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(lumateperone)

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CAPLYTA® (lumateperone)

Medical Information

CAPLYTA - Adverse Event - Effects on Prolactin

Last Updated: 11/06/2025

SUMMARY

Schizophrenia

  • In a pooled analysis of 3 randomized, double-blind, placebo-controlled trials in the treatment of schizophrenia, the mean±standard deviation (SD) change in prolactin level from baseline to the last on-treatment value was -1.3±8.86 ng/mL with CAPLYTA vs -0.2±8.46 ng/mL with placebo.1
  • In a 2-part, open-label (OL), multicenter study in patients with schizophrenia, the mean±SD change in prolactin level from baseline to day 368 was -2.67±22.515 µg/L.2

Bipolar Depression

  • In a phase 3, 6-week, randomized, double-blind, placebo-controlled trial in patients with bipolar disorder (study 401), the least squares (LS) mean (standard error [SE]) change in prolactin level from baseline to day 43 was 0.95 (0.48) µg/L in the CAPLYTA 42 mg group and 1.12 (0.46) µg/L in the CAPLYTA 28 mg group.3
  • In a 6-month OL extension of a phase 3 study (study 401), the mean (SE) change in prolactin level from baseline to day 175 in the CAPLYTA 42 mg group was 1.3 (0.58) µg/L; this change was not clinically relevant.4
  • In a phase 3, randomized, double-blind, placebo-controlled, multicenter study in patients with bipolar I or bipolar II disorder who experienced major depressive episode, the mean (SE) change in prolactin level from baseline to week 6 in the CAPLYTA group was -0.8 (1.1) µg/L.5

Major Depressive Disorder

  • In a phase 3, 6-week, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study in patients with major depressive disorder (MDD) who had an inadequate response to antidepressant therapy (ADT; study 501), the mean (SE) change in prolactin level from baseline to end of treatment in the CAPLYTA 42 mg+ADT group was 1.6 (0.76) ng/mL.6
  • In a 26-week OL extension in adult patients with MDD who had completed study 501 or 502, the mean±SD change in prolactin level from baseline to end of treatment in the CAPLYTA 42 mg+ADT group was 1.13±13.01 ng/mL.7
  • In a pooled analysis of studies 501 and 502, the mean±SD change in prolactin level from baseline to end of treatment (week 6) in the CAPLYTA 42 mg+ADT group was 1.1±10.20 ng/mL.8

