02 - Drug treatments of BPD

Drug treatments of BPD

788 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 9 In 2009 the UK National Institute for Health and Care Excellence (NICE)8 ­recommended that: ■ ■Drug treatment should not be used routinely for BPD or for the individual symptoms or behaviour associated with the disorder (e.g. repeated self-­harm, marked emotional instability, risk-­taking behaviour and transient psychotic symptoms). ■ ■Drug treatment may be considered in the overall treatment of comorbid conditions. ■ ■Short-­term use of sedative medication may be considered as part of the overall treatment plan for people with BPD in a crisis. The duration of treatment should be agreed with the patient but should be no longer than 1 week. Owing to changes in the latest revision of ICD-­11, which now defines all personality disorders as a single condition classified by severity, the current UK NICE guidelines are under review.8 A number of systematic reviews have been completed since the initial publication of the NICE guideline, concluding that evidence does not support the use of medicines alone, although when coupled with psychotherapy significant improvements in mood and behaviour can be anticipated.9,10 A 2022 Cochrane review11 concluded that medication has little or no effect on BPD symptom severity, self-­harm, suicide-­related outcomes and psychosocial functioning compared with placebo but may slightly reduce interpersonal problems. However, the evidence considered by the Cochrane review was rated as very low or low certainty and reporting on adverse events was poor and mostly non-­standardised. It is clear that further research of good quality is required in this area. Drug treatments of BPD Antipsychotics A systematic review of RCTs evaluating the efficacy of second-­generation antipsychotics (SGAs) in a number of aspects of BPD found that there was no overall improvement in BPD or in functioning.10 A beneficial effect of aripiprazole on anger and of quetiapine on aggression were shown, but a number of trials were rated as having moderate or high risk of bias and most of the evidence was deemed to be of low certainty.10 Olanzapine may have the best supported effectiveness in treating some BPD symptoms, along with depressive and anxiety symptoms, although it has not been shown to improve self-­harm or aggression.10 Furthermore, olanzapine’s propensity for inducing metabolic syndrome means that patients must be fully informed of the risks of this before commencing off-­label treatment with this agent and it should only be considered an option of ‘last resort’ for individuals with distressing symptoms that cannot be managed psychologically. Quetiapine is perhaps the most widely used antipsychotic in BPD. Its use is supported by small studies that reported modest improvement in a number of symptoms, but not impulsivity.12,13 In general, SGAs appear to improve general psychopathology, although this may be a reflection of improvement in comorbid conditions. There is some evidence to support the use of clozapine to improve psychotic symptoms, aggression, impulsivity, self-­harming behaviour and overall functioning (with associated reduced hospital use) in those with severe treatment-­refractory BPD, high suicide risk and frequent hospitalisations.9,14 A placebo-­controlled RCT of lumateperone is underway at the time of writing.15

Drug treatment of other psychiatric conditions CHAPTER 9 Antidepressants Several open studies and small RCTs have investigated the use of selective serotonin reuptake inhibitors (SSRIs), ­serotonin–­noradrenaline reuptake inhibitors (SNRIs) and flupentixol in BPD. Fluoxetine has been noted to improve symptoms of BPD including impulsivity, self-­harm, anger and mood instability, but one RCT comparing DBT or supportive therapy alone or in combination with fluoxetine showed higher rates of suicide attempts in those given fluoxetine.16 Duloxetine has been reported to improve overall psychopathology, depression, impulsivity and affective dysregulation17 and venlafaxine reduced somatic symptoms and self-­injurious behaviour.18 In an open study, antidepressant doses of flupentixol showed significant improvements in general psychopathology and impulsivity symptoms but no further studies have been published to confirm this effect.9,19 Lastly, in a large database review of patients with BPD, bupropion decreased the risk of psychiatric re-­hospitalisation.20 Overall, evidence supporting the use of antidepressants is weak and any beneficial effects are modest at best. Mood stabilisers and anticonvulsants There is some evidence in BPD that valproate and topiramate may improve anger.10 Valproate may reduce aggression and irritability and gabapentin may improve anxiety, affective instability and depressive symptoms.9 Obviously, given the risk of teratogenicity associated with valproate, it should never be prescribed to people of child-­bearing age. Lithium is licensed for the control of aggressive behaviour or intentional self-­harm, although its use in BPD has declined owing to concerns over long-­ term toxicity.21 Small studies have suggested lamotrigine may improve anger and reduce aggression, impulsivity and affective lability, though a large RCT found it had no effect at all on any symptom domain.9,10 Carbamazepine9 and mifepristone are likewise ineffective.22 Lisdexamfetamine and methylphenidate In a large database review of patients with BPD, lisdexamfetamine and methylphenidate decreased the risk of all hospitalisations, death and psychiatric re-hospitalisation.20 This probably reflects prescribing for attention deficit hyperactivity disorder (ADHD) in the context of BPD. Memantine An RCT of 33 subjects found adjunctive memantine 20mg a day to be more effective than placebo and well tolerated. More trials are needed.9 Opioid antagonists Very limited evidence supports the efficacy of naltrexone in reducing dissociative symptoms, but there have been no definitive trials supporting the effectiveness of naltrexone in the treatment of patients with BPD.9