Antipsychotic Medications for Depression: Symptoms and Quality of Life

March 13, 2013
antipsychotic medications

A meta-analysis of trials of antipsychotic medications suggests that although antipsychotics are linked with small-to-moderate improvement in symptoms of depression, they do not seem to improve patients’ quality of life. Glen I. Spielmans, PhD, of Metropolitan State University in St. Paul, and colleagues published their findings in the online March PLOS Medicine. 

The researchers compared adjunctive antipsychotic medications (aripiprazole, olanzapine/fluoxetine combination, quetiapine, and risperidone) to placebo in 14 randomized, controlled trials of participants with depression that did not respond antidepressant medication alone. 

Results showed that all four of the antipsychotic medications produced statistically significant benefits in relation to remission of depressive symptoms, and all except for the olanzapine/fluoxetine combination significantly improved response rates. 

However, the medications were not effective at improving quality of life. Risperidone produced a small-to-moderate effect on quality of life, but the rest of the medications led to either no benefit or a very small benefit. 

Adverse effects were common, noted the investigators, and included akathisia, sedation, and abnormal metabolic laboratory results. All four of the medications were associated with weight gain. 

The study authors cautioned that shortcomings in the study design and methods of data reporting could have exaggerated the benefits of treatment and reduced the apparent incidence of adverse events. 

“This evaluation of the safety and efficacy of adjunctive treatments for clinical depression provides critical insights that should help clinicians better understand the risk–benefit profiles of this approach to the treatment of major depressive disorder,” the researchers stated.


—Lauren LeBano



1. Spielmans GI, Berman MI, Linardatos E, et al. Adjunctive atypical antipsychotic treatment for major depressive dsorder: A meta-analysis of depression, quality of life, and safety outcomes. PLOS Medicine. 12 March 2013;[Epub ahead of print].

2. Use of adjunctive antipsychotic medications in depression [press release]. Washington, DC: EurekAlert; March 12, 2013.