First Network Meta-Analysis Compares Efficacy and Safety of MDD Adjunctive Therapies

In "First Network Meta-Analysis Compares Efficacy and Safety of MDD Add-On Therapies," Dr. Citrome turns to a network meta-analysis he co-authored, breaking down its data in detail.

Dr. Citrome discusses a network meta-analysis he co-authored, published this year in Advances in Therapy, disclosing his role as senior author upfront. The study pooled randomized controlled trials of the five FDA-approved adjunctive antipsychotics for major depressive disorder, drawing directly from the trials cited in each drug's product labeling. It excluded the olanzapine-fluoxetine combination, since that product carries a different, treatment-resistant depression indication. From the included trials, the team extracted outcomes like response and remission along with key safety measures. They then calculated effect sizes, such as odds ratios and point-change differences versus placebo, for each agent. Dr. Citrome introduces the 95% confidence interval as the range likely to contain a drug's true effect, noting there remains a 5% chance the true value falls outside it. Confidence intervals across the five drugs overlap substantially, so a head-to-head trial is still the only way to confirm real differences. Absent that, relative effect size offers only better or worse odds, which he compares to rolling dice. On efficacy, measured by MADRS score change and clinical global impression severity, lumateperone showed a larger effect size than quetiapine extended-release, aripiprazole, brexpiprazole, and cariprazine, with meaningful variation by dose. Safety findings differentiated the agents further. Using a threshold of at least 7% weight gain, lumateperone stood apart as not associated with weight gain or akathisia. It performed in the middle of the group for sedation, more sedating than cariprazine, brexpiprazole, and aripiprazole, but less than quetiapine extended-release. Dr. Citrome emphasizes that tolerability, more than efficacy, distinguishes these agents, and that tolerability drives adherence, which in turn drives outcomes and downstream costs for payers.

Up next, in "Second Meta-Analysis Reveals Differences Among MDD Add-On Therapies," Dr. Citrome examines how an independent analysis compares against his own team's findings.