CLINICAL DATA

Summary of Clinical Studies of CAPLYTA

Study Objective
Patients and Treatment Groups
Outcomes
Schizophrenia
Kane et al (2021)1 conducted a pooled analysis of 3 randomized, double-blind, placebo-controlled trials (studies 005, 301, and 302) to assess the safety and tolerability of CAPLYTA 42 mg in the treatment of schizophrenia.
  • The pooled population comprised of 1073 patients with an acute exacerbation of schizophrenia (CAPLYTA 42 mg, n=406; risperidone 4 mg, n=255; and placebo, n=412).
  • Patients were treated with CAPLYTA for 4 weeks in studies 005 and 301 and for 6 weeks in study 302. Additionally, studies 005 and 302 included risperidone 4 mg as an active control for assay sensitivity.
  • A minor reduction was observed in the mean±SD prolactin level from baseline to the last on-treatment value (CAPLYTA 42 mg, -1.3±8.86 ng/mL; risperidone, 34.9±39.38 ng/mL; placebo, -0.2±8.46 ng/mL).
A 2-part (parts 1 and 2), OL, multicenter study evaluated the safety and effectiveness of CAPLYTA 42 mg in patients with schizophrenia (N=602). Results of part 2 have been reported.2
  • Part 1 involved 6 weeks of treatment with CAPLYTA 42 mg following a switch from standard-of-care antipsychotic therapy. Part 2 included 1 year of treatment and an extension of >1 year.
  • The mean±SD change in prolactin level from baseline to day 368 in patients treated with CAPLYTA (n=534) was -2.67±22.515 µg/L.
Bipolar Depression
Correll et al (2025)3 conducted a phase 3, 6-week, randomized, double-blind, placebo-controlled, outpatient, multicenter study (study 401) to assess the efficacy and safety of CAPLYTA in patients with MDE associated with bipolar I or bipolar II disorder.
  • Patients were randomized (1:1:1) to receive CAPLYTA 28 mg (n=180), CAPLYTA 42 mg (n=184), or placebo (n=185) for 6 weeks; this was followed by a 2-week safety follow-up period.
No notable changes in prolactin were observed in any treatment group:
CAPLYTA 42 mg
(n=184)
CAPLYTA 28 mg
(n=180)
Placebo (n=185)
Baseline Mean±SD
LS Mean (SE) Change at EOT
Baseline Mean±SD
LS Mean (SE) Change at EOT
Baseline Mean±SD
LS Mean (SE) Change at EOT
Prolactin, μg/L
9.5±16.22
0.95 (0.48)a
8.5±9.62
1.12 (0.46)b
8.0±7.18
0.37 (0.45)
aDifference vs placebo, P=0.38. Analysis based on the last observation carried forward using an analysis of covariance.
bDifference vs placebo, P=0.25. Analysis based on the last observation carried forward using an analysis of covariance.
Tohen et al (2025)4 presented results from a 6-month OLE of the aforementioned phase 3 study (study 401) by Correll et al (2025)3 assessing the long-term safety of CAPLYTA in patients with MDEs associated with bipolar I or bipolar II disorder.
  • Eligible patients (N=127) received CAPLYTA 42 mg/day for 175 days; of these, in the 6-week randomized part of the study, 40 had received CAPLYTA 28 mg, 43 had received CAPLYTA 42 mg, and 44 had received placebo.
  • The mean (SE) change in prolactin level from baseline to day 175 in patients treated with CAPLYTA (n=121) was 1.3 (0.58) µg/L. No clinically relevant changes were observed.
Calabrese et al (2021)5 conducted a phase 3, randomized, double-blind, placebo-controlled, multicenter study that evaluated the efficacy and safety of CAPLYTA 42 mg in patients with bipolar I or bipolar II disorder who experienced MDEs.
  • Patients received CAPLYTA 42 mg (n=188) or placebo (n=189) once daily for 6 weeks.
  • The mean (SE) change in prolactin level from baseline to week 6 was -0.8 (1.1) µg/L in the CAPLYTA group and 1.7 (1.3) μg/L in the placebo group.
MDD
Durgam et al (2025)6 conducted a phase 3, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study 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.
Changes in prolactin levels at end of treatment were not clinically significant and were generally similar between groups:
CAPLYTA 42 mg+ADT
(n=241)
Placebo+ADT
(n=243)
Baseline Mean±SD
Mean (SE) Change at EOT
Baseline Mean±SD
Mean (SE) Change at EOT
Prolactin, ng/mL
11±14.57
1.6 (0.76)
9.6±8.83
0.6 (0.48)
Earley et al (2025)7 presented a 26-week OL extension study that evaluated the long-term safety and tolerability of CAPLYTA 42 mg as adjunctive therapy to ADT in adult patients with MDD who had completed studies 501 or 502.
  • Adult patients with MDD (N=809).
Change in prolactin level at end of treatment was low and not clinically relevant:
CAPLYTA 42 mg+ADT
(N=809)
Baseline
Mean±SD
Mean±SD
Change From Baseline to EOT
Prolactin, ng/dL
10.07±12.98
1.13±13.01
Kozauer et al (2024)8 presented a pooled analysis of the 6-week studies 501 and 502 that evaluated the safety and tolerability of CAPLYTA 42 mg adjunctive to ADT in patients with MDD with inadequate response to ADT.
  • The safety population included 964 patients (CAPLYTA+ADT, n=483; placebo+ADT, n=481).
Changes in prolactin levels at end of treatment (week 6) were not clinically relevant:
CAPLYTA 42 mg+ADT
(n=483)
Placebo+ADT
(n=481)
Baseline Mean±SD
Mean±SD Change at EOT
Baseline Mean±SD
Mean±SD Change at EOT
Prolactin, ng/mL
10±9.37
1.1±10.20
9.6±14.48
1±8.17
Abbreviations: ADT, antidepressant therapy; EOT, end of treatment; LS, least squares; MDD, major depressive disorder; MDE, major depressive episode; OL, open-label; 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 18 September 2025.

References

Show
1 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.  
2 Data on File. CAPLYTA. Clinical Study Report of Study 303. Intra-Cellular Therapies, Inc; 2025.  
3 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.  
4 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. [published online ahead of print July 16, 2025]. Int Clin Psychopharmacol. doi:10.1097/YIC.0000000000000596.  
5 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.  
6 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.  
7 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.  
8 Kozauer SG, Durgam S, Earley WR, et al. Safety and tolerability of lumateperone 42 mg for the treatment of major depressive disorder: a pooled analysis of 2 randomized placebo-controlled trials. Poster presented at: The 63rd Annual Meeting of the American College of Neuropsychopharmacology (ACNP); December 8-11, 2024; Phoenix, AZ.