The treatment of acute mania in bipolar disorder presents a unique challenge for healthcare professionals today due to insufficient comparative data on antimanic agents. Few studies directly compare the efficacy and tolerability of the well-established first-line treatment options for acute mania, antipsychotics and mood stabilizers.1-3 Therefore, selection of a preferred treatment remains ambiguous. Current guidelines consider mood stabilizers and antipsychotics reasonable first-line treatments; however, it is unclear which agent may provide superior efficacy.4 A recent meta-analysis published in Lancet in August 2011 aimed to compare the effectiveness and acceptability of currently utilized antimanic agents in the treatment of acute mania.5
The multiple-treatments meta-analysis reviewed 68 randomized controlled trials published in the last 30 years, including both head-to-head comparative antimanic trials and placebo-controlled antimanic trials. The authors required all trials to be a minimum of 3 weeks in duration. Primary outcomes assessed included efficacy, measured by the mean change in Young Mania Rating Scale (YMRS) scores, and tolerability, based on treatment discontinuation for any reason. A secondary analysis was conducted to evaluate the percentage of patients responding to treatment. Antipsychotics evaluated in the meta-analysis included aripiprazole, asenapine, haloperidol, olanzapine, quetiapine, risperidone, and ziprasidone. The mood stabilizers assessed included carbamazepine, gabapentin, haloperidol, lamotrigine, lithium, topiramate, and valproate.
Over 16,000 patients were included in the meta-analysis. Haloperidol, risperidone, olanzapine, lithium, quetiapine, aripiprazole, carbamazepine, asenapine, valproate, and ziprasidone were found to be significantly more effective than placebo, while gabapentin, topiramate, and lamotrigine did not demonstrate superiority over placebo. Haloperidol, risperidone, and olanzapine exhibited the greatest efficacy compared to the active comparators, and olanzapine, risperidone and quetiapine were associated with lower treatment discontinuation rates compared to placebo. The authors concluded that antipsychotics were significantly more effective than mood stabilizers in the treatment of acute mania in bipolar disorder. Furthermore, risperidone, olanzapine, and haloperidol were found to be the best available options in terms of efficacy and tolerability (based on study dropouts) for the treatment of acute mania; however, haloperidol demonstrated slightly less tolerability than risperidone and olanzapine.
While the meta-analysis provides support for treating acute mania with antipsychotics, specifically risperidone, olanzapine, and haloperidol, the study was not without limitations. Most of the trials included were short in duration, approximately 3 weeks, limiting the data’s application to the short-term treatment of mania only. The majority of trials were performed in inpatient facilities allowing the results to be applied to patients hospitalized for acute manic episodes; however, patients with more severe mania were excluded from the analysis, as informed consent was required prior to enrolling subjects in these studies. In addition, the authors reported treatment discontinuation as an indirect measure of tolerability, while patient side effects, daily functioning, and quality of life were not specifically described. The short treatment duration may have minimized the long-term metabolic effects of second-generation antipsychotics, which possibly influence the tolerability of these agents later in treatment. Also, the study failed to report dosing regimens perhaps impacting study results if sub-therapeutic doses ...