FDA Approves Caplyta for Adjunctive Treatment of Major Depressive Disorder

The US Food and Drug Administration (FDA) has approved Johnson & Johnson’s lumateprone (Caplyta) as an adjunctive therapy for the treatment of adults with major depressive disorder (MDD).¹

“The FDA approval of Caplyta as an adjunctive treatment for patients with unipolar MDD not fully responding to antidepressant monotherapy is a significant addition to our current pharmacopeia. Caplyta, although categorized as an atypical antipsychotic, has consistently demonstrated a low incidence of adverse events that are commonly seen with atypical antipsychotics, including movement disorders, metabolic disturbances, weight gain, and prolactin elevation. Caplyta’s incidence of these adverse events has been similar to placebo in its clinical trials for the treatment of schizophrenia and bipolar depression, and now as an adjunctive treatment of unipolar MDD,” said John J. Miller, MD, Editor in Chief of Psychiatric Times.

The 2 phase 3 double-blind, placebo-controlled clinical trials submitted to the FDA, studies 501 and 502, both demonstrated a significantly superior improvement in the Montgomery-Asberg Depression Rating Scale (MADRS) at week 6 compared with placebo at the dose of 42 mg per day. Study 501, which included 485 patients, demonstrated a 4.9-point decrease in the MADRS score for patients on Caplyta vs to an oral antidepressant plus placebo who all continued on their primary prestudy antidepressant. Study 502, which included 480 patients, demonstrated a 4.5-point decrease in the MADRS score for patients on Caplyta vs placebo who all continued on their primary prestudy antidepressant. Treatment-emergent adverse events in study 501 that were greater than or equal to 5% and more than twice that seen in the placebo plus antidepressant group included dry mouth, fatigue, and tremor.

Long-term data from the 503 open-label extension safety study showed that Caplyta was safe and well tolerated, and had a safety profile consistent with those of Studies 501 and 502. Patients experienced low risk of weight gain, cardiometabolic effects, and extrapyramidal symptoms. Caplyta also demonstrated the potential to help patients achieve remission; during the 26-week safety study, 80% of patients responded to treatment and 65% of patients experienced remission (defined as MADRS Total score ≤ 10) at 6 months.²

“Depression is a complex disorder that affects each person differently, underscoring the urgent need for a range of effective and well-tolerated treatment options,” said Roger S. McIntyre, MD, FRCPC, professor of psychiatry and pharmacology at the University of Toronto. “For people who are still experiencing lingering depressive symptoms while on an antidepressant, adding Caplyta to a patient’s treatment regimen may offer early improvement, with the potential for remission—the ultimate goal of treatment.”¹

This approval is the first under Johnson & Johnson leadership following its acquisition of Intra-Cellular Therapies. It is also the fourth indication for Caplyta, which is the first and only FDA-approved treatment for bipolar I and II depression in adults, as an adjunctive and monotherapy; and an approved treatment for schizophrenia in adults.

“Caplyta has the potential to become a new standard of care across multiple mental health disorders, including major depressive disorder,” said Bill Martin, PhD, the global therapeutic area head of neuroscience at Johnson & Johnson Innovative Medicine. “This approval is a testament to our nearly 70-year commitment of bringing innovative and differentiated therapies that redefine treatment expectations—and introduce the possibility of remission—to patients living with some of today’s most prevalent and debilitating mental health conditions.”¹

Johnson & Johnson recently submitted to the FDA a supplemental New Drug Application for Caplyta with long-term data evaluating the safety and efficacy of the medication for the prevention of relapse in schizophrenia.³ Investigators are also studying Caplyta for the treatment of other neuropsychiatric and neurological disorders.

Dr Miller is on the speakers’ bureau of Intra-Cellular, the manufacturer of Caplyta.

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. November 6, 2025. Accessed November 6, 2025. 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. Earley W. Long-term adjunctive lumateperone treatment in major depressive disorder: results from a six-month open-label extension study. Poster presented at: American Psychiatric Association Annual Meeting; May 17-21, 2025.

3. Supplemental new drug application submitted to U.S. FDA for CAPLYTA® (lumateperone) with data demonstrating significant schizophrenia relapse prevention compared to placebo. News release. July 8, 2025. Accessed November 6, 2025. https://www.jnj.com/media-center/press-releases/supplemental-new-drug-application-submitted-to-u-s-fda-for-caplyta-lumateperone-with-data-demonstrating-significant-schizophrenia-relapse-prevention-compared-to-placebo