News Release

Use of adjunctive antipsychotic medications in depression

Press release from PLOS Medicine

Peer-Reviewed Publication


A study published this week in PLOS Medicine finds that while antipsychotic medications are associated with small-to-moderate improvements in depressive symptoms in adults, there is little evidence for improvement on measures of quality of life and these medications are linked to adverse events such as weight gain and sedation.

The results of the study, conducted by Glen Spielmans of Metropolitan State University in St. Paul, Minnesota and colleagues, have potential implications for the treatment of depression by providing clinicians with a better understanding of the risk–benefit profiles for commonly prescribed antipsychotic medications.

The authors reached these conclusions by combining the results from 14 published or unpublished randomized clinical trials (duration 4-12 weeks) comparing an adjunctive antipsychotic medication (aripiprazole, olanzapine/fluoxetine combination [OFC], quetiapine, or risperidone) to placebo in the treatment of depression that had not responded to antidepressant medication alone.

The four medications showed statistically significant small or small-to-moderate beneficial effects on depression symptoms. However, on measures of functioning and quality of life, these medications generally produced either no benefit or small benefits. In addition, treatment was linked to several adverse events, such as akathisia, sedation, abnormal metabolic laboratory results, and weight gain. The authors also comment that shortcomings in study design and reporting may have over-emphasized the apparent benefits of treatment and reduced the apparent incidence of adverse events.

The authors say: "Taken together, our meta-analysis found evidence of (1) some improvement in clinician-assessed depressive symptoms, (2) little evidence of substantial benefit in overall well-being, and (3) abundant evidence of potential treatment-related harm."

They add: "Our comprehensive evaluation of safety and both relative and absolute efficacy provides critical insight that may be useful for clinicians attempting to thoroughly understand the risk–benefit profiles of these adjunctive treatments for major depressive disorder."

Individuals treated with adjunctive antipsychotic medication who are concerned about potential side effects are urged to discuss this study with their physician before making any decisions to stop taking or change any medications.


Funding: ACT acknowledges salary support through Mentored Patient-Oriented Research Career Development Award K23 MH-096620, US National Institute of Mental Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: GIS is a member of Healthy Skepticism and holds shares of less than $10,000 in a mutual fund (Vanguard Health Care) that invests heavily in pharmaceutical firms. NZR is a member of both the National Physicians Alliance and Healthy Skepticism. NZR is also a local site investigator on a Department of Veterans Affairs sponsored multi-site trial of treatments for resistant depression. One study arm is receiving aripiprazole augmentation. The study is receiving no funding from pharmaceutical companies. NZR is also serving as a consultant in a lawsuit against the manufacturer of aripiprazole. ACT acknowledges salary support through Mentored Patient-Oriented Research Career Development Award K23 MH-096620, US National Institute of Mental Health. ACT is a former board member of the ethics committee, and former member, of the National Physicians Alliance. GIS had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. No specific funding was provided to support the conduct of this meta-analysis. The authors declare no other competing interests.

Citation: Spielmans GI, Berman MI, Linardatos E, Rosenlicht NZ, Perry A, et al. (2013) Adjunctive Atypical Antipsychotic Treatment for Major Depressive Disorder: A Meta-Analysis of Depression, Quality of Life, and Safety Outcomes. PLoS Med 10(3): e1001403. doi:10.1371/journal.pmed.1001403



Glen I. Spielmans
Department of Psychology
Metropolitan State University
St. Paul, Minnesota, United States of America,

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