Second Meta-Analysis Reveals Differences Among MDD Add-On Therapies

"Second Meta-Analysis Reveals Differences Among MDD Add-On Therapies " takes up an independently run analysis that puts the first study's findings to the test.

Turning to a second, independently conducted network meta-analysis published this year in JAMA Psychiatry, Dr. Citrome highlights how it differs methodologically from the study discussed previously. Rather than relying only on trials cited in product labeling, the McIntyre and colleagues analysis included all available randomized controlled trials of the five adjunctive antipsychotics. It was also conducted without manufacturer involvement. Both analyses assessed efficacy using change on the Montgomery-Asberg Depression Rating Scale, and Dr. Citrome notes the efficacy findings were largely consistent between the two, which he views as useful cross-validation of the earlier results. Where the studies diverge is acceptability. The McIntyre analysis measured discontinuation for any reason as a proxy for how well patients tolerated staying on treatment. Under that measure, lumateperone showed comparatively lower acceptability than in the manufacturer-sponsored analysis. Dr. Citrome cautions against over-interpreting that discontinuation figure, since clinical trial populations differ meaningfully from real-world patients. Trial participants may leave a study for reasons unrelated to the drug itself, and trials offer incentives to remain enrolled that don't exist for patients simply taking a medicine day to day. Real-world patients also tend to carry more comorbidities, including substance use, than the more selected populations typically enrolled in registrational trials. Dr. Citrome treats the discontinuation data as a rough signal rather than a precise prediction, and stresses that he counsels patients up front on what to expect from any adjunctive antipsychotic. He closes by underscoring that evidence-based medicine means combining trial data with clinical judgment and the patient's own values and preferences. Patients who feel ownership over their treatment choice are considerably more likely to stay adherent.

In "Formulary Strategy and the Evidence Gaps Still Facing MDD Add-On Therapy," the series closes with Dr. Citrome's view on formulary strategy and the evidence still needed.