Evaluation of neuroleptic malignant syndrome induced by antipsychotic drugs using spontaneous reporting system
Sakiko Hirofuji,
Koumi Miyasaka,
Mika Maezawa,
Wataru Wakabayashi,
Keita Oura,
Satoshi Nakao,
Nanaka Ichihara,
Yuka Nokura,
Moe Yamashita,
Kensuke Matsui,
Hideyuki Tanaka,
Mayuko Masuta,
Ichiro Ieiri,
Kazuhiro Iguchi,
Mitsuhiro Nakamura
Affiliations
Sakiko Hirofuji
Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4, Daigaku-nishi, Gifu, 501-1196, Japan
Koumi Miyasaka
Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4, Daigaku-nishi, Gifu, 501-1196, Japan
Mika Maezawa
Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4, Daigaku-nishi, Gifu, 501-1196, Japan
Wataru Wakabayashi
Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4, Daigaku-nishi, Gifu, 501-1196, Japan
Keita Oura
Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4, Daigaku-nishi, Gifu, 501-1196, Japan
Satoshi Nakao
Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4, Daigaku-nishi, Gifu, 501-1196, Japan; Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
Nanaka Ichihara
Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4, Daigaku-nishi, Gifu, 501-1196, Japan
Yuka Nokura
Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4, Daigaku-nishi, Gifu, 501-1196, Japan
Moe Yamashita
Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4, Daigaku-nishi, Gifu, 501-1196, Japan
Kensuke Matsui
Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4, Daigaku-nishi, Gifu, 501-1196, Japan
Hideyuki Tanaka
Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4, Daigaku-nishi, Gifu, 501-1196, Japan
Mayuko Masuta
Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4, Daigaku-nishi, Gifu, 501-1196, Japan
Ichiro Ieiri
Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
Kazuhiro Iguchi
Laboratory of Community Pharmacy, Gifu Pharmaceutical University, 1-25-4, Daigaku-nishi, Gifu, 501-1196, Japan
Mitsuhiro Nakamura
Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4, Daigaku-nishi, Gifu, 501-1196, Japan; Corresponding author.
Adverse events (AEs) of antipsychotic drugs include neuroleptic malignant syndrome (NMS), which presents complex clinical symptoms, resulting in a fatal outcome. In this study, the association between antipsychotic drugs and NMS was comprehensively evaluated by cluster and association analyses using the Japanese Adverse Drug Event Report (JADER) database.The analyses were performed using 20 typical antipsychotics (TAPs) alongside 9 atypical antipsychotics (AAPs). The Standardised MedDRA Queries (SMQ) database was used to analyze NMS (SMQ code: 20000044). Reporting odds ratios (RORs) were used for AE signal detection. The relationship between antipsychotic drugs and AEs for NMS was investigated by performing hierarchical cluster analysis using Ward's method.Between April 2004 and September 2021, the total number of JADER reports was 705,294. RORs (95 % confidence interval) of NMS for haloperidol, chlorpromazine, risperidone, and aripiprazole were 12.1 (11.1–13.3), 6.3 (5.7–7.0), 6.2 (5.8–6.6), and 4.7 (4.4–5.1), respectively. Three clusters were formed, with characteristics as follows: Cluster 1 consisted of only TAPs, such as bromperidol and fluphenazine, whilst having a high reporting rate of hypotension, tachycardia, dyskinesia, and dystonia. Cluster 2 consisted of all AAPs alongside several TAPs, such as haloperidol and chlorpromazine, with higher reporting rates of disturbance of consciousness, extrapyramidal disorders (excluding dyskinesia and dystonia), and serotonin syndrome. Cluster 3 consisted of only perphenazine, whilst having a higher reporting rate of coma, leukocytosis, and Parkinsonism.The results of this study may therefore aid in the management of NMS using antipsychotic drugs.
