SUMMARY

• In patients with pre-existing low white blood cell count (WBC) or history of leukopenia or neutropenia, perform complete blood counts (CBC). Consider discontinuing CAPLYTA if clinically significant decline in WBC occurs in absence of other causative factors. Discontinue CAPLYTA in patients with clinically significant neutropenia or ANC <1000/mm³ and monitor closely until the neutropenia resolve.¹ 
• Durgam et al (2025)² 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 major depressive disorder (MDD) who had an inadequate response to ADT.
  • The proportion of patients who met potentially clinically significant (PCS) criteria for leukocytes and neutrophils was comparable between treatment groups. PCS criteria for leukocytes ≤2.5×10³ cells/µL and ≥15×10³ cells/µL were reported in 0.4% and 0.9% of patients in the CAPLYTA 42 mg+ADT group and in 1.3% and 0.9% of patients in the placebo+ADT group, respectively. Neutrophils <1.0×10³ cells/µL was reported in 0.9% of patients in the CAPLYTA 42 mg+ADT group and 1.3% of patients in the placebo+ADT group.³ 
• 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.⁴
  • No patients in either group met PCS criteria for neutrophils, or for the PCS-low criterion for leukocytes. Leukocytes ≥15×10³ cells/µL was reported in 0.5% of patients in the CAPLYTA 42 mg+ADT group and 1.3% of patients in the placebo+ADT group.⁵
• Earley et al (2025)⁶ presented results from 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.
  • Few patients met PCS criteria for hematology laboratory values. At the final analysis, leukocytes ≤2.5×10³ cells/µL and ≥15×10³ cells/µL were reported in 0.9% and 1.3% of patients, respectively. Neutrophils <1.0×10³ cells/µL was observed in 0.8% of patients. Treatment-emergent adverse events (TEAEs) related to hematologic changes included decreased WBC count (0.2%) and neutropenia (0.1%).⁷
• Tohen et al (2025)⁸ presented results from a 6-month OLE of a phase 3 study assessing the long-term safety of CAPLYTA 42 mg in patients with major depressive episodes (MDEs) associated with bipolar I or bipolar II disorder.
  • One patient had leukocytes ≥16×10³ cells/µL during the treatment period.⁹
• Suppes et al (2023)¹⁰ conducted a 6-week, phase 3, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of CAPLYTA (28 mg or 42 mg) as adjunctive treatment to lithium or valproate in patients with MDEs associated with bipolar I or bipolar II disorder.
  • One patient in the adjunctive placebo group and 2 patients in the adjunctive CAPLYTA 42 mg group met the pre-specified outlier criterion for leukocytes ≤2.8×10³ cells/μL, and 1 patient in the adjunctive CAPLYTA 42 mg group met the pre-specified outlier criterion for leukocytes ≥16×10³ cells/μL.¹¹
• Calabrese et al (2021)¹² 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.
  • Three patients in the placebo group met outlier criteria for eosinophils/leukocytes (≥10%), 1 patient in the CAPLYTA group and 3 patients in the placebo group met outlier criteria for decreased leukocytes (≤2.8×10³ cells/μL), 1 patient in the placebo group met outlier criteria for increased leukocytes (≥16×10³ cells/μL), and 1 patient in the placebo group met outlier criteria for decreased neutrophils/total cells (≤15%).¹³
• Correll et al (2020)¹⁴ conducted a 12-month, open-label study to evaluate the safety and efficacy of CAPLYTA 42 mg in patients with stable symptoms of schizophrenia. A total of 602 patients received at least one dose of CAPLYTA.
  • The number of patients who met outlier criteria for hematology values was small.¹⁵

PRODUCT LABELING

Leukopenia, Neutropenia, and Agranulocytosis

Leukopenia and neutropenia have been reported during treatment with antipsychotic drugs, including CAPLYTA. Agranulocytosis (including fatal cases) has been reported other with other antipsychotic drugs.¹

Possible risk factors for antipsychotic drug-leukopenia and neutropenia include pre-existing low white blood cell count (WBC) or absolute neutrophil count (ANC) and history of drug-induced leukopenia or neutropenia.¹

In patients with a pre-existing low WBC or ANC or a history of drug-induced leukopenia or neutropenia, perform complete blood count (CBC) monitoring during the first few months of CAPLYTA therapy. Consider discontinuing CAPLYTA in patients who have a clinically significant decline in WBC in the absence of other causative factors. Discontinue CAPLYTA in patients with clinically significant neutropenia or ANC <1000/mm³ and monitor closely until the neutropenia resolves.¹

CLINICAL DATA

MDD

Durgam et al (2025)² 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.

• 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.
• The incidence of PCS hematology values was comparable between treatment groups; see Table: Incidence of Patients Who Met Leukocyte and Neutrophil PCS Criteria.

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.⁴

• No patients in either group met PCS criteria for neutrophils, or for the PCS-low criterion for leukocytes.⁵
• Leukocytes ≥15×10³ cells/µL was considered PCS and was reported in 1 patient (0.5%) in the CAPLYTA 42 mg+ADT group (n=208) and 3 patients (1.3%) in the placebo+ADT group (n=227).

Earley et al (2025)⁶ presented results from 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 at final analysis) were administered CAPLYTA 42 mg once daily in the evening for 26 weeks.
• Few patients met PCS criteria for hematology laboratory values.⁷ See Table: Incidence of Patients Who Met Leukocyte and Neutrophil PCS Criteria.
• TEAEs related to hematologic changes were rare, mostly mild in severity, and observed during the open-label treatment period. See Table: Hematology TEAEs.

Bipolar Disorder

Tohen et al (2025)⁸ presented results from a 6-month OLE of a phase 3 study 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.
• One patient had leukocytes ≥16 × 10³ cells/µL during the treatment period.⁹

Suppes et al (2023)¹⁰ 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 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=176) for 6 weeks of adjunctive therapy with lithium or valproate; this was followed by a 2-week safety follow-up period.
• The number of patients who met the prespecified outliner criteria for hematology values was small.¹¹ See Table: Incidence of Patients Who Met Eosinophil, Leukocyte, and Neutrophil Outlier Criteria.

Calabrese et al (2021)¹² conducted a 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. Patients were randomized (1:1) to receive either CAPLYTA 42 mg (n=188) or placebo (n=189) for 6 weeks; this was followed by a 2-week safety follow-up period.

• Three patients (1.6%) in the placebo group met outlier criteria for eosinophils/leukocytes (≥10%). One patient (0.5%) in the CAPLYTA group and 3 patients (1.6%) in the placebo group met outlier criteria for decreased leukocytes (≤2.8×10³ cells/μL). One patient (0.5%) in the placebo group met outlier criteria for increased leukocytes (≥16×10³ cells/μL). One patient (0.5%) in the placebo group met outlier criteria for decreased neutrophils/total cells (≤15%).¹³ 

Schizophrenia

Correll et al (2020)¹⁴ conducted a 12-month, open-label study to evaluate the safety and efficacy of CAPLYTA 42 mg in patients with stable symptoms of schizophrenia. A total of 602 patients received at least one dose of CAPLYTA.

• The number of patients who met outlier criteria for hematology values was small.¹⁵ See Table: Change from Baseline in Eosinophil/Leukocyte and Neutrophil/Leukocyte Laboratory Values – 1-Year Treatment Period.

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.