Use of adjunctive antipsychotic medications in depression

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The authors reached these conclusions by combining the results from 14 published or unpublished randomized clinical trials (duration 4-12 weeks) comparing an adjunctive antipsychotic medication (aripiprazole, olanzapine/fluoxetine combination [OFC],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.