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CAPLYTA®

(lumateperone)

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CAPLYTA® (lumateperone)

Medical Information

CAPLYTA – Adverse Event – Weight Change

Last Updated: 11/07/2025

SUMMARY

  • Weight gain has been observed with use of antipsychotics. Monitor weight at baseline and frequently thereafter.1 

Schizophrenia

  • A pooled analysis of three randomized, double-blind, placebo-controlled trials (studies 005, 301, and 302) evaluating CAPLYTA 42 mg in patients with schizophrenia reported that the mean (standard deviation [SD]) change in body weight from baseline to the last on-treatment value was similar between the CAPLYTA and placebo groups (CAPLYTA 42 mg: +1.6 kg [2.85]; placebo: +1.3 kg [3.16]), with larger weight gain observed in the risperidone 4 mg group (+2.6 kg [4.73]).2
  • An open-label, multicenter study of adults with schizophrenia receiving CAPLYTA 42 mg reported a mean change in body weight of -2.18 kg (6.040) from baseline to 1 year and a mean (SD) change in body mass index (BMI) over the same period of -0.72 kg/m2 (2.091).3
  • Bipolar Disorder
  • A phase 3, 6-week, randomized, double-blind, placebo-controlled study evaluating CAPLYTA 28 mg and 42 mg in the treatment of major depressive episodes (MDEs) associated with bipolar I or II disorder reported that mean body weight changes were minimal across all groups (CAPLYTA 42 mg, +0.02 kg [2.38]; CAPLYTA 28 mg, +0.20 kg [2.25]; placebo, +0.32 kg [2.15]).4
  • A phase 3, 6-week, randomized, double-blind, placebo-controlled study evaluating CAPLYTA 28 mg and 42 mg as adjunctive therapy with lithium or valproate for bipolar depression reported mean body weight changes were minimal across all groups. CAPLYTA 28 mg showed a mean (SD) change of +0.02 kg (1.4), CAPLYTA 42 mg showed no change (+0.00 kg [1.7]), and placebo showed a change of +0.23 kg (1.9).5
  • A phase 3, 6-week, randomized, double-blind, placebo-controlled, multinational study of adults experiencing a MDE associated with bipolar I or II disorder reported that the mean body weight changes were minimal across groups. The mean (standard error; SE) change in body weight was +0.11 kg (0.1) in the CAPLYTA 42 mg group and +0.03 kg (0.1) in the placebo group.6
  • In a 6-month, open-label extension of a phase 3, randomized, double-blind, placebo-controlled, multicenter study of patients with MDEs associated with bipolar I or bipolar II disorder, CAPLYTA 42 mg monotherapy resulted in a mean (SD) change in body weight of -0.01 kg (3.079) from baseline to day 175 or early termination. The mean (SD) change in BMI over the same period was -0.01 kg/m² (1.037).7
  • Major Depressive Disorder
  • In a phase 3, 6-week, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study evaluating CAPLYTA 42 mg adjunctive to antidepressant therapy (ADT) in patients with major depressive disorder (MDD) who had an inadequate response to ADT, the mean (SE) change from baseline in body weight was similar in both groups at day 43 (CAPLYTA 42 mg+ADT, +0.1 kg [0.11]; placebo+ADT, +0.0 kg [0.10]).8
  • In a phase 3, 6-week, randomized, double-blind, placebo-controlled, multicenter, international study evaluating CAPLYTA 42 mg adjunctive to ADT in patients with MDD who had an inadequate response to ADT, the mean (SD) change in body weight from baseline to end of treatment was -0.2 kg (1.84) in the CAPLYTA 42 mg+ADT group and +0.1 kg (1.76) in the placebo+ADT group.9
  • In a phase 3, 26-week, open-label extension of 809 adults with MDD receiving CAPLYTA 42 mg as adjunctive therapy to ADT, the mean (SD) change in body weight from baseline to end of treatment was -0.16 kg (3.72) and the mean (SD) change in BMI from baseline to end of treatment was -0.05 kg/m2 (1.33).10

PRODUCT LABELING

Weight Gain

  • Weight gain has been observed with use of antipsychotics. Monitor weight at baseline and frequently thereafter.1 

CLINICAL DATA


Summary of Clinical Studies of CAPLYTA in Patients with Schizophrenia
Study design
N
Outcomes
Mean (SD) change in weight, kg
Mean (SD) change in BMI, kg/m2
≥7% weight increase
≥7% weight decrease
Kane et al (2021)2 performed a pooled analysis of 3 randomized, double-blind, placebo-controlled trials (i.e., studies 005, 301, and 302) to assess the safety and tolerability of CAPLYTA 42 mg in the treatment of schizophrenia. Studies 005 and 301 had 28-day CAPLYTA treatment periods, whereas study 302 had a 42-day CAPLYTA treatment period. Studies 005 and 302 included an active control, risperidone 4 mg, for assay sensitivity.
CAPLYTA 42 mg, n=406;
Placebo, n=412; Risperidone 4 mg, n=255
CAPLYTA 42 mg: +1.6 (2.85)
Placebo: +1.3 (3.16)
Risperidone 4 mg: +2.6 (4.73)
Not available
CAPLYTA 42 mg: 9.1%
Placebo: 9.2%
Risperidone 4 mg: 22.0%
CAPLYTA 42 mg: 1.0%
Placebo: 1.8%
Risperidone 4 mg: 2.5%
A 1-year, open-label, multicenter study evaluated the efficacy and safety of CAPLYTA 42 mg in adult patients with schizophrenia.3
CAPLYTA 42 mg, N=602
 -2.18 (6.040)
-0.72 (2.091)
9.2%
25.2%
Abbreviations: BMI, body mass index; SD, standard deviation.

