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CAPLYTA® (lumateperone)

Medical Information

CAPLYTA- Adverse Events - Somnolence and Sedation

Last Updated: 11/07/2025

SUMMARY

  • Antipsychotics, including CAPLYTA, may cause somnolence, postural hypotension, and motor and sensory instability, which may lead to falls and, consequently, fractures and other injuries.1
  • If patients have a condition (or take concomitant drugs) that could exacerbate these effects, complete fall risk assessments when initiating CAPLYTA treatment and periodically during long-term treatment.1 
  • CAPLYTA, like other antipsychotics, may cause somnolence and has the potential to impair judgment, thinking, and motor skills. Patients should be cautioned about operating hazardous machinery and motor vehicles until they are reasonably certain that therapy with CAPLYTA does not affect them adversely.1

Schizophrenia

  • In a pooled analysis of 3 short-term (4- to 6-week), randomized studies, somnolence/sedation was reported in 24.1% of patients who received CAPLYTA 42 mg vs 10% of patients who received placebo.2
  • In a 6-week, open-label, switching study, somnolence was reported in 6.6% of patients who received CAPLYTA 42 mg.3
  • In a 4-week, placebo-controlled study, the frequency of somnolence was 17.3% for CAPLYTA 42 mg and 4% for placebo; the frequency of sedation was 12.7% for CAPLYTA 42 mg and 5.4% for placebo.4
  • In a 6-week, double-blind, placebo-controlled study, the frequencies of somnolence and sedation, respectively, were 18% and 4.1% for CAPLYTA 42 mg, 17.3% and 8.1% for risperidone 4 mg, and 6.2% and 2.8% for placebo.5
  • In a 1-year, open-label study, the frequency of somnolence leading to discontinuation was 0.7% in patients who received CAPLYTA 42 mg.6

Bipolar Depression

  • In a 6-week, placebo-controlled study, the frequency of somnolence was 8.5% in the CAPLYTA 42 mg group vs 1.1% in the placebo group.7 
  • In a 6-week, adjunctive study with lithium or valproate, the frequency of somnolence was 11.3% in the CAPLYTA 42 mg group and 3.4% in the placebo group.8 
  • In a 6-week, monotherapy study, somnolence was reported in 8.5% of patients in the CAPLYTA 42 mg group vs 1.1% of patients in the placebo group.9 
  • In a 6-month, open-label extension study, somnolence was reported in 8.8% of patients who received CAPLYTA 42 mg.10

Major Depressive Disorder with Mixed Features or Bipolar Depression with Mixed Features

  • In a 6-week, randomized study, the frequency of somnolence in the CAPLYTA 42 mg groups was 12.5% in the combined major depressive disorder (MDD)/bipolar depression population, 12% in the MDD population, and 13% in the bipolar depression population, respectively.11

Major Depressive Disorder

  • In a 6-week, randomized study (study 501), the frequency of somnolence was 4.1% in the CAPLYTA 42 mg+antidepressant therapy (ADT) group vs 1.2% in the placebo+ADT group; the corresponding frequency of sedation was 2.5% vs 0.4%.12 
  • In another 6-week, randomized study (study 502), the frequency of somnolence was 16.1% in the CAPLYTA 42 mg+ADT group vs 2.9% in the placebo+ADT group; the corresponding frequency of sedation was 2.1% vs 0%.13 
  • In a 26-week, open-label study, somnolence was reported in 7.2% of patients who received CAPLYTA 42 mg during the final analysis.14

PRODUCT LABELING

Falls

Antipsychotics, including CAPLYTA, may cause somnolence, postural hypotension, and motor and sensory instability, which may lead to falls and, consequently, fractures and other injuries.1

If patients have a condition (or take concomitant drugs) that could exacerbate these effects, complete fall risk assessments when initiating CAPLYTA treatment and periodically during long-term treatment.1 

Potential for Cognitive and Motor Impairment

CAPLYTA, like other antipsychotics, may cause somnolence and has the potential to impair judgment, thinking, and motor skills. Patients should be cautioned about operating hazardous machinery and motor vehicles until they are reasonably certain that therapy with CAPLYTA does not affect them adversely.1 

