Clinical Practice Guidelines Inconsistent Regarding Antipsychotic Augmentation for Major Depression

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The guidelines were reviewed for augmentation with antipsychotics in treatment-resistant depression, evidence to support when to/not to use antipsychotics for augmentation, and the risks/benefits when choosing antipsychotics.

In a study published in the International Journal of Law and Psychiatry, researchers evaluated existing Clinical Practice Guidelines (CPGs) regarding treatment augmentation with second generation antipsychotics (SGAs) in patients with major depressive disorder (MDD). The findings revealed a lack of consensus among CPGs and indicated that SGAs should be prescribed cautiously to manage risks and avoid overtreatment.

Researchers utilized the MEDLINE search engine and the International Guideline Library to identify and evaluate 14 existing guidelines for MDD treatment. Of these, 7 guidelines explicitly recommended augmentation with SGAs for treatment-resistant depression, 2 explicitly recommended against augmentation, and the remaining guidelines either made no clear recommendation or did not address augmentation. 

Of the 7 guidelines recommending augmentation, only 4 cited meta-analyses regarding the efficacy and safety of antipsychotics as support for their suggestions. Across these 7 guidelines, there was also wide variation in terms of augmentation timeline and attention to risk/benefit issues, with not one guideline addressing the issue of tapering or timeline to discontinuation of SGA use. In addition, in several guidelines recommending SGA use, the researchers explicitly acknowledged the unclear evidence base supporting the effectiveness of SGAs, but proceeded to recommend augmentation despite this.

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Given the inconsistencies across CPGs recommending SGA use, researchers implored physicians to cautiously approach treatment augmentation on a case-by-case basis. They underscored the well-documented side effects and potential risks of SGAs, and emphasized the importance of informed consent in discussing treatment options with patients.


Simons P, Cosgrove L, Shaughnessy A, Bursztajn H. Antipsychotic augmentation for major depressive disorder: A review of clinical practice guidelines. Int J Law Psychiatry. 2017;55:64-71.