National Institute for Health and Care Excellence (NICE). Drug Specific indication/ additional notes Starting dose Usual maintenance dose Maximum dose in elderly Antidepressants Agomelatine Depression   Monitor LFTs   Data suggest agomelatine is not effective in patients

75 years 25mg nocte 25–50mg daily 50mg nocte Bupropion2 Depression Immediate release tablets: 100mg bd2   Sustained release tablets (SR): 150mg once daily2   Extended-­release tablets (XL): 150mg once daily2 May increase to 100mg tds after 3 days2   May increase dose to 150mg SR twice daily after 3 days2   May increase dose to 300mg XL once daily after at least 4 days2 300mg/day*   Consider reduced dosage and/or dosage frequency in patients with a CrCl <90mL/min2 Bupropion and dextromethorphan3 Depression   Each tablet contains 45mg dextromethorphan hydrobromide (equivalent to 32.98mg dextromethorphan base) in an immediate-­release formulation and 105mg bupropion hydrochloride (equivalent to 91.14mg bupropion base) in an XL formulation.3 1 tablet mane3 1 tablet bd (at least 8 hours apart; dose can be increased to bd after 3 days)3   Reduced dosage of 1 tablet mane is recommended for patients with moderate kidney impairment (eGFR 30–59mL/ min/1.73m2), those known to be poor CYP2D6 metabolisers and when co-­administered with strong CYP2D6 inhibitors. Concomitant use with strong CYP2B6 inducers should be avoided. 1 tablet bd3 Citalopram Depression/anxiety disorder 10mg mane 10–20mg mane 20mg mane Clomipramine Depression/phobic and obsessional states 10mg nocte (dose increases should be cautious) 30–­75mg daily4 should be reached after about 10 days. 75mg daily4

Prescribing in older people CHAPTER 6 Drug Specific indication/ additional notes Starting dose Usual maintenance dose Maximum dose in elderly Desvenlafaxine5 Major depression   No formal recommendations are available for dosing in older adults.5 However, possible reduced renal clearance of desvenlafaxine should be considered when determining an appropriate dose. 50mg daily   Dosage in renal impairment: CrCl 50–80mL/ min: no dosage adjustment needed CrCl 30–50mL/ min: 50mg daily is recommended daily and max. dose CrCl <30mL/min or ESRD: 50mg every other day is recommended daily and max. dose 50mg daily Usual dose 50mg/ day   Max. dose 400mg daily5 however no additional benefit was demonstrated at doses >50mg/ day and adverse reactions and discontinuations were more frequent at higher doses. Duloxetine Depression/anxiety disorder 30mg daily* 60mg daily 120mg daily6 (caution as limited data in elderly for this dose) Escitalopram Depression/anxiety disorder 5mg mane 5–10mg mane 10mg mane Fluoxetine Depression/anxiety disorder   Caution as long half-­life and inhibitor of several CYP enzymes 20mg mane 20mg mane 40mg mane usually (but 60mg can be used) Lofepramine Depression 35mg nocte* 70mg nocte* 140mg nocte or in divided doses* (occasionally 210mg nocte required) Mirtazapine Depression 7.5mg nocte or usually 15mg nocte* 15–30mg nocte 45mg nocte Sertraline Depression/anxiety disorder 25–50mg mane (25mg can be increased to 50mg mane after 1 week) 50–100mg mane* 100mg (occasionally up to 150mg mane)* Trazodone Depression 100mg daily in divided doses or as a single night ­time dose7 100–200mg daily* 300mg daily7 (Continued )

702 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 6 Drug Specific indication/ additional notes Starting dose Usual maintenance dose Maximum dose in elderly Agitation in dementia   Avoid single doses

100mg 25mg bd* 25–100mg daily* 200mg daily* (in divided doses) Venlafaxine Depression/anxiety disorder   Monitor BP on initiation 37.5mg mane (increased to 75mg XL mane after 1 week)* 75–150mg (XL) mane* 150mg daily (occasionally 225mg daily is necessary)* Vortioxetine8 Major depressive disorder   Vortioxetine is extensively metabolised in the liver, primarily by CYP2D6 and to a minor extent by CYP3A4/5 and CYP2C9. Co-­administration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. 5mg daily 5–10mg daily 10mg daily   Caution advised in ≥65 years with doses >10mg daily for which data are limited8 Antipsychotics† Amisulpride Chronic schizophrenia 50mg daily* 100–200mg daily* 400mg daily9 (caution >200mg daily)* Late life psychosis 25–50mg daily* 50–100mg daily* (increase in 25mg steps) 200mg daily10 (caution >100mg daily)* Agitation/psychosis in dementia   Caution QTc prolongation 25mg nocte11 25–50mg daily11 50mg daily11 Aripiprazole Schizophrenia, mania (oral) 5mg mane* 5-­15mg daily* 20mg mane* Control of agitation (IM injection) 5.25mg* 5.25–9.75mg* 15mg daily* (combined oral + IM) Brexpiprazole12 Schizophrenia12   Metabolism is primarily mediated by CYP3A4 and CYP2D6. Co-­administration of certain drugs may need to be avoided or dosage adjustments may be necessary. 0.5mg once daily On day 5 may increase to 1mg once daily   On day 8 may further increase to 2mg daily   4mg daily   Max. 3mg/day if CrCl <60mL/min, including ESRD12

