SUMMARY

• Earley et al (2025)¹ presented a phase 3, 26-week, open-label extension (OLE) study that evaluated the long-term safety and antidepressant effects of CAPLYTA 42 mg adjunctive to antidepressant therapy (ADT) in adult patients with major depressive disorder (MDD) who had completed a phase 3, 6-week, double-blind, placebo-controlled study (study 501 or 502).
  • The mean±standard deviation (SD) change from baseline to the end of treatment in the CAPLYTA 42 mg+ADT group was -8.2±32.30 mg/dL for total cholesterol, -0.2±84.26 mg/dL for triglycerides, 1.1±15.56 mg/dL for glucose, -0.41±22.41 μIU/L for insulin, and -0.16±3.72 kg for weight.
• Tohen et al (2025)² conducted a 6-month OLE of a phase 3, 6-week, double-blind, placebo-controlled study assessing the long-term safety of CAPLYTA 42 mg in patients with major depressive episodes (MDEs) associated with bipolar I or bipolar II disorder.
  • The mean (standard error [SE]) change from baseline to day 175 was -2.5 (2.12) mg/dL for total cholesterol, 2.3 (4.49) mg/dL for triglycerides, 2.4 (1.45) mg/dL for glucose, and 0.1 (2.29) mIU/L for insulin, while the mean (SE) change in weight from baseline to day 175 was 0.0 (0.28) kg.
• Satlin et al (2020)³ presented results from a phase 3, open-label study that assessed the changes in weight and metabolic profile in patients with stable schizophrenia who switched from standard of care (SOC) treatment to CAPLYTA 42 mg for up to 1 year.
  • The mean change from SOC baseline to 1 year was -11.4 mg/dL for total cholesterol (P<0.001) and -2.1 kg for weight (P<0.001).

PRODUCT LABELING

Metabolic Changes

Antipsychotic drugs have caused metabolic changes, including hyperglycemia, diabetes mellitus, dyslipidemia, and weight gain.⁴ 

Hyperglycemia and Diabetes Mellitus

Hyperglycemia, in some cases extreme and associated with ketoacidosis, hyperosmolar coma, or death, has been reported in patients treated with antipsychotics. There have been reports of hyperglycemia in patients treated with CAPLYTA. Assess fasting plasma glucose before or soon after the initiation of CAPLYTA and monitor periodically during long-term treatment.⁴

Dyslipidemia

Antipsychotics have caused adverse alterations in lipids. Before or soon after the initiation of antipsychotic medications, obtain a fasting lipid profile at baseline and monitor periodically during treatment.⁴

Weight Gain

Weight gain has been observed with use of antipsychotics. Monitor weight at baseline and frequently thereafter.⁴

CLINICAL DATA

MDD, Adjunctive Therapy to Antidepressants

Earley et al (2025)¹ presented a phase 3, 26-week, OLE study that evaluated the long-term safety and antidepressant effects of CAPLYTA 42 mg adjunctive to ADT in adult patients with MDD who had completed a phase 3, 6-week, double-blind, placebo-controlled study (study 501 or 502).

• Patients (N=809) were administered CAPLYTA 42 mg once daily in the evening for 26 weeks.
• Potentially clinically significant (PCS) weight increase (≥7% increase in weight from baseline) was reported in 66/779 patients (8.5%), while PCS weight decrease (≥7% decrease in weight from baseline) was reported in 75/779 patients (9.6%). The incidence of PCS weight increase or decrease was low and similar.
• A summary of changes in body morphology, cardiometabolic parameters, and prolactin levels is presented in Table: Mean Change in Body Morphology, Cardiometabolic Parameters, and Prolactin.

Bipolar Disorder

Tohen et al (2025)² presented results from a 6-month OLE of a phase 3, 6-week, double-blind, placebo-controlled study assessing the long-term safety of CAPLYTA 42 mg in patients with MDEs associated with bipolar I or bipolar II disorder.

• Patients had completed the double-blind, randomized, placebo-controlled period of study 401, which consisted of 6 weeks of lumateperone 28 mg, CAPLYTA 42 mg, or placebo.
• Eligible patients (N=127) received CAPLYTA 42 mg/day for up to 175 days. The mean±SD CAPLYTA exposure was 127±64.4 days.
• PCS weight increase (≥7% increase in weight from baseline) was reported in 6/124 patients (4.8%), while PCS weight decrease (≥7% decrease in weight from baseline) was reported in 7/124 patients (5.6%).
• A summary of changes in body morphology and metabolic parameters is presented in Table: Changes in Body Morphology and Metabolic Parameters.

Schizophrenia

Satlin et al (2020)³ presented results from a phase 3, open-label study that assessed the changes in weight and metabolic profile in patients with stable schizophrenia who switched from SOC treatment to CAPLYTA 42 mg for up to 1 year.

• In this study, 602 patients received at least 1 dose of CAPLYTA.
• Overall, 1 year of treatment was completed by 239 patients.
• Assessments of weight change and metabolic parameters were performed for all patients who completed 1 year of treatment and patients classified at baseline as overweight (body mass index [BMI] 25-30 kg/m²) or obese (BMI ≥30 kg/m²).
  • Overall, 19% of the patient population reported PCS (≥7% change from baseline) weight decrease. PCS weight decrease from baseline was reported by 21% of overweight and 19% of obese patients.
  • PCS weight increase was reported by 5% of all patients, 3% of overweight patients, and 4% of obese patients.
  • Overall, 21% of patients shifted from obese to overweight BMI and 28% of patients shifted from overweight to normal BMI, while 4% of patients shifted from overweight to obese BMI.
• A summary of changes in body morphology and metabolic parameters is presented in Table: Changes in Body Morphology and Metabolic Parameters.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 06 October 2025.