The role of antipsychotics and mood stabilizers in the treatment of bipolar disorder

Results In a recent meta-analysis, efficacy for mania compared to placebo was demonstrated for all studied antipsychotics, lithium and selected antiepileptic medications, such as carbamazepine and valproic acid. Conversely, lamotrigine and topiramate were not superior to placebo. The pooled effect sizes of the agents separating from placebo ranged from 0.23 (small) to 0.66 (moderate), with overlapping 95% confidence intervals, indicating no significant differences in their efficacy vs. placebo in this indirect comparison. In head to head trials, when pooling results from multiple studies, antipsychotics were associated with a somewhat faster speed of onset and/or modestly greater efficacy than antiepileptics or lithium. While a class effect for antidopaminergic agents, but not anticonvulsants was observed for the treatment of mania, no class effect for either medication group was apparent for bipolar depression, for which the most robust results were found with quetiapine and olanzapinefluoxetine. Combining antipsychotics with conventional mood stabilizers was associated with faster and more profound symptom improvement compared to conventional mood stabilizer monotherapy. Finally, all agents shown to be effective for mania as well as lamotrigine were more effective than placebo for preventing mood episodes, but agents differed regarding the strength of the effect for preventing mania or depression. In addition, treatments for bipolar disorder differed regarding their adverse effects, influencing overall effectiveness. Switching from a higher metabolic risk antipsychotic to one with lower metabolic risk was shown to substantially improve metabolic health, but pharmacologically informed switching can improve switch success by minimizing potential withdrawal and rebound phenomena.