41 - Specific antipsychotics

Specific antipsychotics

Bipolar disorder CHAPTER 2 Bipolar depression In acute treatment of bipolar depression, antipsychotics found to be effective include cariprazine, lumateperone, lurasidone, olanzapine (± fluoxetine) and quetiapine.14,19,20 In terms of mechanism, this does not appear to be a dopamine-­mediated effect as aripiprazole and most dopamine-­blocking antipsychotics do not show efficacy in acute bipolar depression.19 Efficacy is similar among those shown to be effective, although lurasidone may be superior to cariprazine.21,22 Maintenance Compounds that have efficacy in the acute phase of bipolar disorder, whether that be mania or depression, seem to exert effects in maintenance treatment.23 This is borne out by a network meta-­analysis of maintenance treatments in bipolar disorder, in which olanzapine, quetiapine and risperidone LAIs showed effects against relapse.24 This analysis did not include more recent (positive) trials of aripiprazole (see next section),24 nor studies of cariprazine25 which may not be effective as maintenance treatment. Specific antipsychotics Aripiprazole Aripiprazole is effective in acute treatment of mania both alone,26–­28 as an add-­on agent29 and in long-­term prophylaxis.30,31 No difference is seen when directly compared with lithium or haloperidol although one small RCT suggested lithium was more effective in mania.32 In trials in mania, aripiprazole is associated with nausea and movement disorder (mainly akathisia).33 Aripiprazole LAI is also effective for prophylaxis in bipolar I disorder with the effect predominantly on prevention of manic episodes.34 Asenapine Asenapine is given by the sublingual route and is effective in mania.35,36 Efficacy seems to be maintained in the longer term,37 with RCT evidence showing efficacy in preventing depression and manic episodes in people with bipolar I disorder.38 Asenapine is less likely to cause weight gain and metabolic disturbance39 than some other antipsychotics. Cariprazine Cariprazine is efficacious for treating mania as well as depression symptoms in people with mania with mixed features40 and has a low propensity for weight gain.39 Clozapine The earliest observational study of antipsychotics for maintenance treatment in bipolar disorder examined clozapine in people attending a service for resistant mood disorders.41 There is evidence from at least 15 trials to suggest improvements in treatment-­resistant bipolar disorder (TRBD) (where two treatments have failed,

302 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 2 despite adequate dose and duration) and in depression, mania, rapid-cycling states and psychotic symptoms.42 Clozapine is fairly widely used in bipolar disorder, particularly in South-­East Asia.43 Lurasidone Lurasidone is licensed by the FDA as monotherapy and adjunctive treatment to lithium and divalproex for acute treatment of bipolar depression, on the basis of RCTs of monotherapy versus placebo,44 and as an adjunct to lithium or valproate.45 The main adverse effects include nausea and akathisia, with minimal effects on weight and metabolic parameters.39 Olanzapine Olanzapine is effective in mania.46,47 As with other FGAs, olanzapine is most effective when used in combination with a mood stabiliser in acute mania and for symptomatic (though not syndromal) relapse prevention,48,49 although in one study, olanzapine + carbamazepine was no better than carbamazepine alone.50 Data suggest olanzapine may offer benefits in longer-term treatment.51,52 It may be more effective than lithium.53,54 Olanzapine is, of course, associated with significant metabolic effects, including weight gain, effects that are minimised by the use of the olanzapine/samidorphan combination available in some countries.55,56 Quetiapine Data relating to quetiapine57–­59 suggest robust efficacy in all aspects of bipolar disorder including prevention of mania and bipolar depression.60 It has low propensity for extrapyramidal side effects (EPSEs), though there are significant effects on weight and metabolic parameters. Risperidone Risperidone has shown efficacy in mania,61 particularly in combination with a mood ­stabiliser.62,63 Risperidone LAI (as Risperdal Consta) is also effective64 (note though that the pharmacokinetics of this formulation generally render it an unsuitable choice for the acute treatment of mania). The long-­acting version is used as prophylaxis (an unlicensed use in most countries). It is effective as prophylaxis against mania in the longer term.23 Paliperidone can be assumed to have similar effects, although prospective, controlled data are lacking.65 Other antipsychotics There are few data for amisulpride66 and rather more for ziprasidone,67 which is sometimes used for mania in the USA. Iloperidone may be effective in mixed episodes68 but data are insufficient to support its use. Lumateperone is effective in bipolar depression.69,70