SUMMARY

• A phase 3, 6-week, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study assessed the efficacy and safety of CAPLYTA 42 mg adjunctive to antidepressant therapy (ADT) in patients with major depressive disorder (MDD) who had an inadequate response to ADT (study 501).¹
  • Mean changes (standard error [SE]) in lipid parameters from baseline to the end of treatment in the CAPLYTA 42 mg+ADT group were as follows: total cholesterol,
    -10.3 (2.08) mg/dL; low-density lipoprotein (LDL) cholesterol, -9.4 (1.91) mg/dL; high-density lipoprotein (HDL) cholesterol, -0.4 (0.77) mg/dL; and triglycerides,
    -4.7 (5.13) mg/dL.
• A phase 3, 6-week, randomized, double-blind, placebo-controlled, multicenter, international study evaluated the efficacy and safety of CAPLYTA 42 mg adjunctive to ADT in patients with MDD who had an inadequate response to ADT (study 502).²
  • Mean changes (standard deviation [SD]) in lipid parameters from baseline to the end of treatment in the CAPLYTA 42 mg+ADT group were as follows: total cholesterol,
    -9.3 (35.41) mg/dL; LDL cholesterol, -9.4 (31.76) mg/dL; HDL cholesterol,
    -0.9 (10.57) mg/dL; and triglycerides, -2.0 (97.27) mg/dL.
• A 26-week open-label extension (OLE) study evaluated the long-term safety and tolerability of CAPLYTA 42 mg as adjunctive therapy to ADT in adult patients with MDD who had completed study 501 or 502.³
  • Mean changes (SD) in lipid parameters from baseline to the end of treatment in the CAPLYTA 42 mg+ADT group were as follows: total cholesterol, -8.2 (32.30) mg/dL; LDL cholesterol, -9.6 (30.42) mg/dL; HDL cholesterol, 0.1 (11.79) mg/dL; and triglycerides, -0.2 (84.26) mg/dL.
• A 6-month OLE of a phase 3 study (study 401) that assessed the long-term safety and tolerability of CAPLYTA 42 mg in patients with major depressive episodes (MDEs) associated with bipolar I or bipolar II disorder found no notable changes in lipid parameters.⁴
  • Mean changes (SE) in lipid parameters from baseline to day 175 for the CAPLYTA 42 mg group were as follows: total cholesterol, -2.5 (2.12) mg/dL; LDL cholesterol, -5.8 (1.90) mg/dL; HDL cholesterol, 1.4 (0.82) mg/dL; and triglycerides, 2.3 (4.49) mg/dL.
• A 6-week, phase 3, randomized, double-blind, placebo-controlled, multicenter study that evaluated the efficacy and safety of CAPLYTA 28 or 42 mg as adjunctive treatment to lithium or valproate in patients with MDEs associated with bipolar I or bipolar II disorder (study 402) found that changes in lipid parameters were minimal.⁵
  • Mean changes (SD) in lipid parameters from baseline to the end of treatment in the CAPLYTA 42 mg group were as follows: total cholesterol, -6.5 (32.2) mg/dL; LDL cholesterol, -5.9 (27.0) mg/dL; HDL cholesterol, -0.6 (11.9) mg/dL; and triglycerides, -1.6 (57.9) mg/dL.
• A pooled analysis of two phase 3, randomized, double-blind, placebo-controlled, 6-week trials (ie, studies 401 and 404) assessed the metabolic profile of CAPLYTA 42 mg monotherapy in the treatment of patients with bipolar depression. Mean changes from baseline in lipid parameters were similar between the treatment groups.⁶
  • Mean changes in lipid parameters from baseline to the last on-treatment measurement in the CAPLYTA 42 mg group were as follows: total cholesterol,
    -0.6 mg/dL; LDL cholesterol, -0.7 mg/dL; HDL cholesterol, 0.4 mg/dL; and triglycerides, -1.4 mg/dL.
• A 6-week, open-label, outpatient, antipsychotic switch study evaluated the efficacy and safety of CAPLYTA 42 mg in patients with stable schizophrenia (study 303).⁷
  • Significant decreases from previous antipsychotics baseline were observed after week 1 of CAPLYTA treatment in total cholesterol (unadjusted P<0.001) and LDL cholesterol (unadjusted P<0.01), which were sustained for the rest of the treatment period.
• A phase 3, randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of CAPLYTA in patients with schizophrenia (study 301).⁸
  • There were no significant mean changes in cholesterol or triglycerides from baseline to day 28 compared with placebo.
• A phase 2, randomized, double-blind, placebo- and active-controlled, multicenter clinical trial evaluated the efficacy and safety of CAPLYTA in patients with schizophrenia (study 005).⁹
  • In post hoc comparisons to risperidone, CAPLYTA 42 mg and 84 mg treatment resulted in statistically significantly lower total cholesterol (CAPLYTA 42 mg, P=0.012; CAPLYTA 84 mg, P=0.004) and triglycerides (CAPLYTA 42 mg, P=0.074; CAPLYTA 84 mg, P=0.002).
• A pooled analysis of 3 randomized, double-blind, placebo-controlled trials (ie, studies 005, 301, and 302) assessed the safety and tolerability of CAPLYTA 42 mg in the treatment of schizophrenia.¹⁰
  • Triglycerides decreased in patients receiving CAPLYTA but increased in those receiving placebo. Additionally, CAPLYTA treatment led to similar mean changes in total cholesterol and LDL cholesterol levels as placebo.

