Adjunctive Lumateperone Maintains Remission Rates for Major Depressive Disorder

Lumateperone (Caplyta) in combination with an antidepressant showed significantly greater remission rates for adults with major depressive disorder (MDD) compared with the placebo and an antidepressant at 6 weeks. Investigators observed sustained benefits through 6 months in an open-label extension trial.¹

“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, professor of psychiatry and chief of the division of mood and anxiety disorders treatment and research program at the Perelman School of Medicine at the University of Pennsylvania, said in a news release.¹ “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. The findings demonstrate that adjunctive lumateperone may almost double the likelihood of remission, with benefits sustained over 6 months, offering renewed hope to millions of adults seeking recovery from this disease."

Recent FDA Approval of Lumateperone

In November 2025, the FDA approved lumateperone as an adjunct therapy in combination with antidepressants for the treatment of MDD, marking the fourth approval of the drug. Lumateperone is also approved for bipolar I and II as an adjunctive and monotherapy and for the treatment of schizophrenia.²

This approval was based on Study 501 (NCT04985942) and Study 502 (NCT05061706), phase 3 double-blind and placebo-controlled trials showing statistically significant and clinically meaningful improvements in depression symptoms compared with oral antidepressants. Both studies included a 2-week screening period prior to the study, a 6-week treatment period, and a 1-week safety follow-up period. Treatment included the placebo or lumateperone 42 mg daily, with the primary outcome being the change from baseline to day 43 in the Montgomery-Åsberg Depression Rating Scale. The secondary outcome included change from baseline to day 43 in the Clinical Global Impression Scale-Severity.^3,4

Results of the Studies

At 6 weeks, approximately 25.5% of patients receiving lumateperone achieved remission at 6 weeks compared with 13.6% receiving the placebo. Approximately 10.6% of patients achieved complete remission compared with 5.6%, respectively. Greater remission rates were also seen with lumateperone compared with the placebo across patient subgroups, including age, antidepressant type, and baseline severity.¹

The company also announced results for Study 503 (NCT05061719), which was a multicenter, open-label extension trial that lasted 26 weeks. Patients from Study 501 and 502 were able to be included where they received the open-label drug and continued their background antidepressant from the lead-in study.⁵

Efficacy was maintained with the drug, showing that approximately 65.4% of patients reached remission. Additionally, complete remission was reached by approximately 44.1% of patients. By the end of treatment, 42.8% of patients had maintained remission, and the rates increased over the study. Further, the remission rates were consistent across patient subgroups, such as age, antidepressant type, and baseline severity.¹

The full data was presented at the 64th Annual Meeting of the American College of Neuropsychopharmacology, which was held from January 12 to 15 in Nassau, Bahamas.¹

“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, global therapeutic area head of neuroscience at Johnson & Johnson Innovative Medicine, said in the news release.¹ “Too many patients spend years cycling through treatments, settling for ‘good enough’ because they don’t realize complete relief is possible. These data demonstrate that remission is within reach and should be the expectation, not the exception.”

READ MORE: Mental and Behavioral Health Resource Center

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REFERENCES

1. New clinical data highlights Caplyta (lumateperone) as a promising option for achieving remission in adults with major depressive disorder. News release. Johnson and Johnson. January 16, 2026. Accessed January 19, 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. Gallagher A. FDA approves lumateperone as adjunct therapy for major depressive disorder. November 6, 2025. Accessed January 19, 2026. https://www.drugtopics.com/view/fda-approves-lumateperone-as-adjunct-therapy-for-major-depressive-disorder

3. Multicenter study of lumateperone as adjunctive therapy in the treatment of patients with major depressive disorder. ClinicalTrials.gov identification: NCT05061706. Updated May 9, 2025. Accessed January 19, 2026. https://clinicaltrials.gov/study/NCT05061706

4. Clinical trial of lumateperone as adjunctive therapy in the treatment of patients with major depressive disorder. ClinicalTrials.gov identification: NCT04985942. Updated May 2, 2025. Accessed January 19, 2026. https://www.clinicaltrials.gov/study/NCT04985942

5. An open-label study of lumateperone as adjunctive therapy in the treatment of patients with major depressive disorder. ClinicalTrials.gov identification: NCT05061719. Updated November 3, 2025. Accessed January 19, 2026. https://www.clinicaltrials.gov/study/NCT05061719