Investigation into neuroleptic malignant syndrome triggered by atypical antipsychotics: Insights from FDA adverse event reporting system database

Abstract

Objective: Neuroleptic malignant syndrome (NMS) is a rare but potentially life-threatening reaction associated with dopamine antagonists, particularly typical antipsychotics. Despite the relatively low incidence of NMS linked to atypical antipsychotics (AAPs), there is a notable lack of extensive real-world studies investigating this condition.

Methods: This study utilizes data from the FDA Adverse Event Reporting System (FAERS) from 2004 to 2024, employing disproportionality analysis to explore the association between fourteen commonly prescribed AAPs and NMS. Multivariate logistic regression was conducted to identify risk factors for mortality related to NMS.

Results: We analyzed 79,980 primary suspected adverse drug event (ADE) reports for NMS, revealing a slight male predominance and a median age of 48 years (Interquartile Range [IQR]: 31-64). Patients were primarily located in Europe and the United States. Ziprasidone exhibited the strongest pharmacovigilance signal (Reporting Odds Ratio [ROR] = 3.09; 95 % confidence interval [CI]: 2.97-3.21), while lurasidone showed the lowest signal strength (ROR = 1.58; 95 % CI: 1.52-1.65). The median time to onset of NMS was 42 days (IQR: 9-328.25). Significant mortality risk factors included age ≥ 65 years (Odds Ratio [OR] = 4.45; 95 % CI: 3.33-5.95), Parkinson's disease (OR = 32.69; 95 % CI: 14.75-72.46), and malignant hyperthermia (OR = 25.23; 95 % CI: 8.62-73.83), with an area under the curve (AUC) of 0.877.

Conclusion: This study provides vital pharmacovigilance insights regarding NMS related to AAPs, enhancing the understanding of its clinical implications.

Keywords: Adverse drug events; Atypical antipsychotic; FAERS; Neuroleptic malignant syndrome.