Prescribing in older people CHAPTER 6 Drug Specific indication/ additional notes Starting dose Usual maintenance dose Maximum dose in elderly Further titration may be made weekly in 1mg increments based on response and tolerability. Recommended range: 2–4mg once daily12 Depression (adjunctive treatment) 0.5 once daily12 Target dose 2mg once daily. Titrate dosage at weekly intervals based on response and tolerability.12 3mg/day12   Max. 2mg/day if CrCl <60mL/min, including ESRD12 Agitation in Alzheimer’s disease 0.5mg once daily12 On day 8 increase dose to 1mg once daily for an additional 7 days.   On day 15 increase to 2mg po once daily, the recommended target dose.   May increase to 3mg once daily after at least 14 more days based on clinical response and tolerability.12 3mg/day12   Max. 2mg/day if CrCl <60mL/min, including ESRD12 Cariprazine13 Schizophrenia   Cariprazine and its major active metabolites are highly protein bound and extensively metabolised by CYP3A4 and, to a lesser extent, by CYP2D6. Co-­administration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. 1.5mg once daily13 May increase to 3mg once daily on day 2   Make further dose adjustments in 1.5mg increments based on response and tolerability.13   Effective range: 1.5–6mg po once daily14 6mg/day14 (Continued )

704 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 6 Drug Specific indication/ additional notes Starting dose Usual maintenance dose Maximum dose in elderly Mania or mixed episodes of bipolar disorder 1.5mg once daily14 May increase to 3mg once daily on day 2   Adjust dose by 1.5–3mg/day based on clinical response and tolerability   Usual dose: 3–6mg/day14 6mg/day for acute mania14 Bipolar depression and adjunctive treatment of major depressive disorder 1.5mg once daily14 May increase dose to 3mg/day after 2 weeks based on clinical response and tolerability14 3mg/day14 BPSD Dose not yet established14 Clozapine Schizophrenia 6.25–12.5mg daily,15,16 increased by no more than 6.25–12.5mg once or twice a week15 50–100mg daily15,16 100mg daily15,16 Parkinson’s related psychosis 6.25mg daily17 25–37.5mg daily17 50mg daily17 IM injection The oral bioavailability of clozapine is about half that of the IM injection (e.g. 50mg daily of the IM injection is roughly equivalent to 100mg daily of the tablets/oral solution). After each injection has been given the patient must be observed every 15 minutes for the first 2 hours to check for excess sedation.   NB If IM lorazepam is required, leave at least 1 HOUR between administration of IM clozapine and IM lorazepam. Iloperidone No formal recommendations are available for dosing in older adults18 Lumateperone19 Schizophrenia 42mg daily (equivalent to 60mg lumateperone tosylate)   Dose titration not required 42mg daily 42mg daily Lurasidone Schizophrenia 37mg once daily (or 18.5mg daily when given with concomitant moderate CYP3A4 inhibitors, max. dose 74mg once daily)   18.5–111mg daily20 Limited data on higher doses used in older adults. No data are available in elderly people treated with 148mg. Caution should be exercised when treating patients ≥65 years of age with higher doses.20

Prescribing in older people CHAPTER 6 Drug Specific indication/ additional notes Starting dose Usual maintenance dose Maximum dose in elderly Dosing for elderly with normal renal function (CrCl ≥80mL/min) is the same as for adults with normal renal function. In diminished renal function, dose adjustments may be required according to their renal function status.20 Olanzapine Schizophrenia 2.5mg nocte* 5–10mg daily* 15mg nocte16 Agitation/psychosis in dementia 2.5mg nocte* 2.5–10mg daily* 10mg nocte* (optimal dose is 5mg daily)16 Olanzapine and samidorphan No formal recommendations are available for dosing in older adults.21 Pimavanserin22,23 Treatment of hallucinations and delusions associated with Parkinson’s disease psychosis 34mg daily (or 10mg daily if co-­administered with strong CYP3A4 inhibitors)   Dose titration not required 34mg daily (or 10mg daily if co-­ administered with strong CYP3A4 inhibitors) 34mg daily (or 10mg daily if co-­administered with strong CYP3A4 inhibitors)   Monitor patients for reduced efficacy if used concomitantly with strong CYP3A4 inducers. Quetiapine Schizophrenia 12.5–25mg daily16 75–125mg daily15 200–300mg daily16 Agitation/psychosis in dementia 12.5–25mg daily* 50–100mg daily* 100–300mg daily16 Risperidone Psychosis 0.5mg bd (0.25–0.5mg daily in some cases)16 1–2.5mg daily15 4mg daily Late-­onset psychosis 0.5mg daily* 1mg daily* 2mg daily* (optimal dose is 1mg daily) Agitation/psychosis in dementia 0.25mg daily* or bd 0.5mg bd 2mg daily (optimal dose is 1mg daily)16 (Continued )

