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 phase 3, 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).^10,11 
• 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.^12,13

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

Durgam et al (2025)¹⁰ conducted a phase 3, randomized, double-blind, placebo-controlled, multicenter, international study (study 502) that 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.

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.¹¹

Earley et al (2025)^12,13 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.