PRODUCT LABELING

Metabolic Changes

Antipsychotic drugs have been reported to have caused metabolic changes, including hyperglycemia, diabetes mellitus, dyslipidemia, and weight gain.¹¹

Dyslipidemia

Antipsychotics have been reported to have caused adverse alterations in lipids. Before or soon after initiation of antipsychotic medications, obtain a fasting lipid profile at baseline and monitor periodically during treatment.¹¹

CLINICAL DATA

MDD, Adjunctive Therapy to Antidepressants

Durgam et al (2025)¹ conducted a phase 3, 6-week, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study to assess the efficacy and safety of CAPLYTA 42 mg adjunctive to ADT in patients with MDD who had an inadequate response to ADT (study 501).

• Patients were randomized (1:1) to receive either CAPLYTA 42 mg (n=242) or placebo (n=243) as adjunctive treatment to ADT for 6 weeks; this was followed by a 1-week safety follow-up period.
• Changes in lipid parameters at end of treatment were not clinically significant and were generally similar between the treatment groups; see Table: Changes in Lipid Parameters at End of Treatment.

A phase 3, 6-week, randomized, double-blind, placebo-controlled, multicenter, international study evaluated the efficacy and safety of CAPLYTA 42 mg adjunctive to ADT in patients with MDD who had an inadequate response to ADT (study 502).²

• Patients were randomized (1:1) to receive either CAPLYTA 42 mg (n=242) or placebo (n=238) as adjunctive treatment to ADT for 6 weeks; this was followed by a 1-week safety follow-up period.
• Changes in lipid parameters at end of treatment were not clinically relevant and were generally similar between the treatment groups; see Table: Changes in Lipid Parameters at End of Treatment.

Earley et al (2025)³ presented a 26-week OLE study that evaluated the long-term safety and tolerability of CAPLYTA 42 mg as adjunctive therapy to ADT in adult patients with MDD who had completed study 501 or 502.

• Patients (N=809) were administered CAPLYTA 42 mg once daily in the evening for 26 weeks.
• Changes in lipid parameters at end of treatment were minimal; see Table: Changes in Lipid Parameters.

Bipolar Depression

Tohen et al (2025)⁴ presented results from a 6-month OLE of a phase 3 study (study 401) assessing the long-term safety and tolerability of CAPLYTA 42 mg in patients with MDEs associated with bipolar I or bipolar II disorder.

• Eligible patients (N=127) received CAPLYTA 42 mg/day for 175 days.
• No notable changes were reported in lipid parameters, including total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides; see Table: Changes in Lipid Parameters.

