Second generation antipsychotics in the treatment of bipolar depression: a systematic review and meta-analysis

Depressive symptoms and episodes dominate the course of bipolar disorder. However, the therapeutic armamentarium for bipolar depression is limited. Recent evidence points to the efficacy of second generation antipsychotics (SGAs) for the treatment of bipolar depression. We conducted a systematic review and meta-analysis of the efficacy and safety of SGAs (randomized, double-blind, placebo-controlled trials; used in monotherapy) in the treatment of adult patients with bipolar depression. Publication bias was corrected for by performing similar searches using the clinical trials register of the respective pharmaceutical companies, the Cochrane Database and ClinicalTrials.gov. Seven published papers were identified on the use of aripiprazole, olanzapine and quetiapine. Internal validity of the trials was fairly good, external validity only moderate. Different outcome measures of efficacy and safety were assessed. When the individual trials were looked at, quetiapine and to a lesser extent olanzapine demonstrated significant improvement in MADRS (Montgomery-Asberg Depression Rating Scale) total scores. This was not demonstrated for aripiprazole. Efficacy was hampered by adverse events, such as weight gain, akathisia and somnolence/sedation. Both clinical heterogeneity of the included trials and statistical heterogeneity of the meta-analytic data were considerable. The number of quetiapine trials was disproportionate to the number of trials of aripiprazole and olanzapine. Further research is needed to assess differential efficacy of the different SGAs and their use in clinical practice.