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(lumateperone)

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CAPLYTA® (lumateperone)
Medical Information

CAPLYTA - Adverse Event - Somnolence and Sedation

Last Updated: 04/01/2026

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
  • In a pooled analysis of 3 short-term (4- to 6-week), randomized studies in patients with schizophrenia, somnolence/sedation was reported in 24.1% of patients who received CAPLYTA 42 mg vs 10% of patients who received placebo.2
  • In 4- and 6-week clinical trials in patients with schizophrenia, somnolence and/or sedation were reported in ≤18% of patients treated with CAPLYTA 42 mg.3-5
  • In Part 1 of Study 303, an open label switching study in patients with schizophrenia, sedation was reported in 6.6% of patients. In the 1year long term open label phase (Part 2), somnolence resulted in treatment discontinuation in 0.7% of patients receiving CAPLYTA 42 mg.6,7
  • In 3 clinical studies, which includes 1 open label safety study, in patients with major depressive episodes (MDE) associated with bipolar I or II disorder, somnolence was reported in ≤13% of patients treated with CAPLYTA 42 mg.8-12
  • In a 6-week, randomized study in patients with major depressive disorder (MDD) with mixed features or bipolar depression with mixed features, the frequency of somnolence in the CAPLYTA 42 mg groups was 12.5% in the combined MDD/bipolar depression population, 12% in the MDD population, and 13% in the bipolar depression population, respectively.13
  • In two phase 3 clinical trials (Study 501 and Study 502) in MDD patients receiving CAPLYTA 42 mg + ADT, the frequency of somnolence was 4-16% and the frequency of somnolence was 2-3%. In the 26 week open label extension study in MDD, somnolence was reported in 7.2% of patients who received CAPLYTA 42 mg.14-19 
  • In a pooled analysis of Study 501 and Study 502 in patients with MDD, 8.5% of patients receiving CAPLYTA experienced their first onset of somnolence within 1 week. Mean duration of somnolence was 14.6 days.20 

