Lumateperone, a treatment for schizophrenia, may have an underestimated safety profile, necessitating careful monitoring, particularly in women and individuals with bipolar II disorder, according to a recent study. The research, led by Yanjing Zhang from the First Hospital of Hebei Medical University, analyzed data from the FDA Adverse Event Reporting System (FAERS) to evaluate the safety properties of lumateperone and provide evidence-based guidance for its clinical use.
FAERS Data Analysis
The investigators analyzed adverse event (AE) reports in FAERS from the fourth quarter of 2019 to the first quarter of 2024. They assessed disproportionality in lumateperone-associated AEs using various measures, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). Logistic regression analyses were also conducted to identify risk factors for severe AEs.
The analysis included 2,644 AE reports where lumateperone was the primary suspected drug, with 739 classified as severe AEs and 1905 as non-severe. The study identified 130 preferred terms (PTs) with significant disproportionality, with 67 (51.53%) not included in the product labeling, affecting 6 systems and organs. Dizziness was the most reported severe AE (n = 81), and tardive dyskinesia showed the strongest signal (ROR = 186.24).
Risk Factors Identified
Logistic regression analysis revealed that female gender (OR, 1.811 [95% CI, 1.302-2.519]; P = .000), bipolar II disorder (OR, 1.695 [95% CI, 1.320-2.178]; P = .000), and concomitant drug use were independent risk factors for lumateperone-associated severe AEs. Conversely, concomitant use of CYP3A4 inhibitors or drugs metabolized by CYP3A4 was associated with a decreased risk of severe AEs (OR, 0.524 [95% CI, 0.434-0.633]; P = .000).
Clinical Implications
"These results underscore the need for healthcare providers to exercise heightened caution when prescribing lumateperone and to inform patients about these potential AEs," Zhang and colleagues concluded. The study highlights the importance of considering individual patient risk factors and potential drug interactions when prescribing lumateperone to minimize the risk of severe adverse events. Further research and safety assessments are warranted to validate these findings and refine clinical guidelines.
