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This systematic review and network meta-analysis compared five FDA-approved atypical antipsychotics used adjunctively in major depressive disorder. Twenty-two short-term studies involving 10,962 participants were analyzed: aripiprazole (n=1,297), brexpiprazole (n=1,973), cariprazine (n=1,894), lumateperone (n=483), quetiapine XR (n=719), and placebo (n=4,596). For ≥50% reduction in MADRS scores, lumateperone showed RR 1.72 (95% CrI 1.40–2.15), followed by aripiprazole 1.53 (1.32–1.77), brexpiprazole 1.38 (1.18–1.65), cariprazine 1.20 (1.07–1.36), and quetiapine XR 1.15 (0.96–1.35). For acceptability, assessed by all-cause discontinuation, aripiprazole had RR 1.16 (0.89–1.50), while lumateperone had RR 2.30 (1.45–3.84). The analysis also examined symptomatic remission and clinically significant weight gain. The authors emphasize differences across agents in efficacy, acceptability, and tolerability, while noting limited evidence for maintenance efficacy.
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This systematic review and network meta-analysis compared five FDA-approved atypical antipsychotics used adjunctively in major depressive disorder. Twenty-two short-term studies involving 10,962 participants were analyzed: aripiprazole (n=1,297), brexpiprazole (n=1,973), cariprazine (n=1,894), lumateperone (n=483), quetiapine XR (n=719), and placebo (n=4,596). For ≥50% reduction in MADRS scores, lumateperone showed RR 1.72 (95% CrI 1.40–2.15), followed by aripiprazole 1.53 (1.32–1.77), brexpiprazole 1.38 (1.18–1.65), cariprazine 1.20 (1.07–1.36), and quetiapine XR 1.15 (0.96–1.35). For acceptability, assessed by all-cause discontinuation, aripiprazole had RR 1.16 (0.89–1.50), while lumateperone had RR 2.30 (1.45–3.84). The analysis also examined symptomatic remission and clinically significant weight gain. The authors emphasize differences across agents in efficacy, acceptability, and tolerability, while noting limited evidence for maintenance efficacy.
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