Evidence Lacking for Pharmacotherapy for Common Symptoms of Bipolar Disorder

Picture of various multicolored pills
Picture of various multicolored pills
Investigators conducted a systematic review and meta-analysis to assess the effect of pharmacotherapy on anxiety symptoms in individuals with bipolar disorder.

Researchers conducting a systematic review and meta-analysis identified the need for further research into pharmacotherapies for patients with bipolar disorder in order to address other associated symptoms, such as anxiety. These findings were published in Bipolar Disorders.

A team of investigators from the University of Toronto in Canada and Max-Planck Institute of Psychiatry in Germany searched publication databases through July 2020 for studies of pharmacotherapy for anxiety, depression, or mania among patients with bipolar disorder. A total of 37 randomized clinical trials met the study inclusion criteria for the systematic review and 17 for the meta-analysis.

Overall, the investigators reported mixed results among all studies, with some trials finding significant improvement with pharmacotherapy for anxiety and depression symptoms and others finding no difference compared with placebo.

For the studies of anxiety (n=13 trials; n=2175 participants), a small significant effect was reported (standardized mean difference [SMD], -0.22; 95% CI, -0.34 to -0.11; I2, 26%). Stratified by patient features, there was a significant effect observed for symptom severity, in which there was higher efficacy among patients with higher severity (P =.007) and for patients with co-occurring depression (P =.046).

For studies of depression (n=16 trials; n=2511 participants), medications were observed to have a modest effect (SMD, -0.21; 95% CI, -0.39 to -0.03; I2, 72%).

The studies that assessed mania or hypomania (n=10 trials; n=1309 participants) reported no significant effect compared with placebo (SMD, -0.12; 95% CI, -0.28 to 0.03; I2, 36%).

Overall, there was little evidence of all-cause discontinuation differences between active and placebo treatments (odds ratio [OR], 0.98; 95% CI, 0.91-1.06).

This study was limited by the variation in medications and dosing used for the treatment of anxiety, depression, and mania.

The study authors concluded that due to the conflicting findings and overall low effect sizes for symptom improvement from atypical antipsychotics, there was a paucity of data to support the use of these pharmacotherapies for treating common symptoms associated with bipolar disorder. Therefore, additional studies are needed to address long-term symptoms of anxiety among many patients with bipolar disorder.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Cullen C, Kappelmann N, Umer M, et al. Efficacy and acceptability of pharmacotherapy for comorbid anxiety symptoms in bipolar disorder: A systematic review and meta-analysis. Bipolar Disord. Published online September 10, 2021. doi:10.1111/bdi.13125