40 - Second generation antipsychotics

Second-generation antipsychotics

300 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 2 Antipsychotic drugs in bipolar disorder Antipsychotic drugs not only have activity that reduces psychotic symptoms,1 ­individual antipsychotics variously possess sedative, anxiolytic, anti-­manic, mood-­stabilising and antidepressant properties. Some antipsychotics (quetiapine and olanzapine) show all of these activities. Antipsychotics licensed by the US Food and Drug Administration (FDA) for use in bipolar disorder include aripiprazole (mania, mixed episodes, maintenance treatment), asenapine (mania, mixed states), cariprazine and lumateperone (bipolar depression), lurasidone (bipolar depression), olanzapine (mania, mixed episodes, maintenance), olanzapine and fluoxetine (bipolar depression), quetiapine (mania, maintenance, bipolar depression), risperidone (mania, mixed episodes) and ziprasidone (mania, maintenance). Risperidone LAI has been approved for monotherapy or adjunctive maintenance, and aripiprazole depot for monotherapy maintenance treatment. EU labelling is similar except that olanzapine/fluoxetine in combination is not licensed for any indication and no second-­generation antipsychotic (SGA) long-­acting injection (LAI) has a licence for maintenance. First-­generation antipsychotics These agents have long been used in mania and several studies support their use in the acute phase of illness, with superiority over placebo and comparable effects to lithium.2,3 Their effectiveness is enhanced by combination with lithium.4,5 In the longer­ term maintenance treatment of bipolar disorder, first-­generation antipsychotics (FGAs) are widely used6 but modern, robust supporting data are absent.7 FGAs are relatively more often associated with both depression and tardive dyskinesia in bipolar ­disorder7–­9 and their use is declining. The higher rate of tardive dyskinesia with FGAs is not in doubt, but the greater risk of depression,10,11 while less well supported, is certainly worthy of consideration. Second-­generation antipsychotics Mania Network meta-­analyses indicate superiority of antipsychotics over placebo in mania, with similar activity to so-­called mood stabilisers.12–­14 In a 2023 network meta-­analysis, efficacy of individual antipsychotics was broadly similar,15 with a suggestion of superiority of risperidone. Adjunctive treatment with antipsychotics is more effective than monotherapy with mood stabiliser medication, and augmentation with mood stabiliser medication is more effective than antipsychotic monotherapy. The combination is associated with more adverse effects, especially somnolence.16 Interpretation of outcomes is made difficult by trials including patients whose mania occurred in the context of failed mood stabiliser treatment. Participants receive either a failed mood stabiliser or a mood stabiliser plus an antipsychotic. The superior effect of the combination is not surprising in this context. Although the mechanism is difficult to discern, converging evidence suggests anti-­ manic effects of antipsychotics are related to their effects on the dopamine system.17,18