706 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 6 Drug Specific indication/ additional notes Starting dose Usual maintenance dose Maximum dose in elderly Haloperidol Psychosis/mania associated with bipolar disorder/delirium 0.25–0.5mg daily15 1–3.5mg daily15 Caution >3.5mg – assess tolerability and ECG   Max. 5mg/day (oral)   Max. 5mg/day (IM)   Doses >5mg/day should only be considered in patients who have tolerated higher doses and after reassessment of the patient’s individual benefit–­risk profile Agitation   Avoid in older adults (except in delirium) owing to risk of QTc prolongation. 0.25–0.5mg daily* 0.5–1.5mg daily or bd Long-­acting conventional antipsychotic drugs† Flupentixol decanoate Test dose: 5–10mg After at least 7 days of test dose: 10–20mg every 2–4 weeks*   Dose increased gradually according to response and tolerability in steps of 5–10mg every 2 weeks* 40mg every 2 weeks* (extend frequency to every 3-­–4 weeks if EPSE develop)   Occasionally up to 50 or 60mg every 2 weeks* may be used if tolerated Fluphenazine decanoate Caution – high risk of EPSE Test dose: 6.25mg After 4–7 days of test dose: 12.5–25mg every 2-­4 weeks   Dose increased gradually according to response and tolerability in steps of 12.5mg every 2–4 weeks* 50mg every 4 weeks* Haloperidol decanoate Risk of EPSE and QTc prolongation No test dose   12.5–25mg every 4 weeks 12.5–25mg every 4 weeks 50mg every 4 weeks* Pipotiazine palmitate Test dose: 5–10mg 25–100mg every 4 weeks 100mg every 4 weeks* Zuclopenthixol decanoate Test dose: 25–50mg After at least 7 days of test dose: 50–200mg every 2–4 weeks* 200mg every 2 weeks*

Prescribing in older people CHAPTER 6 Drug Specific indication/ additional notes Starting dose Usual maintenance dose Maximum dose in elderly Long-­acting atypical antipsychotic drugs† Aripiprazole (long-­acting injection24) One injection start   No detectable effect of age on pharmacokinetics24 One injection of 400mg and continue treatment with oral dose 10–20mg/day for 14 days   One injection of 300mg in frail individuals or poor metabolisers of CYP2D6 (and continue with prescribed oral dose for 14 days)   One injection of 200mg used for patients known to be CYP2D6 poor metabolisers or concomitantly use a strong CYP3A4 inhibitor (and continue with prescribed oral dose for 14 days) 400mg monthly (reduce to 300mg/ month if adverse effects)   300mg monthly in frail individuals or poor metabolisers of CYP2D6 400mg monthly (reduce to 300mg/ month if adverse effects)   300mg monthly in frail individuals or poor metabolisers of CYP2D6 Two injection start (two injection start not to be used in patients who are known to be CYP2D6 poor metabolisers and concomitantly use a strong CYP3A4 inhibitor) Two separate injections of 400mg at separate injection sites along with one 10–20mg dose of oral aripiprazole   Two injections of 300mg in frail individuals or poor metabolisers of CYP2D6 (along with one single dose of the previous prescribed dose of oral aripiprazole) 400mg monthly (reduce to 300mg/ month if adverse effects)   300mg monthly in frail individuals or poor metabolisers of CYP2D6 400mg monthly (reduce to 300mg/ month if adverse effects)   300mg monthly in frail individuals or poor metabolisers of CYP2D6 (Continued )

