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(lumateperone)

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CAPLYTA® (lumateperone)
Medical Information

CAPLYTA - Adverse Event - Suicide

Last Updated: 05/06/2026

SUMMARY

  • As noted in the product labelling, antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adults in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors. The safety and effectiveness of CAPLYTA have not been established in pediatric patients.1
  • In phase 2 and phase 3 studies, patients who were considered at risk for suicide were excluded from participation.2-12
  • In phase 2 and phase 3 clinical studies in patients with schizophrenia, suicidal ideation was reported in ≤1.4% and suicidal behavior was reported in ≤0.6% of patients treated with CAPLYTA 42 mg.2-4,13
  • In an open-label, multicenter study (Study 303) evaluating the long-term safety of CAPLYTA 42 mg in patients with schizophrenia:5
    • During the 1-year treatment period, suicidal ideation and behavior were reported in 9.6% and 0.3% of patients, respectively.
    • In the extended treatment period, 1.6% of patients reported suicidal ideation, with no cases of suicidal behavior.
  • An open-label study in patients with stable schizophrenia who were switched from standard-of-care antipsychotic therapy to CAPLYTA 42 mg found no cases of suicidal ideation or behavior during 6 weeks of CAPLYTA 42 mg treatment.14
  • In 3 clinical trials in patients with bipolar I or II disorder, suicidal ideation and emergence of suicidal ideation were reported in ≤10.3% and ≤8.9% of patients treated with CAPLYTA, respectively.6,7,9,15-18 In 1 clinical trial that evaluated patients with bipolar I or II disorder or major depressive disorder (MDD), suicidal ideation was reported in 6.3% of patients in the CAPLYTA 42 mg group.8
  • In a post hoc analysis of 3 pooled short term, phase 3 studies (Study 401, Study 402, Study 404) evaluating depression associated with bipolar II disorder, the emergence of suicidal ideation was reported in 4.1% of patients in the CAPLYTA 42 mg and no suicidal behavior was reported in patients with bipolar II disorder. 19
  • In 2 phase 3 clinical trials in patients with MDD, suicidal ideation and emergence of suicidal ideation were reported in ≤6.1% and ≤1.9% of patients treated with CAPLYTA 42 mg+ADT, respectively.10,11,20,21
  • In an open-label, multicenter study (Study 503) evaluating CAPLYTA 42 mg as adjunctive treatment to ADT in patients with MDD:12,22
    • Suicidal ideation was reported in 4.4% of patients during the 26-week treatment period, with 2.7% showing emergence of suicidal ideation and 0.1% showing worsening of suicidal ideation; no suicidal behavior was observed.

CLINICAL DATA

In phase 2 and phase 3 studies, patients who were considered at risk for suicide were excluded from participation. The Columbia Suicide Severity Rating Scale (C-SSRS) was used as a measurement of suicidal ideation and behavior as part of the overall safety analyses.2-12