Suppes et al (2023)⁵ conducted a phase 3, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of CAPLYTA as adjunctive treatment to lithium or valproate in patients with MDEs associated with bipolar I or bipolar II disorder (study 402).

• Patients were randomized (1:1:1) to receive CAPLYTA 28 mg (n=176), CAPLYTA 42 mg (n=177), or placebo (n=176) for 6 weeks; this was followed by a 2-week safety follow-up period.
• No notable changes were reported at end of treatment in lipid parameters, including total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides; see Table: Changes in Lipid Parameters at End of Treatment.

Davis et al (2021)⁶ presented results of a pooled analysis of two phase 3, randomized, double-blind, placebo-controlled, 6-week trials (ie, studies 401 and 404) to assess the metabolic profile of CAPLYTA 42 mg monotherapy in the treatment of patients with bipolar depression.

• The combined safety population from the 2 studies comprised 746 patients (CAPLYTA, n=372; placebo, n=374).
• Mean changes from baseline to last on-treatment measure in lipid parameters were similar between the treatment groups; see Table: Changes in Lipid Parameters from Baseline to the Last On-treatment Measure.

Schizophrenia

Correll et al (2021)⁷  conducted a 6-week, open-label, outpatient, antipsychotic switch study to evaluate the efficacy and safety of CAPLYTA 42 mg in patients with stable schizophrenia (study 303).

• The safety population comprised 301 patients who had received at least 1 dose of CAPLYTA 42 mg.
• Significant decreases from previous antipsychotics baseline were observed after week 1 of CAPLYTA treatment in total cholesterol (unadjusted P<0.001) and LDL cholesterol (unadjusted P<0.01); these decreases were sustained for the rest of the treatment period.

Correll et al (2020)⁸  conducted a phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of CAPLYTA in patients with schizophrenia (study 301).

• Patients were randomized (1:1:1) to receive CAPLYTA 28 mg (n=150), CAPLYTA 42 mg (n=150), or placebo (n=149; n values are based on safety population) for 4 weeks. A follow-up safety assessment was performed approximately 2 weeks after the last dose of study medication.
• There were no significant mean changes in cholesterol and triglycerides from baseline to day 28 compared with placebo.

Lieberman et al (2016)⁹ conducted a phase 2, randomized, double-blind, placebo- and active-controlled, multicenter clinical trial to evaluate the efficacy and safety of CAPLYTA in patients with schizophrenia (study 005).

• Patients were randomized 1:1:1:1 to receive CAPLYTA 42 mg (n=84), CAPLYTA 84 mg (n=83), risperidone 4 mg (n=82), or placebo (n=85) for 4 weeks.
• In post hoc comparisons to risperidone, CAPLYTA 42 mg and 84 mg treatment resulted in statistically significantly lower total cholesterol (CAPLYTA 42 mg, P=0.012; CAPLYTA 84 mg, P=0.004) and triglycerides (CAPLYTA 42 mg, P=0.074; CAPLYTA 84 mg, P=0.002).

Kane et al (2021)¹⁰ performed a pooled analysis of 3 randomized, double-blind, placebo-controlled trials (ie, studies 005, 301, and 302) to assess the safety and tolerability of CAPLYTA 42 mg in the treatment of schizophrenia.

• The pooled population comprised 1073 patients with acute exacerbation of schizophrenia (CAPLYTA 42 mg [n=406], risperidone 4 mg [n=255], or placebo [n=412]).
• Patients were treated with CAPLYTA for 4 weeks in studies 005 and 301 and for 6 weeks in study 302. Additionally, studies 005 and 302 included risperidone 4 mg as an active control for assay sensitivity.
• Triglycerides decreased in patients receiving CAPLYTA but increased in those receiving placebo, whereas mean changes from baseline to the last on-treatment value in total cholesterol, HDL, and LDL cholesterol levels were similar between the CAPLYTA and placebo groups; see Table: Changes in Lipid Parameters from Baseline to the Last On-treatment Value.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 15 September 2025.