Summary of Clinical Studies of CAPLYTA in Patients with Bipolar Disorder
Study design
N
Outcomes
Mean (SD/SE) change in weight, kg
Mean (SD/SE) change in BMI, kg/m2
≥7% weight increase
≥7% weight decrease
Correll et al (2025)4 conducted a phase 3, 6-week, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of CAPLYTA in the treatment of MDEs associated with bipolar I or II disorder.
CAPLYTA 28 mg, n=180;
CAPLYTA 42 mg, n=184
Placebo, n=185
CAPLYTA 28 mg: +0.20 (SD, 2.25)
CAPLYTA 42 mg: +0.02 (SD, 2.38)
Placebo: +0.32 (SD, 2.15)
Not available
CAPLYTA 28 mg: 0.6%
CAPLYTA 42 mg: 0.6%
Placebo: 3.4%
CAPLYTA 28 mg: 2.3%
CAPLYTA 42 mg: 3.0%
Placebo: 0.6%
Suppes et al (2023)5 conducted a 6-week, 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 depression.
CAPLYTA 28 mg, n=176;
CAPLYTA 42 mg, n=177;
Placebo, n=176
CAPLYTA 28 mg: +0.02 (SD, 1.4)
CAPLYTA 42 mg: +0.00 (SD, 1.7)
Placebo: +0.23 (SD, 1.9)
CAPLYTA 28 mg: +0.01 (SD, 0.5)
CAPLYTA 42 mg: +0.00 (SD, 0.6)
Placebo: +0.09 (SD, 0.7)
CAPLYTA 28 mg: 0%
CAPLYTA 42 mg: 1.7%
Placebo: 1.7%
CAPLYTA 28 mg: 0.6%
CAPLYTA 42 mg: 0.6%
Placebo: 0.6%
Calabrese et al (2021)6 conducted a phase 3, 6-week, randomized, double-blind, placebo-controlled, multinational study to evaluate the efficacy and safety of CAPLYTA 42 mg in adults experiencing a major depressive episode associated with bipolar I or II disorder.
CAPLYTA 42 mg,
n=188; Placebo, n=189
CAPLYTA 42 mg: +0.11 (SE, 0.1)
Placebo: +0.03 (SE, 0.1)
CAPLYTA 42 mg: +0.04 (SE, 0.0)
Placebo: +0.00 (SE, 0.0)
CAPLYTA 42 mg: 1.1%
Placebo: 1.1%
CAPLYTA 42 mg: 1.1%
Placebo: 0%
A 6-month, open-label extension of a phase 3, randomized, double-blind, placebo-controlled, multicenter study evaluated the efficacy and safety of CAPLYTA 42 mg in patients with major depressive episodes (MDEs) associated with bipolar I or bipolar II disorder. Outcomes were obtained at day 175/early termination.7
CAPLYTA 42 mg, N=127
-0.01 (SD, 3.079)
-0.01 (SD, 1.037)
4.8%
5.6%
Abbreviations: BMI, body mass index; MDE, major depressive episode; SD, standard deviation; SE, standard error.

Summary of Clinical Studies of CAPLYTA in Patients with Major Depressive Disorder
Study design
N
Outcomes
Mean (SD/SE) change in weight, kg
Mean (SD/SE) change in BMI, kg/m2
≥7% weight increase
≥7% weight decrease
Durgam et al (2025)8 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.
CAPLYTA 42 mg+ADT, n=242;
Placebo+ADT, n=243
CAPLYTA 42 mg+ADT: +0.1 (SE, 0.11)
Placebo+ADT: +0.0 (SE, 0.10)
CAPLYTA 42 mg+ADT: +0.0 (SE, 0.04)
Placebo+ADT: +0.0 (SE, 0.03)
CAPLYTA 42 mg+ADT: 0.4%
Placebo+ADT: 0.8%
CAPLYTA 42 mg+ADT: 0.4%
Placebo+ADT: 0.4%
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.9 
CAPLYTA 42 mg+ADT, n=242;
Placebo+ADT, n=238
CAPLYTA 42 mg+ADT:
-0.2 (SD, 1.84)
Placebo+ADT: +0.1 (SD, 1.76)
CAPLYTA 42 mg+ADT: -0.1 (SD, 0.65)
Placebo+ADT: +0.0 (SD, 0.63)
CAPLYTA 42 mg+ADT: 0.4%
Placebo+ADT:
1.7%
CAPLYTA 42 mg+ADT: 0.4%
Placebo+ADT: 0.4%
Earley et al (2025)10 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.
CAPLYTA 42 mg+ADT, N=809
-0.16 (SD, 3.72)
-0.05 (SD, 1.33)
8.5%
9.6%
Abbreviations: ADT, antidepressant therapy; BMI, body mass index; MDD, major depressive disorder; OLE, open-label extension; SD, standard deviation; SE, standard error.

Literature Search

A literature search of MEDLINE®, EMBASE®, BIOSIS Previews®, and DERWENT® (and/or other resources, including internal/external databases) was conducted on 23 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 Data on File. CAPLYTA. Clinical Study Report of Study 303. Intra-Cellular Therapies, Inc; 2025.  
4 Correll CU, Durgam S, Kozauer SG, et al. Lumateperone monotherapy for major depressive episodes associated with bipolar disorder: efficacy and safety in a randomized placebo-controlled trial. [published online ahead of print July 23, 2025]. Int Clin Psychopharmacol. doi:10.1097/yic.0000000000000597.  
5 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.  
6 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.  
7 Data on File. CAPLYTA. Clinical Study Report of Study 401. Intra-Cellular Therapies, Inc; 2021.  
8 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.  
9 Data on File. CAPLYTA. Study 502. Intra-Cellular Therapies, Inc; 2025.  
10 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.