Antipsychotic augmentation for major depressive disorder: A review of clinical practice guidelines

Abstract

Clinical Practice Guidelines (CPGs) are seen as the gold standard of evidence-based care. Because of their influence, these guidelines can have profound legal and economic effects. Despite their proliferation and influence, the trustworthiness and quality of guidelines have been seriously questioned and they have been implicated as drivers of overtreatment. In the U.S, augmentation with second generation antipsychotics (SGAs) is becoming an increasingly common strategy for treating major depressive disorder (MDD) when initial antidepressant treatment does not result in remission of symptoms. However, there is debate about the evidence for augmentation and whether this strategy is a form of overtreatment. We conducted a systematic search to identify treatment guidelines for MDD. Fourteen international guidelines met inclusion criteria and we reviewed them to determine: 1) if augmentation with SGAs was recommended for patients who did not respond to antidepressant medication; 2) what evidence was cited for the recommendation for or against augmentation; 3) the extent to which the guidelines addressed risk/benefit concerns when making their recommendations. There was significant variation among the CPGs regarding the recommendation to augment with antipsychotic medication for Major Depressive Disorder. Seven guidelines explicitly recommended augmentation with antipsychotics; 1 guideline reviewed the evidence but neither recommended for nor against; 1 guideline did not make a clear recommendation; 2 guidelines explicitly recommended against augmentation; and 3 guidelines did not address augmentation with antipsychotics as a potential treatment strategy. There was wide variation in terms of attention to risk/benefit issues and to the conditions under which augmentation should be considered. The results are discussed in terms of the implications for risk management and informed consent practices.

Keywords: Antipsychotic; Augmentation strategy; Clinical practice guideline; Informed consent; Major depressive disorder; Treatment resistant depression.