SUMMARY

• The recommended CAPLYTA dosage is 42 mg administered orally once daily with or without food. Dose titration is not required.¹ 
• For patients receiving concomitant moderate or strong cytochrome P450 3A4 (CYP3A4) inhibitors, the recommended dosage is CAPLYTA 21 mg once daily or 10.5 mg once daily, respectively.¹
• For patients with moderate or severe hepatic impairment, the recommended dosage is 21 mg once daily.¹
• CAPLYTA was administered in the morning during short-term schizophrenia studies^2-4  in the evening during long-term schizophrenia studies,⁵ in the evening during studies for bipolar depression,^6,7 and in the evening during studies for major depressive disorder (MDD).^8-10
• Kane et al (2021)¹¹ performed a pooled analysis of 3 randomized, double-blind, placebo-controlled trials to assess the safety and tolerability of CAPLYTA 42 mg in the treatment of schizophrenia. CAPLYTA was dosed in the morning.^2-4 
  • The most common treatment emergent adverse events (TEAEs; ≥5% and twice that with placebo) were somnolence/sedation and dry mouth.¹¹
  • Other TEAEs (≥2% of patients in the CAPLYTA group and greater than placebo) were headache, nausea, constipation, dizziness, blood creatine phosphokinase increased, diarrhea, vomiting, back pain, fatigue, abdominal pain, upper respiratory tract infection, pain in extremity, decreased appetite, and urinary tract infection.
• Correll et al (2020)¹² presented the results of an open-label, long-term study that evaluated the effectiveness and safety of CAPLYTA 42 mg in patients with schizophrenia and stable symptoms (N=602). CAPLYTA was dosed in the evening.⁵ 
  • TEAEs that occurred during the 1-year treatment period in ≥5% of patients were decreased weight, dry mouth, headache, and diarrhea.⁵ 
• Suppes et al (2023)⁶ conducted a phase 3, randomized, double-blind, placebo-controlled, multicenter study comprising a 6-week initial treatment period followed by a 2-week safety follow-up to evaluate the efficacy and safety of CAPLYTA 28 or 42 mg as adjunctive therapy to lithium or valproate in patients with major depressive episodes (MDEs) associated with bipolar I or bipolar II disorder. CAPLYTA was dosed in the evening.
  • TEAEs that occurred in any adjunctive CAPLYTA group in >5% of patients and at more than twice the rate of adjunctive placebo were somnolence, dizziness, and nausea.
• Calabrese et al (2021)⁷ conducted a 6-week, phase 3, randomized, double-blind, placebo-controlled, multinational study to evaluate the efficacy and safety of CAPLYTA in patients with MDEs associated with bipolar I or bipolar II disorder. CAPLYTA was dosed in the evening.
  • TEAEs occurring in the CAPLYTA group in at least 5% of patients and at more than twice the rate of the placebo group were somnolence and nausea.
• 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 antidepressant therapy (ADT) in patients with MDD who had an inadequate response to ADT (study 501). CAPLYTA was dosed in the evening.
  • The most common TEAEs (≥5%, more than twice placebo+ADT) were dry mouth, fatigue, and tremor.
• A phase 3, 6-week, randomized, double-blind, placebo-controlled, multicenter study evaluated the efficacy and safety of CAPLYTA 42 mg adjunctive to ADT in patients with MDD who had an inadequate response to ADT (study 502). CAPLYTA was dosed in the evening.⁹
  • The most common TEAEs (≥5%, twice the rate of placebo) were dizziness, somnolence, dry mouth, nausea, diarrhea, and fatigue.
• Earley et al (2025)¹⁰ presented the results of a 26-week open-label extension (OLE) 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 study 501 or 502. CAPLYTA was dosed in the evening.
  • TEAEs that occurred in ≥5% of patients were headache, dizziness, dry mouth, nausea, somnolence, diarrhea, and nasopharyngitis.

