New Lumateperone Data Highlight Need for Earlier Treatment Adjustment in MDD

New data presented at the 2026 Neuroscience Education Institute Spring Congress may help clinicians weigh adjunctive treatment options for adults with major depressive disorder (MDD) who do not achieve adequate symptom control with antidepressant therapy alone.

Lumateperone (Caplyta; Johnson & Johnson) was approved by the US FDA on November 6, 2025, as an adjunctive therapy with antidepressants for adults with MDD.¹ In a new network meta-analysis of 10 randomized clinical trials, lumateperone was favored across 4 efficacy measures among FDA-approved atypical antipsychotics used as adjunctive MDD therapies, including change from baseline in Montgomery-Åsberg Depression Rating Scale score, response, remission, and change from baseline in Clinical Global Impression-Severity score. The analysis also found no statistically significant weight gain with lumateperone compared with placebo plus antidepressant therapy, although somnolence risk was higher than placebo plus antidepressant therapy.²

In this interview, Leslie Citrome, MD, MPH, clinical professor of psychiatry and behavioral sciences at New York Medical College, discusses what the findings may mean for clinicians managing patients with persistent depressive symptoms. Citrome emphasizes the importance of reassessing treatment earlier when patients are not responding adequately to SSRI, SNRI, NDRI, or combination therapy, and highlights the need to match adjunctive treatment choices to each patient’s efficacy goals and tolerability concerns.

Editor’s note: Relevant disclosures for Citrome include H. Lundbeck A S, Axsome Therapeutics, Alkermes, Otsuka America Pharmaceutical, E.R. Squibb & Sons, Neurocrine Biosciences, Teva Pharmaceutical, and more.

References:

1. FDA approval of CAPLYTA® (lumateperone) has the potential to reset treatment expectations, offering hope for remission in adults with major depressive disorder. News release. Johnson & Johnson. November 6, 2025. Accessed May 12, 2026. https://www.jnj.com/media-center/press-releases/fda-approval-of-caplyta-lumateperone-has-the-potential-to-reset-treatment-expectations-offering-hope-for-remission-in-adults-with-major-depressive-disorder
2. Cutler AJ, Lemyre A, Zhang Q, et al. Efficacy and Safety of Lumateperone versus Atypical Antipsychotics as Adjunctive Therapy in Major Depressive Disorder: A Pooled-Dose Network Meta-Analysis. 2026 Neuroscience Education Institute (NEI) Spring Congress; May 1-3, 2026; Kissimmee, FL