Background: First-generation antipsychotics have been the treatment of choice for acute mania with or without psychosis. However, because these agents may cause severe side effects and may worsen depressive symptoms in patients with bipolar disorder, they have limited use in these patients. Second-generation antipsychotics developed over the past few years have proven to be effective in the treatment of acute mania in bipolar disorder. These medications cause fewer side effects than the first-generation agents, do not appear to induce depressive episodes, and may have some antidepressant effect. One recent study found that there is significant variation in practice patterns when treating acute mania in bipolar disorder. To answer concerns about the effectiveness and safety of second-generation antipsychotics for this indication, Scherk and colleagues performed a meta-analysis of published randomized controlled trials.

The Study: The authors searched the PsiTri and Medline databases for published and unpublished randomized controlled trials evaluating the effectiveness of second-generation antipsychotics in the treatment of acute mania in bipolar disorder. (PsiTri registers controlled trials that compile the published studies for the mental health field from all Cochrane review groups.) The second-generation antipsychotics included aripiprazole (Abilify), clozapine (Clozaril), olanzapine (Zyprexa), quetiapine (Seroquel), risperidone (Risperdal), ziprasidone (Geodon), and zotepine (Zoleptil). The primary outcome extracted from the literature was the mean change in the Young Mania Rating Scale score or similar scale scores from baseline to end point. Other outcome measures were response rate, effectiveness criteria (e.g., rates of dropout because of side effects or lack of effect), weight gain, rate of somnolence, and extrapyramidal symptoms.

Results: Twenty-four studies met the inclusion criteria, with a total of 6,187 patients. The studies compared second-generation antipsychotics with placebo, mood stabilizers, placebo in addition to mood stabilizers, or haloperidol (Haldol). Second-generation antipsychotics were significantly more effective than placebo and had effectivity similar to that of mood stabilizers. Participants who received the combination of second-generation antipsychotic and mood stabilizers had better response than those who were treated with only a mood stabilizer. Response rates for second-generation antipsychotics and haloperidol were similar. With regard to side effects, some second-generation antipsychotics were associated with an increased risk of extrapyramidal symptoms and somnolence compared with placebo.

Conclusion: Published data suggest that second-generation antipsychotics in addition to mood stabilizers are the best treatment strategy for acute mania. This combination resulted in greater reduction in mania scores, better response rates, and fewer dropouts resulting from ineffective treatment.