Summary of Clinical Studies of CAPLYTA
Study Objective
Patients and Treatment Groups
Outcomes
Schizophrenia
A randomized, double‑blind, placebo‑controlled, phase 2 study (Study 005) evaluated the efficacy of CAPLYTA in patients with an acute exacerbation of schizophrenia.2 
  • Patients (N=335) were randomized to receive CAPLYTA 42 mg, lumateperone 84 mg, risperidone 2 mg (active control), or placebo for 4 weeks
  • During the treatment period, suicidal ideation was reported in 1 patient each in the lumateperone 84 mg, risperidone, and placebo groups.
  • No cases of suicidal ideation were reported in the CAPLYTA 42 mg group.
Correll et al (2020)13 conducted a randomized, double‑blind, placebo‑controlled, multicenter, phase 3 study (Study 301) that evaluated the efficacy and safety of CAPLYTA in patients with schizophrenia.3 
  • Patients were randomized (1:1:1) to receive lumateperone 28 mg (n=150), CAPLYTA 42 mg (n=150), or placebo (n=149) for 4 weeks. A safety follow-up occurred 2 weeks after the end of treatment period.
  • During the treatment period, suicidal ideation was reported in 1.4% of patients in each of the lumateperone 28 mg, CAPLYTA 42 mg, and placebo groups.
  • During the posttreatment period, suicidal ideation was reported in 0.7%, 1.4%, and 2.2% of patients in the lumateperone 28 mg, CAPLYTA 42 mg, and placebo groups, respectively.
  • No suicidal behavior was reported during the treatment or posttreatment periods.
A randomized, double‑blind, parallel‑group, placebo‑ and active-controlled, multicenter, phase 3 study (Study 302) evaluated the efficacy and safety of CAPLYTA in patients with schizophrenia.4 
  • Patients were randomized (1:1:1:1) to receive CAPLYTA 42 mg (n=174), lumateperone 14 mg (n=174), placebo (n=174), or risperidone 4 mg (n=174) for 6 weeks. A safety follow-up occurred 2 weeks after the end of treatment period.
  • During the treatment period, suicidal ideation was reported in 1.3%, 1.3%, and 2.3% of patients in the CAPLYTA 42 mg, risperidone, and placebo groups, respectively.
  • Suicidal behavior was reported in 0.6% of patients each in the lumateperone 14 mg and CAPLYTA 42 mg groups during the treatment period.
  • During the posttreatment period, suicidal ideation was reported in 0.6% of patients in the placebo group.
  • No suicidal behavior was reported during the posttreatment period.
An open-label, multicenter study (Study 303) evaluated the safety of CAPLYTA in patients with schizophrenia.5 
  • Patients received CAPLYTA 42 mg (n=602) for 1 year; this was followed by a 2‑week safety follow-up period and an extended treatment period.
  • During the 1-year treatment period:
    • Suicidal ideation and suicidal behavior were reported in 9.6% and 0.3% of patients, respectively.
    • TEAEs of suicidal ideation and suicidal attempt were reported in 1.3% and 0.2% of patients, respectively.
    • SAEs of suicidal ideation were reported in 2 patients.
  • During the safety follow-up of the 1-year treatment period:
    • Suicidal ideation and suicidal behavior were reported in 1.2% and 0.2% of patients, respectively.
  • During the extended treatment period:
    • Suicidal ideation and suicidal behavior were reported in 1.6% and 0% of patients, respectively.
    • There were no TEAEs related to suicidality.
Vanover et al (2017)14 conducted an open-label study to evaluate the safety and tolerability of CAPLYTA in patients with stable schizophrenia who were switched from standard‑of‑care antipsychotic therapy.
  • Patients (N=302) received CAPLYTA 42 mg for 6 weeks; this was followed by a switch to standard-of-care antipsychotic therapy and a reassessment approximately 2 weeks after the last dose.
  • No suicidal ideation or behavior was reported during CAPLYTA treatment.
Bipolar Depression
A randomized, double‑blind, placebo‑controlled, multicenter, phase 3 study (Part A, Study 401) and its OLE (Part B) evaluated the efficacy, safety, and tolerability of CAPLYTA in patients with MDEs associated with bipolar I or II disorder.6,15,16 
  • In Part A, patients were randomized to receive lumateperone 28 mg (n=183), CAPLYTA 42 mg (n=185), or placebo (n=186) for 6 weeks; this was followed by a 2‑week safety follow-up period.
  • In Part B, eligible patients received CAPLYTA 42 mg (n=127) for 6 months, followed by a 2‑week safety follow-up period.
  • Part A:
    • During the treatment period, emergence of suicidal ideation was reported in 8.9%, 4.9%, and 9.2% of patients in the lumateperone 28 mg, CAPLYTA 42 mg, and placebo groups, respectively.
    • During the posttreatment period, suicidal ideation was reported in 8.8%, 6.7%, and 4% of patients in the lumateperone 28 mg, CAPLYTA 42 mg, and placebo groups, respectively.
    • No suicidal behavior was reported in any groups during the treatment period; but was reported in 1 and 2 patients in the lumateperone 28 mg and CAPLYTA 42 mg groups, respectively, during the posttreatment period.
  • Part B:
    • During the open-label treatment period, suicidal ideation was reported in 10.3% of patients, and emergence of suicidal ideation was reported in 4% of patients.
    • During the posttreatment period, suicidal ideation was reported in 3.4% of patients.
    • No suicidal behavior was reported during the treatment and posttreatment periods.
Suppes et al (2023)17  conducted a randomized, double‑blind, placebo‑controlled, multicenter, phase 3 study (Study 402) that evaluated the efficacy and safety of CAPLYTA as adjunctive treatment to lithium or valproate in patients with MDEs associated with bipolar I or II disorder.7 
