SUMMARY

• Durgam et al (2025)¹ conducted a 6-week, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of CAPLYTA 42 mg in patients with major depressive episodes (MDEs) associated with major depressive disorder (MDD) or bipolar depression with mixed features.
  • CAPLYTA showed improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline to day 43 compared with placebo.
    • In the combined MDD with mixed features and bipolar depression with mixed features group, the least squares (LS) mean change from baseline for CAPLYTA 42 mg was -18.1 vs -12.4 for placebo, with LS mean difference of -5.7 (95% confidence interval [CI]: -7.60 to -3.84; effect size [ES]=-0.64; P<0.0001).^1,2
  • CAPLYTA also showed improvement in the Clinical Global Impression-Severity (CGI-S) score from baseline to day 43 compared with placebo.
    • In the combined MDD with mixed features and bipolar depression with mixed features group, the LS mean change from baseline for CAPLYTA 42 mg was -1.8 vs -1.2 for placebo, with LS mean difference of -0.6 (95% CI: -0.81 to -0.39; ES=-0.59; P<0.0001).^1,2
  • In the combined MDD and bipolar depression population, the treatment-emergent adverse event (TEAE) rate was 54.2% for CAPLYTA vs 37.3% for placebo. Specifically, among patients with MDD, the TEAE rate was 51.1% for CAPLYTA vs 32.3% for placebo; in patients with bipolar depression, the TEAE rate was 57.0% for CAPLYTA vs 42.0% for placebo.¹

PRODUCT LABELING

CAPLYTA is an atypical antipsychotic indicated for: treatment of schizophrenia in adults; treatment of depressive episodes associated with bipolar I or II disorder (bipolar depression) in adults, as monotherapy and as adjunctive therapy with lithium or valproate; and adjunctive therapy with antidepressants for the treatment of major depressive disorder (MDD) in adults.³

CLINICAL DATA

Durgam et al (2025)¹ conducted a randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of CAPLYTA in patients with MDEs associated with MDD or bipolar depression with mixed features.

• Key inclusion criteria were:
  • Meeting the Diagnostic and Statistical Manual of Mental Disorders, 5^th Edition (DSM-5) criteria for mixed features
  • A Young Mania Rating Scale (YMRS) total score between 4 and 16
  • A MADRS total score ≥24
  • A CGI-S score ≥4
• Patients were randomly assigned (1:1) to receive either CAPLYTA 42 mg (n=193) or placebo (n=195) for 6 weeks; this was followed by a 2-week safety follow-up period.
• The primary efficacy endpoint was the change in MADRS total score from baseline to day 43, and the key secondary efficacy endpoint was the change in CGI-S score from baseline to day 43.
• During the study, CAPLYTA showed improvement in both MADRS total score and CGI-S score from baseline to day 43 vs placebo; see Table: Change in MADRS Total Score and CGI-S Score at Day 43 (Modified Intent-to-Treat Population).

• In the combined MDD and bipolar depression population, the TEAE rate was 54.2% for CAPLYTA vs 37.3% for placebo. Specifically, among patients with MDD, the TEAE rate was 51.1% for CAPLYTA vs 32.3% for placebo; in patients with bipolar depression, the TEAE rate was 57.0% for CAPLYTA vs 42.0% for placebo.¹
• In the combined MDD and bipolar depression population, discontinuous rate due to AE was 4.7% for CAPLYTA vs 1.6% for placebo. Specifically, among patients with MDD, the discontinuous rate was 2.2% for CAPLYTA vs 1.1% for placebo; in patients with bipolar depression, the discontinuous rate was 7.0% for CAPLYTA vs 2.0% for placebo.
• In the combined MDD and bipolar depression population, the most common TEAEs (occurring in ≥5% of the CAPLYTA group and more than twice that of placebo) were somnolence (CAPLYTA, 12.5%; placebo, 1.6%), dizziness (CAPLYTA, 12.0%; placebo, 2.1%), and nausea (CAPLYTA, 9.9%; placebo, 1.6%). Specifically, among patients with MDD, the most common TEAEs were somnolence (CAPLYTA, 12.0%; placebo, 1.1%), dizziness (CAPLYTA, 12.0%; placebo, 4.3%), and nausea (CAPLYTA, 10.9%; placebo, 1.1%); in patients with bipolar depression, the most common TEAEs were somnolence (CAPLYTA, 13.0%; placebo, 2.0%), dizziness (CAPLYTA, 12.0%; placebo, 0%), nausea (CAPLYTA, 9.0%; placebo, 2.0%), dry mouth (CAPLYTA, 5.0%; placebo, 2.0%), and fatigue (CAPLYTA, 5.0%; placebo, 1.0%).

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 10 October 2025.