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TOPLINE:

The use of 42 mg lumateperone combined with antidepressant therapy was linked to significantly reduced severity of depression and anxiety, as well as greater response and remission rates, and was generally well tolerated in adults with major depressive disorder (MDD) compared to placebo, a new phase 3 trial showed. The antipsychotic was approved by the US FDA previously for the treatment of schizophrenia and depressive episodes associated with bipolar I and II disorders.

METHODOLOGY:

• The phase 3, randomized, double-blind, placebo-controlled trial was conducted from 2021 to 2024 and included nearly 500 adults with MDD (mean age, 45 years; 66% women; 77% White, 10% Asian, 8% Black individuals) across 54 international sites.
• Patients were randomly assigned to receive either 42 mg lumateperone (n = 242) or placebo (n = 243) in addition to existing antidepressant therapy (citalopram or escitalopram).
• The primary outcome was change from baseline to day 43 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score.
• Other outcomes included changes from baseline to day 43 in Clinical Global Impression Scale-Severity (CGI-S) score, Quick Inventory of Depressive Symptomatology-Self Report 16-item (QIDS-SR-16) total score, and Generalized Anxiety Disorder seven-item (GAD-7) total score. Safety outcomes were also assessed.

TAKEAWAY:

• Lumateperone plus antidepressant therapy was associated with significantly greater reductions from baseline to day 43 in MADRS total score (least-squares mean difference [LSMD], -4.9; P < .0001) and CGI-S score (LSMD, -0.7; P < .0001) than placebo.
• The adjunctive lumateperone vs adjunctive placebo group also had significantly higher response rates (46% vs 24%, respectively; P < .0001) and higher remission rates (26% vs 14%; P < .001).
• Patient-reported depression symptoms, as measured by QIDS-SR-16 total score (LSMD, -2.4), and anxiety, as measured by GAD-7 total score (LSMD, -1.6) were associated with significant improvements for lumateperone compared with placebo (P < .0001 for both).
• The most common treatment-emergent adverse events for the lumateperone and placebo groups were dry mouth (11% and 2%, respectively), fatigue (10% and 2%, respectively), and tremors (5.0% and 0.4%, respectively).

IN PRACTICE:

“Lumateperone 42 mg adjunctive to ADT [antidepressant therapy] demonstrated significant, clinically meaningful efficacy over placebo adjunctive to ADT,” the investigators wrote.

The findings suggest that it is “a promising new treatment option for adults with MDD with inadequate ADT response,” they added.

SOURCE:

The study was led by Suresh Durgam, MD, Intra-Cellular Therapies, Bedminster, New Jersey. It was published online on August 25 in The Journal of Clinical Psychiatry.

LIMITATIONS:

Patients with treatment-resistant illness, imminent suicidal risk, or comorbid psychiatric illnesses other than MDD were excluded by the investigators, possibly limiting the generalizability of the findings. The study also had a short duration.

DISCLOSURES:

The study was funded by Intra-Cellular Therapies, a Johnson & Johnson company. Five investigators declared being full-time employees of Intra-Cellular Therapies and may have held equity in the company. Additional disclosures are fully listed in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.