  • Patients were randomized to receive lumateperone 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.
  • During the treatment period, emergence of suicidal ideation was reported in 1.2%, 0.6%, and 4.1% of patients in the lumateperone 28 mg, CAPLYTA 42 mg, and placebo groups, respectively.
  • During the posttreatment period, suicidal ideation was reported in 1.8%, 2.4%, and 1.3% of patients in the lumateperone 28 mg, CAPLYTA 42 mg, and placebo groups, respectively.
  • No suicidal behavior was reported during the treatment and posttreatment periods.
A randomized, double‑blind, placebo‑controlled, multicenter, phase 3 study (Study 403) evaluated the efficacy and safety of CAPLYTA monotherapy in patients with MDEs associated with bipolar I or II disorder or MDD.8 
  • Patients were randomized to receive CAPLYTA 42 mg (n=243) or placebo (n=245) for 6 weeks; this was followed by a 2‑week safety follow-up period
  • During the treatment period, suicidal ideation was reported in 6.3% and 8% of patients in the CAPLYTA 42 mg and placebo groups, respectively.
  • No suicidal behavior was reported during the treatment period.
Calabrese et al (2021)9,18 conducted a phase 3, randomized, double-blind, placebo‑controlled study (Study 404) to evaluate the efficacy and safety of CAPLYTA for the treatment of MDEs associated with bipolar I or bipolar II disorder.
  • Patients were randomized (1:1) to receive CAPLYTA 42 mg (n=191) or placebo (n=190) for 6 weeks; this was followed by a 2-week safety follow-up period.
  • No suicidal behavior was reported in any group during the treatment period or in the posttreatment period.
  • The proportion of patients reporting suicidal ideation increased from 4.3% at baseline to 5.3% during the study period in the CAPLYTA 42 mg group and from 7.9% at baseline to 10.1% during the study period in the placebo group.
  • Suicidal ideation in the posttreatment period was reported in 1.1% and 5.5% of patients in the CAPLYTA 42 mg and placebo groups, respectively.
Durgam et al (2025)19  conducted a post hoc analysis that assessed the efficacy of CAPLYTA in 3 pooled short term, Phase 3 studies in patients with MDE associated with bipolar II disorder, who were treated with CAPLYTA monotherapy (Study 401, Study 404) or adjunctive therapy (Study 402).
  • All 3 studies included 6-week of CAPLYTA 42 mg monotherapy or adjunctive therapy period followed by 2 weeks of safety follow-up.
  • ITT population (CAPLYTA 42 mg, n=87 vs placebo, n=87)
  • During the treatment period, emergence of suicidal ideation was reported in 4.1% and 8% of patients in the CAPLYTA 42 mg and placebo groups, respectively.
  • No suicidal behavior was reported in any of the patients with bipolar II disorder.
MDD
Durgam et al (2025)10,20 conducted a phase 3, randomized, double-blind, placebo‑controlled, fixed‑dose study (Study 501) to assess the efficacy and safety of CAPLYTA adjunctive to ADT in patients with MDD who had an inadequate response to ADT.
  • 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.
  • No suicidal behavior was reported during the treatment and posttreatment periods.
  • Suicidal ideation was reported in 5.5% and 6.2% of patients in the CAPLYTA 42 mg+ADT and placebo+ADT groups, respectively, during the treatment period.
  • Emergence of suicidal ideation was reported in 1.4% and 3.5% of patients in the CAPLYTA 42 mg+ADT and placebo+ADT groups, respectively.
  • During the posttreatment period, suicidal ideation was reported in 4.3% and 0% of patients in the CAPLYTA 42 mg+ADT and placebo+ADT groups, respectively.
Durgam et al (2025)21 conducted a randomized, double‑blind, placebo‑controlled, multicenter, phase 3 study (Study 502) that evaluated the efficacy and safety of CAPLYTA as adjunctive treatment to ADT in patients with MDD.11
  • Patients were randomized 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.
  • During the treatment period, suicidal ideation was reported in 6.1% and 6.8% of patients in the CAPLYTA 42 mg+ADT and placebo+ADT groups, respectively.
  • Emergence of suicidal ideation was reported in 1.9% and 1.4% of patients in the CAPLYTA 42 mg+ADT and placebo+ADT groups, respectively, during the treatment period.
  • During the posttreatment period, suicidal ideation was reported in 2.1% and 13.3% of patients in the CAPLYTA 42 mg+ADT and placebo+ADT groups, respectively.
  • No suicidal behavior was reported during the treatment and posttreatment periods.
Durgam et al (2026)22 , conducted an open-label, multicenter study (Study 503) to evaluate the safety and tolerability of CAPLYTA as adjunctive treatment to ADT in patients with MDD.12
  • Patients received CAPLYTA 42 mg (n=809) as adjunctive treatment to ADT for 26 weeks; this was followed by a 2-week safety follow-up period.
  • Patients were excluded if they had a significant risk of suicidal behavior
  • There was no emergence of suicidal behavior during the open-label treatment; however, the emergence of suicidal ideation was reported in 2.7% of patients.
  • There was no emergence of serious suicidal ideation among patients.
  • Mild TEAEs of suicidal ideation were observed in 3 patients; 2 of which were considered unrelated to the study drug.
Abbreviations: ADT, antidepressant therapy; ITT, intent-to-treat; LS, least squares; MDD, major depressive disorder; MDE, major depressive episode; mITT, modified intent-to-treat; TEAE, treatment-emergent adverse event.

