Johnson and Johnson announced FDA’s approval of Caplyta in combination with oral antidepressants for the treatment of major depressive disorder (MDD) in adults.¹ This approval marks Caplyta’s fourth approved indication, the first and only FDA-approved treatment for bipolar I and II depression in adults, as an adjunctive and monotherapy, and is also approved for the treatment of schizophrenia in adults.¹

"Caplyta has the potential to become a new standard of care across multiple mental health disorders, including major depressive disorder," said Bill Martin, Ph.D., Global Therapeutic Area Head, Neuroscience, 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."

Why did FDA approve Caplyta?

Caplyta’s approval is based on positive results collected from two Phase III, global, double-blind, placebo-controlled trials Study 501 and 502, where both studies reached their primary and key secondary endpoints. They also provided statistically significant and clinically meaningful improvements in depression symptoms compared to an oral antidepressant plus placebo, as measured by the Montgomery-Asberg Depression Rating Scale (MADRS) and Clinical Global Impression Scale-Severity index (CGI-S) scores.¹ In Study 501 a significant separation in total MADRS score was seen between Caplyta and placebo, along with similar results in Study 502 at six weeks.¹ According to a news release from Johnson and Johnson, separation from placebo was seen as early as one week in Study 501 and two weeks in Study 502, along with significant reductions in key secondary endpoint of mean changes in total CGI-S scores from baseline in Study 501 at six weeks.

Caplyta’s safety profile remained consistent with the existing body of clinical data in its schizophrenia and bipolar depression I and II indications, with no new safety concerns being identified. The most common side effects of Caplyta include sleepiness, dizziness, nausea, dry mouth, feeling tired, and diarrhea.¹

Why did Johnson and Johnson focus on developing a MDD indication of Caplyta?

With MDD or clinical depression being one of the most common psychiatric disorders affecting an estimated 22 million American adults, oral antidepressants may only offer relief for a select few patients. 2 in 3 people living with MDD continue to experience residual symptoms despite treatment, significantly impacting overall quality of life.¹ According to a press release from Johnson and Johnson, MDD holds a significant economic burden, while also being the leading cause of disability in the U.S.

"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, M.D., FRCPC, professor of psychiatry and pharmacology, 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."

Sources

1. FDA approval of CAPLYTA® (lumateperone) has the potential to reset treatment expectations, offering hope for remission in adults with major depressive disorder Johnson and Johnson November 6, 2025 https://www.prnewswire.com/news-releases/fda-approval-of-caplyta-lumateperone-has-the-potential-to-reset-treatment-expectations-offering-hope-for-remission-in-adults-with-major-depressive-disorder-302606717.html