SUMMARY

• There were no reports of serotonin syndrome adverse events in CAPLYTA clinical trials across all indications (adjunctive major depressive disorder [MDD], bipolar I or II disorder, and schizophrenia).
• In an analysis of postmarketing safety data from the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database from the fourth quarter of 2019 to the fourth quarter of 2023, 12 cases of serotonin syndrome were reported.¹ 

PRODUCT LABELING

Clinically Important Drug Interactions with CAPLYTA

Increased monitoring for serotonin reuptake inhibitors (SRI)-associated adverse reactions is recommended.² 

Although no clinically significant drug interactions with adjunctive selective serotonin reuptake inhibitors/serotonin norepinephrine reuptake inhibitors (SSRI/SNRIs) in MDD were observed in CAPLYTA clinical trials, CAPLYTA’s moderate serotonin transporter (SERT) activity may increase the risk of SRI-associated adverse reactions (e.g. serotonin syndrome, hyponatremia).² 

clinical data

There were no reports of serotonin syndrome adverse events in CAPLYTA clinical trials across all indications (adjunctive major depressive disorder, bipolar I or II disorder, and schizophrenia).

postmarketing safety data

FDA Adverse Event Reporting System

Sun et al (2025)​¹ conducted an analysis using the FAERS database (first quarter of 2019 to the fourth quarter of 2023) to evaluate the effects of CAPLYTA in schizophrenia patients on the nervous system. Of the 1762 lumateperone-related adverse events, 12 cases of serotonin syndrome reported (reporting odds ratio [ROR] 8.87, 95% confidence interval [CI, 5.03-15.64]).

FAERS is a voluntary reporting system that has certain limitations, and not all adverse events related to CAPLYTA will be reported to the FDA. Relying solely on FAERS data cannot determine a causal relationship between drug use and adverse events.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 28 October 2025.