SUMMARY

• A 26-week open-label (OL) study evaluated the long-term safety and tolerability of CAPLYTA 42 mg adjunctive to antidepressant therapy (ADT) in adult patients with major depressive disorder (MDD) who had completed a 6-week, double-blind, placebo-controlled study (study 501 or 502).¹ 
  • Mean changes reported in blood pressure were small and not clinically relevant.
• A 6-month OL extension of a phase 3, 6-week, double-blind, placebo-controlled study assessed the long-term safety of CAPLYTA 42 mg in patients with major depressive episodes (MDEs) associated with bipolar I or bipolar II disorder.²  
  • Changes from baseline observed in blood pressure and pulse rate were not clinically relevant.
• 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.³
  • Mean changes from baseline to day 43 observed in systolic (CAPLYTA 28 mg, 0.0 mm Hg; CAPLYTA 42 mg, -0.1 mm Hg; placebo, -0.2 mm Hg) and diastolic (CAPLYTA 28 mg, -0.9 mm Hg; CAPLYTA 42 mg, -0.3 mm Hg; placebo, 0.3 mm Hg) blood pressure and pulse rate (CAPLYTA 28 mg, -0.8 beats per minute [bpm]; CAPLYTA 42 mg, -1.0 bpm; placebo, -0.6 bpm) were small and similar across treatment groups.
• 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.⁴ 
  • Mean changes from baseline to day 43 observed in systolic (CAPLYTA, -‍0.53 mm Hg; placebo, 0.82 mm Hg) and diastolic (CAPLYTA, -0.83 mm Hg; placebo, -0.29 mm Hg) blood pressure and pulse rate (CAPLYTA, 0.76 bpm; placebo, 0.42 bpm) were minimal and similar between the treatment groups. No patients had treatment-emergent adverse events (TEAEs) related to an increased or a decreased blood pressure.
• A pooled analysis of 3 randomized, double-blind, placebo-controlled trials assessed the safety and tolerability of CAPLYTA 42 mg in the treatment of schizophrenia.⁵ 
  • Minimal changes in mean systolic (-1.1 mm Hg) and diastolic (-0.3 mm Hg) blood pressure were reported with CAPLYTA, and changes were similar to those reported with placebo (systolic, 0.1 mm Hg; diastolic, -0.4 mm Hg).
• A phase 3, randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of CAPLYTA in patients with schizophrenia.⁶ 
  • Orthostatic hypotension was reported in 1 patient in the CAPLYTA 42 mg group and led to treatment discontinuation.
• A 6-week OL study evaluated the safety of CAPLYTA 42 mg in patients with schizophrenia.⁷
  • No changes in multipositional blood pressure, heart rate, or incidence of orthostasis were reported in the study.

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

Earley et al (2025)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 reported in blood pressure were small and not clinically relevant; 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.

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 (CAPLYTA 28 mg, n=176; CAPLYTA 42 mg, n=177; placebo, n=175).³ 

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

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 (CAPLYTA, n=188; placebo, n=189).⁴ 

• Minimal mean changes in blood pressure and pulse rate were reported, and changes were similar between treatment groups; 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.

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 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, and the changes were similar to those reported with placebo; 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 CAPLYTA 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.

• 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 15 September 2025.