Literature Search

A literature search of MEDLINE®, EMBASE®, BIOSIS Previews®, and DERWENT® (and/or other resources, including internal/external databases) was conducted on 11 February 2026.

References

Show
1 CAPLYTA (lumateperone) [Prescribing Information]. Titusville, NJ: Intra-Cellular Therapies, Inc; https://www.intracellulartherapies.com/docs/caplyta_pi.pdf
2 Data on File. CAPLYTA. Clinical Study Report of Study 005. Intra-Cellular Therapies, Inc; 2015.  
3 Data on File. CAPLYTA. Clinical Study Report of Study 301. Intra-Cellular Therapies, Inc; 2016.  
4 Data on File. CAPLYTA. Clinical Study Report of Study 302. Intra-Cellular Therapies, Inc; 2017.  
5 Data on File. CAPLYTA. Clinical Study Report of Study 303. Intra-Cellular Therapies, Inc; 2025.  
6 Data on File. CAPLYTA. Clinical Study Report of Study 401. Intra-Cellular Therapies, Inc; 2021.  
7 Data on File. CAPLYTA. Clinical Study Report of Study 402. Intra-Cellular Therapies, Inc; 2021.  
8 Data on File. CAPLYTA. Clinical Study Report of Study 403. Intra-Cellular Therapies, Inc; 2023.  
9 Data on File. CAPLYTA. Clinical Study Report of Study 404. Intra-Cellular Therapies, Inc; 2020.  
10 Data on File. CAPLYTA. Clinical Study Report of Study 501. Intra-Cellular Therapies, Inc; 2024.  
11 Data on File. CAPLYTA. Clinical Study Report of Study 502. Intra-Cellular Therapies, Inc; 2024.  
12 Data on File. CAPLYTA. Clinical Study Report of Study 503. Intra-Cellular Therapies, Inc; 2025.  
13 Correll CU, Davis RE, Weingart M, et al. Efficacy and safety of lumateperone for treatment of schizophrenia: a randomized clinical trial. JAMA Psychiatry. 2020;77(4):349-358.  
14 Vanover K, O’Gorman C, Glass S, et al. Favorable clinical safety profile for lumateperone (ITI-007) - switching from standard-of-care antipsychotic therapy in patients with schizophrenia [abstract]. Schizophr Bull. 2019;45(Suppl 2):S351. Abstract S117.  
15 Correll C, Durgam S, Kozauer S, et al. Lumateperone monotherapy for major depressive episodes associated with bipolar disorder: efficacy and safety in a randomized placebo-controlled trial. Int Clin Psychopharmacol. 2026;41(2):120-129.  
16 Tohen M, Durgam S, Kozauer SG, et al. Long-term safety and tolerability of lumateperone 42 mg in patients with bipolar disorder: results from a 6-month open-label extension study. Int Clin Psychopharmacol. 2026;41(2):130-137.  
17 Suppes T, Durgam S, Kozauer SG, et al. Adjunctive lumateperone (ITI‐007) in the treatment of bipolar depression: results from a randomized placebo‐controlled clinical trial. Bipolar Disord. 2023;25(6):478-488.  
18 Calabrese JR, Durgam S, Satlin A, et al. Efficacy and safety of lumateperone for major depressive episodes associated with bipolar I or bipolar II disorder: a phase 3 randomized placebo-controlled trial. Am J Psychiatry. 2021;178(12):1098-1106.  
19 Durgam S, Lakkis H, Kozauer S, et al. Efficacy of lumateperone in depression associated with bipolar II disorder: a pooled analysis of late-phase clinical trials. CNS Spectrums. 2025;30(1):1-7.  
20 Durgam S, Earley WR, Kozauer SG, et al. Lumateperone as adjunctive therapy in patients with major depressive disorder: results from a randomized, double-blind, phase-3 trial. J Clin Psychiatry. 2025;86(4):25m15848.  
21 Durgam S, Earley WR, Kozauer SG, et al. Adjunctive lumateperone in patients with major depressive disorder: results from a randomized, double-blind, phase 3 trial. Am J Psychiatry. 2025;182(12):1072-1082.  
22 Durgam S, Earley WR, Kozauer SG, et al. Long-term adjunctive lumateperone 42 mg treatment in major depressive disorder: results from a 6-month open-label extension study. Eur Neuropsychopharmacol. 2026;108:112786.