SUMMARY

• The recommended dosage of CAPLYTA is 42 mg once daily. In patients who receive concomitant strong CYP3A4 inhibitors or moderate CYP3A4 inhibitors, the recommended dosage is 10.5 mg once daily or 21 mg once daily, respectively. In special populations such as moderate or severe hepatic impairment, the recommended dosage is 21 mg once daily, which is based on pharmacokinetic data.¹ 
• Lumateperone was studied in doses lower than 42 mg once daily in 2 phase 3 clinical trials in bipolar depression and schizophrenia. The phase 3 clinical trials did not show statistically significant benefit in Montgomery-Åsberg Depression Rating Scale (MADRS) total score and Positive and Negative Syndrome Scale (PANSS) total score, respectively.^2,3 
• A case report of a 24-year-old transgender man with bipolar II disorder and severe persistent asthma who initiated CAPLYTA 42 mg daily but was reduced to CAPLYTA 21 mg daily due to respiratory-related concerns is summarized below.⁴ 

PRODUCT LABELING

Recommended Dosage

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

Dosage Recommendations for Concomitant Use with Moderate or Strong CYP3A4 Inhibitors

The recommended CAPLYTA dosage in patients who receive:¹ 

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

Dosage Recommendations for Patients with Hepatic Impairment

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

CLINICAL DATA

Phase 3 Studies

Use of Lower Dose Adjunctive Lumateperone for Treatment of Bipolar Depression

Suppes et al (2023)² conducted a phase 3, randomized, double-blind, placebo-controlled clinical trial that evaluated the efficacy and safety of lumateperone adjunctive therapy to lithium or valproate in patients with bipolar depression for 6 weeks. Patients were stratified by bipolar I or bipolar II diagnosis and were randomized (1:1:1) to receive lumateperone 28 mg (n=176), CAPLYTA 42 mg (n=177), or placebo (n=176) adjunctive to their ongoing lithium or valproate. The primary efficacy endpoint was change from baseline to day 43 in MADRS total score.

Results

Patients who were treated with adjunctive lumateperone 28 mg saw a least-squares mean difference (LSMD) of -1.7 (95% confidence interval [CI], -3.65 to 0.32, P=0.099) in MADRS total score. The most common treatment emergent adverse events (TEAEs) in the adjunctive lumateperone 28 mg group that occurred in >5% of patients and at more than twice the rate of adjunctive placebo were somnolence (7.4% vs 3.4%) and dizziness (10.2% vs 2.3%).

Use of Lower Dose Lumateperone for Treatment of Schizophrenia

Correll et al (2020)³ conducted a phase 3, randomized, double-blind, placebo-controlled clinical trial that evaluated the efficacy and safety of lumateperone after 4 weeks of treatment in patients experiencing an acute exacerbation of schizophrenia. Patients were randomized (1:1:1) to receive CAPLYTA 42 mg (n=150), lumateperone 28 mg (n=150), or placebo (n=149). The primary efficacy endpoint was the mean change from baseline to day 28 on the PANSS total score versus placebo.

Results

Efficacy was evaluated in the intent-to-treat population, which included 146 patients in the lumateperone 28 mg group and 141 patients in the placebo group. Treatment with lumateperone 28 mg did not show a significant improvement in PANSS total score when compared to placebo. The LSMD was -2.6 (95% CI, -6.2 to 1.1; effect size, -0.2; nominal P=0.16; multiplicity adjusted P=0.18).  

Safety was evaluated based on the safety set, which included 150 patients in the lumateperone 28 mg group and 149 patients in the placebo group. The most common TEAEs occurring in ≥5% of patients in the lumateperone 28 mg arm and more than 2 times the rate in the placebo arm were somnolence (11.3% vs 4%) and fatigue (4.7% vs 1.3%).

Case Report

Pacilio and Dalack (2024)⁴ reported a 24-year-old transgender man with bipolar II disorder and severe persistent asthma. The patient has previously received lurasidone 20 mg daily and cariprazine 1.5 mg sequentially, but discontinued treatment due to difficulty breathing and recurrent dyspnea, respectively. He initiated CAPLYTA 42 mg daily but developed respiratory side effects that he was able to tolerate. During a 6-week follow-up, despite improvement in mood symptoms, his CAPLYTA dose was reduced to 21 mg daily due to respiratory-related concerns. The patient was stabilized on CAPLYTA 21 mg and valproic acid daily and continued to experience mild-moderate respiratory and depressive symptoms. 

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 23 October 2025.