The US FDA has approved lumateperone (Caplyta, Johnson & Johnson) for use as adjunctive therapy with antidepressants for the treatment of adults with major depressive disorder (MDD).

The oral atypical antipsychotic (dosage, 42 mg/d) is already approved in the US to treat adults with schizophrenia and bipolar I and II depression as monotherapy or added to lithium or valproate.

The approval of lumateperone added to antidepressant therapy in MDD was based on positive results from two phase 3, global, double-blind, placebo-controlled trials (Study 501 and Study 502).

Both studies met their primary and key secondary endpoints, providing statistically significant and clinically meaningful improvement in depression symptoms compared to an oral antidepressant plus placebo, as measured by Montgomery-Åsberg Depression Rating Scale (MADRS) and Clinical Global Impression Scale-Severity index (CGI-S) total scores.

At 6 weeks, a large separation in total MADRS score was observed between lumateperone and placebo in Study 501 (-4.9 points; effect size, 0.61) and Study 502 (-4.5 points; effect size, 0.56), the company noted in a press release.

Significant reductions in the key secondary endpoint of mean change in total CGI-S scores from baseline were also observed at 6 weeks in Study 501 (-0.7 points; effect size, 0.67) and Study 502 (-0.5 points, effect size 0.51).

“Depression is a complex disorder that affects each person differently, underscoring the urgent need for a range of effective and well-tolerated treatment options,” Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Ontario, Canada, said in the news release. 

“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,” said McIntyre.

The safety profile of lumateperone in MDD was consistent with the existing body of clinical data in its schizophrenia and bipolar depression I and II indications, the company said.

Lumateperone is contraindicated in elderly patients with dementia-related psychosis. Full prescribing information is available online.