SUMMARY

• A pooled analysis reported treatment-emergent adverse events (TEAEs) related to the reproductive system and breast disorders, including dsymenorrhea and vulvovaginal pruritis in 2 patients each with schizophrenia treated with CAPLYTA 42 mg (n=406).^1,2
• A long-term, open-label study that assessed the safety and effectiveness of CAPLYTA 42 mg administered once daily for up to 1 year in patients with schizophrenia reported 2 patients with benign prostatic hyperplasia and 2 patients with dysmenorrhea (N=603).³
• A phase 3 study that evaluated the efficacy and safety of CAPLYTA 42 mg in patients with bipolar I or bipolar II disorder experiencing a major depressive episode (MDE; n=188) reported amenorrhea and priapism in 1 patient each.^4,5 
• A phase 3 study that assessed the efficacy and safety of CAPLYTA (28 mg or 42 mg) adjunctive to lithium or valproate in patients with MDEs associated with bipolar I or bipolar II disorder reported dysmenorrhea in 1 patient treated with CAPLYTA 42 mg (n=177).^6,7 
• A 6-month open-label extension (OLE) period of a phase 3 study that assessed the long-term safety and tolerability of CAPLYTA 42 mg in patients with MDEs associated with bipolar I or bipolar II disorder (N=127) reported 2 patients with erectile dysfunction, 1 with dysmenorrhea, and 1 with delayed ejaculation.^8,9 
• A randomized, double-blind, placebo-controlled, multicenter study reported amenorrhea and erectile dysfunction in 1 patient each with major depressive disorder (MDD) treated with CAPLYTA 42 mg adjunctive to antidepressant therapy (ADT; n=242).¹⁰ 
• A phase 3 OLE study that assessed the long-term safety and tolerability of CAPLYTA 42 mg adjunctive to ADT in patients with MDD reported a treatment-emergent serious adverse event of postmenopausal hemorrhage in 1 patient during the final analysis.^11,12

CLINICAL DATA

Schizophrenia

Kane et al (2021)¹ conducted a pooled analysis of 3 randomized, double-blind, placebo-controlled studies (studies 005, 301, and 302) to assess the efficacy, safety, and tolerability of CAPLYTA 42 mg in patients with schizophrenia (CAPLYTA 42 mg, n=406; placebo, n=412; risperidone 4 mg, n=255). Patients were treated with CAPLYTA 42 mg once daily for 4 weeks in studies 005 and 301 and for 6 weeks in study 302. Safety was assessed at baseline, weekly on-treatment, and at the end of the study. Safety information is summarized in Table: TEAEs Related to the Reproductive System and Breast Disorders.

A long-term, open-label study assessed the safety and effectiveness of CAPLYTA 42 mg administered once daily for up to 1 year in patients with schizophrenia (N=603).³  Safety information is summarized in Table: TEAEs Related to the Reproductive System and Breast Disorders.

Bipolar Depression

Calabrese et al (2021)^4,5 conducted a phase 3, randomized, placebo-controlled, double-blind, multicenter study (study 404) that evaluated the efficacy and safety of CAPLYTA 42 mg in patients with bipolar I or bipolar II disorder experiencing a MDE (CAPLYTA 42 mg, n=188; placebo, n=189). CAPLYTA 42 mg was administered once daily for 6 weeks. Safety was assessed weekly and approximately 2 weeks after the last study dose. Amenorrhea and priapism were reported in 1 patient each in the CAPLYTA 42 group.

Suppes et al (2023)^6,7 conducted a phase 3, randomized, double-blind, placebo-controlled, multicenter study (study 402) to assess the efficacy and safety of CAPLYTA (28 mg or 42 mg) adjunctive to lithium or valproate in patients with MDEs associated with bipolar I or bipolar II disorder (CAPLYTA 42 mg, n=177; CAPLYTA 28 mg, n=176; placebo, n=175). CAPLYTA was administered once daily for 6 weeks. Safety was assessed weekly and approximately 2 weeks after the last study dose. Dysmenorrhea was reported in 1 patient in the CAPLYTA 42 mg group and erectile dysfunction was reported in 1 patient in the CAPLYTA 28 mg group.

Tohen et al (2025)^8,9 reported the results of a 6-month OLE period of a phase 3 study (study 401) that assessed the long-term safety and tolerability of CAPLYTA 42 mg in patients with MDEs associated with bipolar I or bipolar II disorder (N=127). CAPLYTA 42 mg was administered once daily for up to 175 days; this was followed by a 2-week safety follow-up period. Two patients had erectile dysfunction, 1 had dysmenorrhea, and 1 had delayed ejaculation.  

MDD

A randomized, double-blind, placebo-controlled, multicenter, international study (study 502) assessed 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=238). CAPLYTA 42 mg was administered once daily for 6 weeks; this was followed by a 1-week safety follow-up period.¹⁰

For CAPLYTA 42 mg+ADT vs placebo+ADT, the least squares mean difference in the Sexual Functioning Questionnaire-14 item (CSFQ-14) total score from baseline was 0.4 (95% confidence interval [CI], -0.67 to 1.49; P=0.4592) at week 3 and 2.7 (95% CI, 1.34-4.01; P<0.0001) at week 6. The least squares mean difference in the CSFQ-14 total score from baseline in males and females was -0.2 (95% CI, -2.21 to 1.89; P=0.8798) and 1 (-0.25 to 2.32; P=0.1151), respectively, at week 3 and 1.9 (95% CI, -0.22 to 3.98; P=0.0791) and 3.5 (95% CI, 1.82-5.16; P<0.0001), respectively, at week 6. Amenorrhea and erectile dysfunction were reported in 1 patient each in the CAPLYTA 42 mg+ADT group.

Earley et al (2025)^11,12 conducted a phase 3, OLE study (study 503) to assess the long-term safety and tolerability of CAPLYTA 42 mg adjunctive to ADT in patients with MDD who had completed study 501 or 502 (N=809). CAPLYTA 42 mg was administered once daily for 26 weeks. A treatment-emergent serious adverse event of postmenopausal hemorrhage was reported in 1 patient (0.2%) during the final analysis.  

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.