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

Objectives To provide an update on the pharmacologic treatment options for bipolar disorder with a focus on the role of antipsychotics. Methods Selective review of efficacy and tolerability data of acute and maintenance treatments for bipolar mania and bipolar depression, as monotherapy and in combination, supplemented by a discussion of differences in psychopharmacological profiles of antipsychotics with relevance for clinical switching and dosing paradigms. 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 olanzapine-fluoxetine. 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. Conclusions There has been a paradigm shift, in that antipsychotics are not merely adjunctive treatments during an acute, psychotic mania episode, but data support the routine use of atypical antipsychotics for the acute treatment of mania and maintenance treatment of bipolar disorder. Combination treatments have the chance of improving outcomes. More data and agents are needed to effectively treat bipolar depression, and important methodological effects of dosing and changes in specific symptom domains need to be addressed in future trials.