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CAPLYTA® (lumateperone)

Medical Information

CAPLYTA - Adverse Event - Suicide

Last Updated: 11/10/2025

SUMMARY

  • 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

Schizophrenia

  • In a randomized, double-blind, placebo-controlled, phase 2 study of patients with schizophrenia, suicidal ideation was reported in 1 patient each in the lumateperone 84 mg, risperidone, and placebo groups.2
  • In a randomized, double-blind, placebo-controlled, phase 3 study (study 301) evaluating lumateperone 28 mg and CAPLYTA 42 mg in patients with schizophrenia:3
    • Suicidal ideation was reported in 1.4% of patients in each group during the 4-week treatment period and in 0.7%, 1.4%, and 2.2% of patients in the lumateperone 28 mg, CAPLYTA 42 mg, and placebo groups, respectively, during the posttreatment period.
  • In a randomized, double-blind, placebo- and active-controlled, phase 3 study (study 302) evaluating lumateperone 14 mg and CAPLYTA 42 mg versus risperidone and placebo in patients with schizophrenia:4
    • During the 6-week 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, while suicidal behavior occurred in 0.6% of patients in each of the lumateperone 14 mg and CAPLYTA 42 mg groups.
    • During the posttreatment period, suicidal ideation was reported in 0.6% of patients in the placebo group.
  • In an open-label, multicenter study (study 303) evaluating the long-term safety of CAPLYTA 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 treatment.13 

Bipolar Depression

  • In a phase 3, randomized, double-blind, placebo-controlled study (study 401) evaluating monotherapy with lumateperone 28 mg and CAPLYTA 42 mg in patients with major depressive episodes (MDEs) associated with bipolar I or II disorder:6
    • During the 6-week treatment period, emergence of suicidal ideation occurred in 8.9%, 4.9%, and 9.2% of patients receiving lumateperone 28 mg, CAPLYTA 42 mg, and placebo, respectively.
    • During the posttreatment period, suicidal behavior was reported in 1 and 2 patients in the lumateperone 28 mg and CAPLYTA 42 mg groups, respectively.
    • During the open-label extension (OLE) 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.
  • In another phase 3, randomized, double-blind, placebo-controlled study (study 402) evaluating lumateperone 28 mg and CAPLYTA 42 mg as adjunctive therapy to lithium or valproate in patients with MDEs associated with bipolar I or II disorder:7
    • During the 6-week treatment period, emergence of suicidal ideation occurred in 1.2%, 0.6%, and 4.1% of patients in the lumateperone 28 mg, CAPLYTA 42 mg, and placebo groups, respectively.
  • In a phase 3, randomized, double-blind, placebo-controlled study (study 403) evaluating CAPLYTA monotherapy in patients with MDEs associated with bipolar I or II disorder or major depressive disorder (MDD):8
    • Suicidal ideation was reported in 6.3% of CAPLYTA-treated patients and 8% of placebo patients during the 6-week treatment period, with no suicidal behavior observed.
  • In a phase 3, randomized, double-blind, placebo-controlled study (study 404) evaluating CAPLYTA 42 mg for the treatment of MDEs associated with bipolar I or II disorder:14
    • During the 6-week treatment period, the proportion of patients reporting suicidal ideation increased from 4.3% at baseline to 5.3% in the CAPLYTA group and from 7.9% at baseline to 10.1% in the placebo group.
  • In a prespecified secondary and post hoc analyses of study 404 evaluating CAPLYTA 42 mg in patients with bipolar I or II disorder experiencing an MDE:15
    • From baseline to day 43, the Montgomery-Åsberg Depression Rating Scale (MADRS) item of suicidal thoughts significantly improved with CAPLYTA compared with placebo (least squares mean change -0.3 vs -0.1; P <0.01), with similar improvements in the bipolar I (-0.3 vs -0.2; P <0.05) and bipolar II (-0.3 vs 0; P <0.05) populations.

MDD

  • In a phase 3, randomized, double-blind, placebo-controlled study (study 501) evaluating CAPLYTA 42 mg adjunctive to antidepressant therapy (ADT) in patients with major depressive disorder who had an inadequate response to ADT:10,16
    • Suicidal ideation during the 6-week treatment period was reported in 5.5% of CAPLYTA 42 mg+ADT-treated patients and 6.2% of placebo patients, with emergence of suicidal ideation in 1.4% and 3.5% of patients, respectively. 
  • In another phase 3, randomized, double-blind, placebo-controlled study (study 502) evaluating CAPLYTA 42 mg adjunctive to ADT in patients with MDD:11
    • Suicidal ideation and emergence of suicidal ideation were reported in 6.1% and 1.9% of CAPLYTA 42 mg+ADT‑treated patients versus 6.8% and 1.4% of placebo patients during the 6-week treatment period. 
  • In an open-label, multicenter study (study 503) evaluating CAPLYTA as adjunctive treatment to ADT in patients with MDD:12 
    • 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.