708 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 6 Drug Specific indication/ additional notes Starting dose Usual maintenance dose Maximum dose in elderly Olanzapine pamoate25 Has not been systematically studied in elderly patients (>65 years). Not recommended for treatment in the elderly population unless a well-­tolerated and effective dose regimen using oral olanzapine has been established. A lower starting dose (150mg/4 weeks) is not routinely indicated but should be considered for those 65 and over when clinical factors warrant. Not recommended to be started in patients >75 years. Paliperidone palmitate Dose based on renal function   Because elderly patients may have diminished renal function, they are dosed as in mild renal impairment even if tests show normal renal function.* Loading doses: day 1: 100mg day 8: 75mg (lower loading doses may be appropriate in some)* 25–100mg monthly* 100mg monthly* Paliperidone palmitate 3-­monthly injection Dose based on renal function   Because elderly patients may have diminished renal function, they are dosed as in mild renal impairment even if tests show normal renal function.* If the last dose of 1-­monthly paliperidone palmitate injectable is: 50mg 75mg 100mg Initiate the 3-­monthly injection at the following doses:   175mg 263mg 350mg   (There is no equivalent dose for the 25mg dose of 1-­monthly paliperidone palmitate injection).26 350mg 3-­monthly* Paliperidone palmitate 6-­monthly injection27 Dose based on renal function   Because elderly patients may have diminished renal function, they are dosed as in mild renal impairment even if tests show normal renal function.* Patients adequately treated with 1-­monthly paliperidone palmitate injection 100mg (preferably for 4 months or more) or 3-­monthly paliperidone palmitate injection at 350mg (for at least one injection cycle) may be transitioned to 6-­monthly paliperidone palmitate injection 700mg 700mg every 6 months*   There are no equivalent doses of 6-­monthly paliperidone palmitate for the 25, 50 or 75mg doses of 1-­monthly injection, nor for the 175 or 263 mg 3-monthly injection. 700mg every 6 months*

Prescribing in older people CHAPTER 6 Drug Specific indication/ additional notes Starting dose Usual maintenance dose Maximum dose in elderly Risperidone long-­acting injection Monitor renal function 25mg every 2 weeks 25mg every 2 weeks 25mg every 2 weeks   Consider 37.5mg every 2 weeks in patients treated with oral risperidone doses

4mg/day28 Mood stabilisers Carbamazepine Bipolar disorder   Caution – drug interactions   Check LFTs, FBC and U Es; consider checking plasma levels. 50mg bd or 100mg bd* 200–400mg/day* 600–800mg/day* Lamotrigine Bipolar disorder (titration as in young adults)   Check for interactions and make appropriate dose alterations (see BNF). 25mg daily (monotherapy) Increase by 25mg steps every 14 days 200mg/day* 25mg on alternate days (if with valproate) Increase by 25mg steps every 14 days 100mg/day* 50mg daily (if with carbamazepine) Increase by 50mg steps every 14 days 100mg bd* Lithium carbonate modified release Bipolar disorder   Mania/depression   Caution – drug interactions   Check renal and thyroid function and regularly monitor plasma levels. 100–200mg nocte* 200–600mg daily* 600–1200mg daily (aim for plasma levels 0.4–0.7mmol/L in elderly)29 Sodium valproate Bipolar disorder   Check LFTs and consider checking plasma levels. Sodium valproate: 100–200mg bd*   Semi-­sodium valproate: 250mg daily or bd* Sodium valproate: 200–400mg bd*   Semi-­sodium valproate: 500mg to 1g daily* Sodium valproate: 400mg bd*   Semi-­sodium valproate: 1g daily* Agitation in dementia (not licensed and not recommended)   Check response, tolerability and plasma levels for guide. Sodium valproate: 50mg bd (liquid) or 100mg bd* Sodium valproate: 100–200mg bd* Sodium valproate: 200mg bd* (Continued )

710 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 6 Drug Specific indication/ additional notes Starting dose Usual maintenance dose Maximum dose in elderly Anxiolytics/hypnotics Clonazepam Agitation 0.5mg daily 1–2mg/day* 4mg/day* Daridorexant30 Insomnia   Taken within 30 minutes before going to bed, with at least 7 hours remaining prior to planned awakening 25mg nocte 25–50mg nocte 50mg nocte Diazepam Agitation 1mg tds 1mg tds* 7.5–15mg/day in divided doses (for anxiety) Lemborexant31 Insomnia 5mg nocte (take no more than once per night, immediately before bed) 5–10mg nocte 10mg nocte   Elderly are at a higher risk of falls. Caution when using doses >5mg in patients ≥65 years old   The maximum recommended dose is 5mg nocte when co-­administered with weak CYP3A inhibitors or in moderate hepatic impairment (avoid in severe hepatic impairment). Lorazepam PRN only – avoid regular use due to short half-­life and risk of dependence 0.5mg daily 0.5–2mg daily* 2mg/day Melatonin Insomnia – short-term use (up to 13 weeks) 2mg (modified release) once daily (1–2 hours before bedtime) 2mg once daily Occasionally 10mg/day (modified release) has been used successfully in dementia Pregabalin Generalised anxiety disorder   Dose adjustment based on renal function (see product information)32 Usually 25mg bd (increase by 25mg bd weekly)   Up to 75mg bd (if healthy and normal renal function) Usually 150mg daily*   Up to 150mg bd (if healthy and normal renal function) 150–300mg/day*