Adjunctive Atypical Antipsychotics in Major Depressive Disorder: A Network Meta-Analysis Perspective and Consensus...

Objective: The goal of this consensus panel was to generate expert perspectives on the comparative efficacy, safety, tolerability, and clinical relevance of FDA-approved adjunctive atypical antipsychotics for adults with major depressive disorder (MDD) and inadequate response to antidepressant therapy.

Participants: Five academic and clinical experts in psychiatry and psychopharmacology participated as panelists: Roger S. McIntyre, Andrew J. Cutler, Christoph U. Correll, Joseph F. Goldberg, and Stephen M. Stahl. The discussion was conducted as a closed expert panel.

Evidence: The panel primarily discussed research findings from two recent network meta-analyses (NMAs) evaluating approved adjunctive atypical antipsychotics in MDD, supplemented by relevant published literature and panel expertise. The NMAs differed in study inclusion, treatment-node definitions, and analytical approaches to examine efficacy, acceptability, and safety. Panel discussion was used to contextualize the findings and address their clinical applicability and limitations.

Consensus Process: The panel reviewed and discussed the NMA methodology, comparative efficacy and safety outcomes, effect modifiers, and implications for shared decision-making. The consensus manuscript was developed from the panel discussion and evidence review, with subsequent expert review and incorporation of relevant comments and revisions.

Conclusions: The panel concluded that the two NMAs provide complementary and broadly concordant comparative evidence that can inform clinical decision-making. Treatment selection should integrate efficacy with tolerability, patient characteristics, preferences, and practical considerations. The panel emphasized earlier consideration of effective, FDA-approved adjunctive treatment when appropriate, while recognizing remaining relevant gaps in long-term, head-to-head, and phenotype-specific evidence. The panel did not endorse any particular agent.