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 42 mg and 10% of patients who received placebo.
Correll et al (2021)6 conducted a 6-week, open label switching study (Part A, Study 303) to assess the short-term safety and tolerability of CAPLYTA in outpatients with stable schizophrenia who were transitioned from a prior antipsychotic therapy; a 1 year long-term open OLE (Part B) followed.7 
  • Part A: Patients received CAPLYTA 42 mg once daily in the evening (N=301).
  • Part B: A total of 602 patients received ≥1 dose of CAPLYTA 42 mg during the 1-Year treatment period.
  • Part A:
    • Somnolence was reported in 6.6% of patients.
  • Part B:
    • The frequency of somnolence leading to discontinuation was 0.7%.
A 4-week, double-blind, placebo-controlled, multicenter study assessed the antipsychotic efficacy of CAPLYTA in patients with schizophrenia experiencing acute exacerbation of psychosis (Study 301).3,5
  • Patients were randomized 1:1:1 to receive lumateperone 28 mg (n=150), CAPLYTA 42 mg (n=150), or placebo (n=149) once daily.
  • The frequency of somnolence was 11.3% for lumateperone 28 mg, 17.3% for CAPLYTA 42 mg, and 4% for placebo.
  • Six patients (4.0%) in the lumateperone 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 lumateperone 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 (Study 302).4
  • Patients were randomized 1:1:1:1 to receive Luma 14 mg (n=172), CAP 42 mg (n=172), RIS 4 mg (n=173), or PBO (n=178) once daily.
Treatment Groups
n (%)
Luma 14 mg
CAP
42 mg
RIS
4 mg
PBO
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 lumateperone 14 mg group, 1 patient (0.6%) in the CAPLYTA 42 mg group, 3 patients (1.7%) in the risperidone 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 lumateperone 14 mg group and 2 patients (1.2%) in the risperidone 4 mg group reported moderate sedation. All other cases were considered mild.
Bipolar depression
Calabrese et al (2021)9 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 (Study 404).
  • 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 42 mg group vs 1.1% in the placebo group.
  • Somnolence was severe in 1 patient (0.5%) in the CAPLYTA 42 mg group.
  • In the CAPLYTA 42 mg group, treatment was discontinued due to somnolence and sedation by 1 patient (0.5%) each.
Suppes et al (2023)10conducted 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 (Study 402).
  • Patients were randomized 1:1:1 to receive lumateperone 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 lumateperone 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 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 bipolar II disorder (bipolar depression).8,12 
  • In Part A, patients were randomized 1:1:1 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:
    • Somnolence was reported in 52 patients (9.5%): lumateperone 28 mg, n=21 (11.7%); CAPLYTA 42 mg, n=24 (13%); placebo, n=7 (3.8%).
  • Part B:
    • Somnolence was reported by 11 patients (8.8%) in the CAPLYTA 42 mg group.
MDD with mixed features or bipolar depression with mixed features
Durgam et al (2025)13 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 (Study 403).
  • Patients were randomized 1:1 to receive CAPLYTA 42 mg (n=193) or placebo (n=195).
Combined MDD/Bipolar Depression Population
TEAE, n (%)
CAP 42 mg
(n=192)
PBO
(n=193)
Somnolence
24 (12.5)
3 (1.6)
MDD Population
TEAE, n (%)
CAP 42 mg
(n=92)
PBO
(n=93)
Somnolence
11 (12)
1 (1.1)
Bipolar Depression Population
TEAE, n (%)
CAP 42 mg
(n=100)
PBO
(n=100)
Somnolence
13 (13)
2 (2)
MDD
Durgam et al (2025)14,15 conducted 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).
  • 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 42 mg + ADT group vs 3 patients (1.2%) in the placebo + ADT group.
  • Sedation occurred in 6 patients (2.5%) in the CAPLYTA 42 mg + 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 42 mg + ADT group vs no patients in the placebo + ADT group.
Durgam et al (2025)16 conducted 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).
  • 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 42 mg + ADT group vs 7 patients (2.9%) in the placebo + ADT group.
  • Sedation occurred in 5 patients (2.1%) in the CAPLYTA 42 mg + ADT group vs no patients in the placebo + ADT group. Severe sedation was reported in 1 patient in the CAPLYTA 42 mg + ADT group.17
  • Somnolence and sedation, respectively, led to treatment discontinuation in 3 patients (1.2%) and 1 patient (0.4%) in the CAPLYTA 42 mg + ADT group vs 0 patients and 0 patients in the placebo + ADT group.17
Earley et al (2025)18,19 presented the results of 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 (Study 503).
  • 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%).
Earley et al (2026)20 presented the results of a pooled analysis of Study 501 and Study 502 evaluated the first onset and duration of TEAEs with CAPLYTA 42 mg + ADT in patients with MDD with an inadequate response to ADT.
  • The pooled safety population included 964 patients: CAPLYTA 42 mg +ADT, n=483; placebo + ADT, n=481
Time to First Onset of Somnolence During Treatment (Safety Population)
n (%)a
CAP 42 mg + ADT
PBO + ADT
≤1 week
41 (8.5)
(N1=483)
7 (1.5)
(N1=481)
>1 and ≤2 weeks
5 (1.1)
(N1=465)
1 (0.2)
(N1=480)
>2 and ≤3 weeks
0
(N1=450)
1 (0.2)
(N1=476)
>3 and ≤4 weeks
1 (0.2)
(N1=437)
0
(N1=472)
>4 and ≤5 weeks
0
(N1=432)
0
(N1=466)
>5 weeks
2 (0.5)
(N1=429)
1 (0.2)
(N1=461)
Duration of Somnolenceb During Treatment (Safety Population)
n (%)
CAP 42 mg + ADT
(n=483)
PBO + ADT
(n=481)
Mean (SD), days
14.6 (13.09)
14.9 (13.4)
Median (range), days
9.5 (1-43)
12 (1-44)
Abbreviations: ADT, antidepressant therapy; CAP, CAPLYTA; Luma, lumateperone; MDD, major depressive disorder; MDE, major depressive episode; OLE, open-label extension; PBO, placebo; RIS, risperidone; TEAE, treatment-emergent adverse event.aN1=the number of patients in the safety population who had treatment duration longer than the start of the time interval. n= the number of patients in the category. Patients with multiple TEAEs are counted only once under the earliest category.bSomnolence includes hypersomnia, sedation, and somnolence.

Literature Search

A literature search of MEDLINE®, EMBASE®, BIOSIS Previews®, and DERWENT® (and/or other resources, including internal/external databases) was conducted on 12 February 2026.

 

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 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 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.  
6 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.  
7 Data on File. CAPLYTA. Clinical Study Report of Study 303. Intra-Cellular Therapies, Inc; 2025.  
8 Data on File. CAPLYTA. Clinical Study Report of Study 401. Intra-Cellular Therapies, Inc; 2021.  
9 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.  
10 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.  
11 Data on File. CAPLYTA. Clinical Study Report of Study 404. Intra-Cellular Therapies, Inc; 2020.  
12 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.  
13 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.  
14 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.  
15 Data on File. CAPLYTA. Clinical Study Report of Study 501. Intra-Cellular Therapies, Inc; 2024.  
16 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.  
17 Data on File. CAPLYTA. Clinical Study Report of Study 502. Intra-Cellular Therapies, Inc; 2024.  
18 Earley WR, Durgam S, Kozauer SG, et al. Long-term adjunctive lumateperone treatment in major depressive disorder: results from a six-month open-label extension study. Poster presented at: American Society of Clinical Psychopharmacology (ASCP) Annual Meeting; May 27-30, 2025; Scottsdale, AZ.  
19 Data on File. CAPLYTA. Final Clinical Study Report of Study 503. Intra-Cellular Therapies, Inc; 2025.  
20 Earley WR, Durgam S, Kozauer SG, et al. First onset and duration of treatment-emergent adverse events in patients with major depressive disorder treated with adjunctive lumateperone 42 mg: a pooled analysis of 2 randomized placebo-controlled trials. Poster presented at: 64th Annual Meeting of the American College of Neuropsychopharmacology (ACNP); January 12-15, 2026; Nassau, Bahamas.