PRODUCT LABELING

Suicidal Thoughts and Behaviors

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 

Suicidal Thoughts and Behaviors in Pediatric and Adult Patients

In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other antidepressant classes) that included approximately 77,000 adult patients and 4500 pediatric patients, the incidence of suicidal thoughts and behaviors in antidepressant‑treated pediatric and young adults was greater than in placebo-treated patients. There were differences in absolute risk of suicidal thoughts and behaviors across the different uses, with the highest incidence in patients with MDD. The drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1000 patients treated are provided in Table: Risk Differences of the Number of Patients With Suicidal Thoughts and Behaviors in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric and Adult Patients.1


Risk Differences of the Number of Patients With Suicidal Thoughts and Behaviors in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatrica and Adult Patients1
Age Range
Drug-Placebo Difference in Number of Patients of Suicidal Thoughts or Behaviors per 1000 Patients Treated
Increases Compared to Placebo
<18 years old
14 additional patients
18-24 years old
5 additional patients
Decreases Compared to Placebo
25-64 years old
1 fewer patient
≥65 years old
6 fewer patients
aCAPLYTA is not approved for use in pediatric patients.

It is unknown whether the risk of suicidal thoughts and behaviors in pediatric and young adults extends to longer-term use, i.e., beyond four months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with MDD that antidepressants delay the recurrence of depression and that depression itself is a risk factor for suicidal thoughts and behaviors.1

Monitor all antidepressant-treated patients, especially during the initial few months of anti‑depressant drug therapy, and at times of dosage changes. Counsel family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider. Consider changing the therapeutic regimen, including possibly discontinuing CAPLYTA, in patients whose depression is persistently worse, or who experience suicidal thoughts or behaviors.1

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.
A randomized, double‑blind, placebo‑controlled, multicenter, phase 3 study (study 301) 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)13 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 
  • 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.
A randomized, double‑blind, placebo‑controlled, multicenter, phase 3 study (study 402) 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 and placebo groups, respectively.
  • No suicidal behavior was reported during the treatment period.
Calabrese et al (2021)9,14 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 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 and placebo groups, respectively.
McIntyre et al (2023)15 conducted prespecified secondary and post hoc analyses of study 404, a phase 3, randomized, double-blind, placebo-controlled study, to assess the effects of CAPLYTA in patients with bipolar I or bipolar II disorder experiencing an MDE.
  • 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.
  • Of the MADRS items, the score for suicidal thoughts showed an LS mean change from baseline to day 43 of -0.3 vs -0.1 (P <0.01) in the CAPLYTA group vs the placebo group.
    • In the bipolar I population, the score for suicidal thoughts showed an LS mean change from baseline to day 43 of -0.3 vs -0.2 (P <0.05) in the CAPLYTA group vs the placebo group.
    • In the bipolar II population, the score for suicidal thoughts showed an LS mean change from baseline to day 43 of -0.3 vs 0 (P <0.05) in the CAPLYTA group vs the placebo group.
MDD
Durgam et al (2025)10,16 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.
A randomized, double‑blind, placebo‑controlled, multicenter, phase 3 study (study 502) 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.
An open-label, multicenter study (study 503) evaluated 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.
  • Suicidal ideation was reported in 4.4% (34/779) of patients, emergence of suicidal ideation in 2.7% (20/736) of patients, and worsening of suicidal ideation in 0.1% (1/773) of patients.
  • No suicidal behavior or emergence of suicidal behavior was reported during the open-label treatment period.
  • During the post open-label treatment period, 1% of patients (8/776) reported suicidal ideation.
Abbreviations: ADT, antidepressant therapy; LS, least squares; MADRS, Montgomery-Åsberg Depression Rating Scale; MDD, major depressive disorder; MDE, major depressive episode.

Literature Search

A literature search of MEDLINE®, EMBASE®, BIOSIS Previews®, and DERWENT® (and/or other resources, including internal/external databases) was conducted on 19 September 2025.

References

Show
1 CAPLYTA (lumateperone) [Prescribing Information]. Bedminster, 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 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.  
14 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.  
15 McIntyre RS, Durgam S, Kozauer SG, et al. The efficacy of lumateperone on symptoms of depression in bipolar I and bipolar II disorder: Secondary and post hoc analyses. Eur Neuropsychopharmacol. 2023;68:78-88.  
16 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.