CLINICAL DATA


Summary of Clinical Studies of CAPLYTA
Study Objective
Patients and Treatment Groups
Outcomes
Schizophrenia
Kane et al (2021)2 conducted a pooled analysis of 3 short-term (4- to 6-week), randomized studies of patients with schizophrenia.
  • Patients received CAPLYTA 42 mg (n=406) or placebo (n=412).
  • Somnolence/sedation was reported in 24.1% of patients who received CAPLYTA and 10% of patients who received placebo.
Correll et al (2021)3 conducted a 6-week, open-label, switching study to assess the short-term safety and tolerability of CAPLYTA in outpatients with stable schizophrenia who were transitioned from a prior antipsychotic therapy.
  • Patients received CAPLYTA 42 mg once daily in the evening (N=301).
  • Somnolence was reported in 6.6% of patients.
A 4-week, double-blind, placebo-controlled, multicenter study assessed the antipsychotic efficacy of CAPLYTA in patients with schizophrenia experiencing acute exacerbation of psychosis.4
  • Patients were randomized 1:1:1 to receive CAPLYTA 28 mg (n=150), CAPLYTA 42 mg (n=150), or placebo (n=149) once daily.
  • The frequency of somnolence was 11.3% for CAPLYTA 28 mg, 17.3% for CAPLYTA 42 mg, and 4% for placebo.
  • Six patients (4.0%) in the CAPLYTA 28 mg group and 7 patients (4.7%) in the CAPLYTA 42 mg group reported moderate somnolence. All other cases were considered mild.
  • The frequency of sedation was 9.3% for CAPLYTA 28 mg, 12.7% for CAPLYTA 42 mg, and 5.4% for placebo. All cases were considered mild.
A 6-week, double-blind, placebo-controlled, multicenter study assessed the antipsychotic efficacy of CAPLYTA in patients with schizophrenia experiencing an acute exacerbation of psychosis.5
  • Patients were randomized 1:1:1:1 to receive CAPLYTA 14 mg (n=172), CAPLYTA 42 mg (n=172), RIS 4 mg (n=173), or placebo (n=178) once daily.
Treatment Groups
n (%)
CAPLYTA 14 mg
CAPLYTA
42 mg
RIS
4 mg
Placebo
Somnolence
19
(11)
31
(18)
30
(17.3)
11
(6.2)
Sedation
11
(6.4)
7
(4.1)
14
(8.1)
5
(2.8)
  • Four patients (2.3%) in the CAPLYTA 14 mg group, 1 patient (0.6%) in the CAPLYTA 42 mg group, 3 patients (1.7%) in the RIS 4 mg group, and 2 patients (1.1%) in the placebo group reported moderate somnolence. All other cases were considered mild.
  • One patient (0.6%) in the CAPLYTA 14 mg group and 2 patients (1.2%) in the RIS 4 mg group reported moderate sedation. All other cases were considered mild.
A long-term, open-label, multicenter study determined the safety of CAPLYTA 42 mg for up to 1 year in outpatients with schizophrenia.6
  • Patients received CAPLYTA 42 mg once daily in the evening (N=602).
  • The frequency of somnolence leading to discontinuation was 0.7%.
Bipolar depression
Calabrese et al (2021)7 conducted a phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of CAPLYTA for 6 weeks in patients with bipolar I or bipolar II disorder experiencing an MDE.
  • Patients received CAPLYTA 42 mg (n=188) or placebo (n=189) once daily in the evening.
  • The frequency of somnolence was 8.5% in the CAPLYTA group vs 1.1% in the placebo group.
  • Somnolence was severe in 1 patient (0.5%) in the CAPLYTA group.
Suppes et al (2023)8conducted a phase 3, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of CAPLYTA for 6 weeks adjunctive to lithium or valproate in patients with bipolar I or bipolar II disorder experiencing an MDE.
  • Patients were randomized 1:1:1 to receive CAPLYTA 28 mg (n=176), CAPLYTA 42 mg (n=177), or placebo (n=176) once daily in the evening; this was followed by a 2-week safety follow-up period.
  • The frequency of somnolence was 7.4% (n=13) in the CAPLYTA 28 mg group, 11.3% (n=20) in the CAPLYTA 42 mg group, and 3.4% (n=6) in the placebo group.
  • The mean duration of somnolence in all groups ranged from 16 to 21 days.
A phase 3, randomized, double-blind, placebo-controlled, multicenter study assessed the efficacy and safety of CAPLYTA monotherapy for 6 weeks in patients with MDEs associated with bipolar I or bipolar II disorder (bipolar depression).9
  • Patients were randomized 1:1 to receive CAPLYTA 42 mg (n=188) or placebo (n=189) once daily in the evening.
  • Somnolence was reported by 16 patients (8.5%) in the CAPLYTA group vs 2 patients (1.1%) in the placebo group.
  • In the CAPLYTA group, treatment was discontinued due to somnolence and sedation by 1 patient (0.5%) each.
A 6-month open-label extension of a 6-week, phase 3, randomized, double-blind, placebo-controlled, multicenter study determined the safety and tolerability of CAPLYTA monotherapy in patients with MDEs associated with bipolar I or bipolar II disorder (bipolar depression).10 
  • Patients received CAPLYTA 42 mg (N=127) once daily in the evening.
  • Somnolence was reported by 11 patients (8.8%) in the CAPLYTA group.
MDD with mixed features or bipolar depression with mixed features
Durgam et al (2025)11 conducted a 6-week, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of CAPLYTA in patients with MDD with mixed features (n=185) and those with bipolar depression with mixed features (n=200) and an MDE.
  • Patients were randomized 1:1 to receive CAPLYTA 42 mg (n=193) or placebo (n=195).
  • The frequency of somnolence is summarized in the tables below.
Combined MDD/Bipolar Depression Population
TEAE, n (%)
CAPLYTA
(n=192)
Placebo
(n=193)
Somnolence
24 (12.5)
3 (1.6)
MDD Population
TEAE, n (%)
CAPLYTA
(n=92)
Placebo
(n=93)
Somnolence
11 (12.0)
1 (1.1)
Bipolar Depression Population
TEAE, n (%)
CAPLYTA
(n=100)
Placebo
(n=100)
Somnolence
13 (13.0)
2 (2.0)
MDD
A 6-week, randomized, double-blind, placebo-controlled, multicenter study assessed the efficacy and safety of CAPLYTA as adjunctive treatment to ADT in patients with MDD (study 501).12
  • Patients were randomized 1:1 to receive CAPLYTA 42 mg+ADT (n=241) or placebo+ADT (n=243) once daily in the evening.
  • Somnolence occurred in 10 patients (4.1%) in the CAPLYTA+ADT group vs 3 patients (1.2%) in the placebo+ADT group.
  • Sedation occurred in 6 patients (2.5%) in the CAPLYTA+ADT group vs 1 patient (0.4%) in the placebo+ADT group.
  • Sedation led to treatment discontinuation in 2 patients (0.8%) in the CAPLYTA+ADT group vs no patients in the placebo+ADT group.
A 6-week, randomized, double-blind, placebo-controlled, multicenter study assessed the efficacy and safety of CAPLYTA as adjunctive treatment to ADT in patients with MDD (study 502).13
  • Patients were randomized 1:1 to receive CAPLYTA 42 mg+ADT (n=242) or placebo+ADT (n=238) once daily in the evening.
  • Somnolence occurred in 39 patients (16.1%) in the CAPLYTA+ADT group vs 7 patients (2.9%) in the placebo+ADT group.
  • Sedation occurred in 5 patients (2.1%) in the CAPLYTA+ADT group vs no patients in the placebo+ADT group. Severe sedation was reported in 1 patient in the CAPLYTA+ADT group.
  • Somnolence and sedation, respectively, led to treatment discontinuation in 3 patients (1.2%) and 1 patient (0.4%) in the CAPLYTA+ADT group vs 0 patients and 0 patients in the placebo+ADT group.
A 26-week, open-label, multicenter study evaluated the safety and tolerability of CAPLYTA 42 mg as adjunctive treatment to ADT in patients with MDD. Patients who safely completed study 501 or study 502 were eligible to participate in this study.14 
  • Patients received CAPLYTA 42 mg+ADT (N=809) once daily in the evening.
  • Somnolence occurred in 58 patients (7.2%) during the final analysis.
  • Severe somnolence and sedation were reported in 1 patient each.
  • Somnolence led to treatment discontinuation in 6 patients (0.7%).
Abbreviations: ADT, antidepressant therapy; MDD, major depressive disorder; MDE, major depressive episode; RIS, risperidone; 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 18 September 2025.