PRODUCT LABELING

Recommended Dosage

The recommended CAPLYTA dosage is 42 mg administered orally once daily with or without food. Dose titration is not required.¹

Dosage Recommendations for Concomitant Use with Moderate or Strong CYP3A4 Inhibitors

The recommended CAPLYTA dosage in patients who receive:

• Strong CYP3A4 inhibitors is 10.5 mg once daily.
• Moderate CYP3A4 inhibitors is 21 mg once daily.¹

Dosage Recommendations for Patients with Hepatic Impairment

For patients with moderate hepatic impairment (HI) (Child-Pugh class B) or severe HI (Child-Pugh class C), the recommended CAPLYTA dosage is 21 mg once daily. The recommended CAPLYTA dosage in patients with mild HI is the same as those with normal hepatic function.¹

CLINICAL DATA

• CAPLYTA was administered in the morning during short-term schizophrenia studies,^2-4 in the evening during long-term schizophrenia studies,⁵ in the evening during studies for bipolar depression,^6,7 and in the evening during studies for MDD.^8-10 

Schizophrenia

Kane et al (2021)¹¹ 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 for the treatment of schizophrenia. The pooled population comprised 1073 patients with an acute exacerbation of schizophrenia (CAPLYTA 42 mg [n=406], risperidone 4 mg [n=255], or 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. CAPLYTA was dosed in the morning.^2-4

• The most common TEAEs (incidence of ≥5% and twice that with placebo) were somnolence/sedation and dry mouth.¹¹
• TEAEs (occurring in ≥2% of the CAPLYTA group and greater than placebo) are shown in Table: TEAEs Occurring in ≥2% of Patients in the CAPLYTA Group and Greater Than Placebo in Pooled Trials in Schizophrenia

Correll et al (2020)¹² presented the results of an open-label, long-term study that evaluated the effectiveness and safety of CAPLYTA 42 mg in patients with schizophrenia and stable symptoms for up to 1 year (N=602). CAPLYTA was dosed in the evening.⁵  

• TEAEs that occurred during the 1-year treatment period in ≥5% of patients are presented in Table: Common TEAEs (≥5%) – 1-Year Treatment Period.

Bipolar Depression

Suppes et al (2023)⁶ conducted a phase 3, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of CAPLYTA as adjunctive therapy to lithium or valproate in patients with MDEs associated with bipolar I or bipolar II disorder. Patients were randomized (1:1:1) to receive CAPLYTA 28 mg (n=176), CAPLYTA 42 mg (n=177), or placebo (n=175) for 6 weeks; this was followed by a 2-week safety follow-up period. CAPLYTA was dosed in the evening.

• TEAEs that occurred in any adjunctive CAPLYTA group in >5% of patients and at more than twice the rate of adjunctive placebo were somnolence, dizziness, and nausea. Table: Most Common TEAEs (>5% in the CAPLYTA Group) – Therapy Adjunctive to Lithium or Valproate presents the most common TEAEs (>5% in the adjunctive CAPLYTA group).

Calabrese et al (2021)⁷ conducted a 6-week, phase 3, randomized, double-blind, placebo-controlled, multinational study to evaluate the efficacy and safety of CAPLYTA in patients with MDEs associated with bipolar I or bipolar II disorder. CAPLYTA was dosed in the evening.

• TEAEs occurring in the CAPLYTA group in at least 5% of patients and at more than twice the rate of the placebo group were somnolence (CAPLYTA, 8.5%; placebo, 1.1%) and nausea (CAPLYTA, 6.4%; placebo, 2.1%).

MDD

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 (study 501). Patients were randomized (1:1) to receive CAPLYTA 42 mg (n=242) or placebo (n=243) as adjunctive therapy to ADT for 6 weeks, followed by a 1-week safety follow-up period. CAPLYTA was dosed in the evening.

• The most common TEAEs (≥5%, more than twice placebo+ADT) were dry mouth (CAPLYTA+ADT, 10.8%; placebo+ADT, 2.1%), fatigue (CAPLYTA+ADT, 9.5%; placebo+ADT, 2.1%), and tremor (CAPLYTA+ADT, 5%; placebo+ADT, 0.4%).

A phase 3, 6-week, randomized, double-blind, placebo-controlled, multicenter study evaluated the efficacy and safety of CAPLYTA 42 mg adjunctive to ADT in patients with MDD who had an inadequate response to ADT (study 502). Patients were randomized (1:1) to receive CAPLYTA 42 mg (n=242) or placebo (n=238) as adjunctive therapy to ADT for 6 weeks, followed by a 1-week safety follow-up period. CAPLYTA was dosed in the evening.⁹

• The most common TEAEs (≥5%, twice the rate of placebo) are noted in Table: TEAEs in ≥5% in the CAPLYTA 42 mg+ADT Group and More Than Twice That of the Placebo+ADT Group.

Earley et al (2025)¹⁰ presented the results of 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. Patients (N=809) were administered CAPLYTA 42 mg once daily in the evening.

• TEAEs that occurred in ≥5% of patients are noted in Table: TEAEs Occurring in ≥5% of Patients.

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.