Adjunctive Lumateperone Nearly Doubles Remission Rates at 6 Weeks in Adults With Major Depressive Disorder

Johnson & Johnson has reported new phase 3 data showing that lumateperone (CAPLYTA^®), used adjunctively with an antidepressant, was associated with significantly higher remission rates in adults with major depressive disorder (MDD) compared with placebo plus an antidepressant at 6 weeks, with benefits maintained through 6 months in an open-label extension study. The findings were presented at the 64th Annual Meeting of the American College of Neuropsychopharmacology, held January 12–15 in Nassau, Bahamas.¹

The analysis evaluated data from 3 phase 3 studies of lumateperone, including pooled results from 2 pivotal randomized, placebo-controlled efficacy and safety trials (Studies 501 and 502) and a 6-month open-label extension safety study (Study 503). Remission outcomes were assessed using 3 definitions based on the Montgomery–Åsberg Depression Rating Scale (MADRS): remission (≤10), complete remission (≤5), and sustained remission (≤10 at each assessment). Across all measures, investigators observed clinically meaningful remission rates, supporting both the depth and durability of symptom improvement in adults with MDD.

“Today, remission is out of reach for the majority of patients with depression, which means they continue to struggle with persistent symptoms that negatively impact their daily lives,” Michael E. Thase, MD, said in a press release. “These data capture not only symptom reduction, but also the durability and depth of treatment response, which are critical benchmarks for patients and clinicians striving for lasting relief.”

In pooled data from the pivotal trials, 25.5% of participants receiving adjunctive lumateperone achieved remission at 6 weeks compared with 13.6% of those receiving placebo (nominal P < .001). Complete remission was achieved by 10.6% of participants treated with lumateperone versus 5.6% in the placebo group (P < .01). Higher remission rates with lumateperone were consistent across patient subgroups, including age, baseline depression severity, and antidepressant class (selective serotonin reuptake inhibitor or serotonin-norepinephrine reuptake inhibitor).

In study 503, a 6-month open-label extension involving 809 participants, remission rates increased with continued treatment. By the end of the study, 65.4% of participants had achieved remission, and 44.1% reached complete remission. Sustained remission was observed in 42.8% of participants, with rates rising over time from 28.6% at week 8 to 40.8% at week 24. Remission outcomes remained consistent across prespecified patient subgroups.

“What matters most to patients isn’t just an improvement in symptoms, but sustained relief that allows them to truly reclaim their lives,” Bill Martin, PhD, said in the company statement.

Lumateperone was approved by the US Food and Drug Administration in November 2025 as an adjunctive therapy for MDD and is also indicated for the treatment of schizophrenia and depressive episodes associated with bipolar I or II disorder.² The drug’s mechanism of action is unknown; however, it is characterized by high serotonin 5-HT₂A receptor occupancy and moderate dopamine D₂ receptor occupancy at therapeutic doses. The recommended dose is 42 mg, and dose titration is not required.

In July 2025, a supplemental new drug application was submitted to the FDA seeking approval of lumateperone for relapse prevention in schizophrenia, based on results from a phase 3, double-blind, multicenter, placebo-controlled randomized withdrawal trial.³

1. Johnson & Johnson. New clinical data highlights CAPLYTA® (lumateperone) as a promising option for achieving remission in adults with major depressive disorder. News release. January 16, 2026. Accessed January 16, 2026. https://www.jnj.com/media-center/press-releases/new-clinical-data-highlights-caplyta-lumateperone-as-a-promising-option-for-achieving-remission-in-adults-with-major-depressive-disorder
2. Halsey G. Lumateperone Gets FDA Nod as Adjunctive Therapy for Major Depressive Disorder. Patient Care Online. November 6, 2025. https://www.patientcareonline.com/view/lumateperone-gets-fda-not-as-adjunctive-therapy-for-major-depressive-disorder
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