References

Show
1 CAPLYTA (lumateperone) [Prescribing Information]. Bedminster, NJ: Intra-Cellular Therapies, Inc; https://www.intracellulartherapies.com/docs/caplyta_pi.pdf
2 Kane JM, Durgam S, Satlin A, et al. Safety and tolerability of lumateperone for the treatment of schizophrenia: a pooled analysis of late-phase placebo- and active-controlled clinical trials. Int Clin Psychopharmacol. 2021;36(5):244-250.  
3 Correll CU, Vanover KE, Davis RE, et al. Safety and tolerability of lumateperone 42 mg: an open-label antipsychotic switch study in outpatients with stable schizophrenia. Schizophr Res. 2021;228:198-205.  
4 Data on File. CAPLYTA. Clinical Study Report of Study 301. Intra-Cellular Therapies, Inc; 2016.  
5 Data on File. CAPLYTA. Clinical Study Report of Study 302. Intra-Cellular Therapies, Inc; 2017.  
6 Data on File. CAPLYTA. Clinical Study Report of Study 303. Intra-Cellular Therapies, Inc; 2025.  
7 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.  
8 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.  
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 401. Intra-Cellular Therapies, Inc; 2021.  
11 Durgam S, Kozauer SG, Earley WR, et al. Lumateperone for the treatment of major depressive disorder with mixed features or bipolar depression with mixed features: a randomized placebo-controlled trial. J Clin Psychopharmacol. 2025;45(2):67-75.  
12 Data on File. CAPLYTA. Clinical Study Report of Study 501. Intra-Cellular Therapies, Inc; 2024.  
13 Data on File. CAPLYTA. Clinical Study Report of Study 502. Intra-Cellular Therapies, Inc; 2024.  
14 Data on File. CAPLYTA. Final Clinical Study Report of Study 503. Intra-Cellular Therapies, Inc; 2025.