CAPLYTA - Effect on Blood Pressure

SUMMARY

• In a 26-week open-label (OL) extension of 2 phase 3 studies (Study 501 and Study 502) in patients with major depressive disorder (MDD), mean changes in blood pressure and pulse rate in patients treated with CAPLYTA  42  mg adjunctive to antidepressant therapy (ADT) were small and not clinically relevant.¹
• In a 6-month OL extension of a phase 3 study in patients with major depressive episodes (MDEs) associated with bipolar I or bipolar II disorder, mean changes from baseline observed in blood pressure and pulse rate in the CAPLYTA 42 mg group were not clinically relevant.²
• In a phase 3 study in patients with MDEs associated with bipolar I or bipolar II disorder, CAPLYTA  42  mg adjunctive to lithium or valproate was associated with minimal changes from baseline to day 43 in systolic blood pressure (-0.1 mm Hg), diastolic  blood  pressure (-0.3 mm Hg), and pulse rate (-1 bpm).³
• In another phase 3 study in patients with MDEs associated with bipolar I or bipolar II disorder, CAPLYTA 42 mg was associated with minimal changes from baseline to day 43 in systolic (-‍0.53 mm Hg) and diastolic (-0.83 mm Hg) blood pressure and pulse rate (0.76 bpm). No patients had treatment-emergent adverse events (TEAEs) related to an increased or a decreased blood pressure.⁴
• In a pooled analysis of 3 trials in patients with schizophrenia, CAPLYTA 42 mg was associated with minimal changes in mean systolic (-1.1 mm Hg) and diastolic (0.3 mm Hg) blood pressure.⁵
• In a phase 3 study in patients with schizophrenia, orthostatic hypotension was reported in 1 patient in the CAPLYTA 42 mg group and led to treatment discontinuation.⁶
• In a 6-week OL study in patients with schizophrenia, no changes in multipositional blood pressure, heart rate, or incidence of orthostasis were reported with CAPLYTA 42 mg.⁷

PRODUCT LABELING

Orthostatic Hypotension and Syncope

Atypical antipsychotics cause orthostatic hypotension and syncope. Generally, the risk is greatest during initial dose administration.⁸

Orthostatic vital signs should be monitored in patients who are vulnerable to hypotension (e.g., elderly patients, patients with dehydration, hypovolemia, and concomitant treatment with antihypertensive drugs), patients with known cardiovascular disease (history of myocardial infarction, ischemic heart disease, heart failure, or conduction abnormalities), and patients with cerebrovascular disease. CAPLYTA has not been evaluated in patients with a recent history of myocardial infarction or unstable cardiovascular disease. Such patients were excluded from premarketing clinical trials.⁸

CLINICAL DATA

MDD, Adjunctive Therapy to Antidepressants

Durgam et al (2026)¹ presented a 26-week OL study that evaluated the long-term safety and tolerability of CAPLYTA 42 mg adjunctive to ADT in adult patients with MDD who had completed a 6-week, double-blind, placebo-controlled study (study 501 or 502; N=809).

• Mean changes from baseline in blood pressure and pulse rate were minimal¹; see Table: Changes from Baseline to the End of the Open-Label Treatment Period in Blood Pressure and Pulse Rate.

Bipolar Disorder

Tohen et al (2025)² conducted a 6-month OL extension of a phase 3, 6-week, double-blind, placebo-controlled study assessing the long-term safety of CAPLYTA 42 mg in patients with MDEs associated with bipolar I or bipolar II disorder (N=127).

• Changes from baseline observed in blood pressure and pulse rate were not clinically relevant.

Suppes et al (2023)¹⁰ conducted a phase 3, 6-week, randomized, double-blind, placebo-controlled, multicenter study evaluated the efficacy and safety of CAPLYTA adjunctive to lithium or valproate in patients with MDEs associated with bipolar I or bipolar II disorder (safety population; lumateperone 28 mg, n=176; CAPLYTA 42 mg, n=177; placebo, n=175).

• Postbaseline changes observed in blood pressure and pulse rate were small and similar across treatment groups³; see Table: Change from Baseline in Blood Pressure and Pulse Rate.

Calabrese et al (2021)¹¹ conducted a phase 3, 6-week, randomized, double-blind, placebo-controlled, multicenter study evaluated the efficacy and safety of CAPLYTA 42 mg in patients with MDEs associated with bipolar I or bipolar II disorder (safety population; CAPLYTA 42 mg, n=188; placebo, n=189).

• Minimal mean changes in blood pressure and pulse rate were reported, and changes were similar between treatment groups⁴; see Table: Changes from Baseline to the End of the Treatment Period in Blood Pressure and Pulse Rate.
• No patients had TEAEs related to an increased or a decreased blood pressure.⁴

Schizophrenia

Kane et al (2021)⁵ 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 (CAPLYTA 42 mg, n=406; risperidone 4 mg, n=255; placebo, n=412). Patients were treated with CAPLYTA 42 mg 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.

• Minimal changes in systolic and diastolic blood pressure were reported with CAPLYTA 42 mg, and the changes were similar to those reported with placebo⁵; see Table: Changes from Baseline to the Last On-Treatment Value in Blood Pressure and Pulse Rate.

Correll et al (2020)⁶ conducted a phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of CAPLYTA in patients with schizophrenia. Patients were randomized (1:1:1) to receive lumateperone 28 mg (n=150), CAPLYTA 42 mg (n=150), or placebo (n=149) for 4 weeks; this was followed by a 2-week safety follow-up period.

• Orthostatic hypotension was reported in 1 patient in the CAPLYTA 42 mg group and led to treatment discontinuation.

Vanover et al (2017)⁷ presented a 6-week OL study that evaluated the safety of CAPLYTA 42 mg in patients with schizophrenia (N=302). After 6 weeks of treatment, patients were switched back to standard-of-care antipsychotic therapy; they were re-evaluated approximately 2 weeks after the last dose of CAPLYTA 42 mg.

• No changes in multipositional blood pressure, heart rate, or incidence of orthostasis were reported in the study.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 07 April 2026.