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Neuroleptic malignant syndrome in patients with cancer: a systematic review
  1. Izumi Sato1,2,
  2. Hideki Onishi3,
  3. Chiaki Kawanishi4,
  4. Shuhei Yamada5,
  5. Mayumi Ishida3 and
  6. Koji Kawakami1
  1. 1 Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto, Japan
  2. 2 The Keihanshin Consortium for Fostering the Next Generation of Global Leaders in Research (K-CONNEX), Kyoto, Japan
  3. 3 Department of Psycho-Oncology, Saitama Medical University International Medical Center, Hidaka, Saitama, Japan
  4. 4 Department of Neuropsychiatry, Sapporo Medical University Graduate School of Medicine, Sapporo, Hokkaido, Japan
  5. 5 Department of Quality and Patient Safety Management, Chiba Cancer Center, Chiba, Japan
  1. Correspondence to Dr Koji Kawakami, Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University Yoshida Konoecho, Kyoto 606-8501, Japan; kawakami.koji.4e{at}


Background Antipsychotics potentially cause a low incidence of the side effect called neuroleptic malignant syndrome (NMS), which has a high mortality rate. However, few studies on NMS among patients with cancer exist.

Aims We aimed to examine the characteristics of antipsychotic-induced NMS among patients with cancer.

Methods We conducted a systematic review of published reports on NMS described during the treatment of patients with any type of cancer. Articles were identified by a comprehensive search of PubMed, Web of Science, the Cochrane Library and reference lists from relevant articles published until 25 December 2019. Original articles or case reports on humans published in English were included. This review summarises the symptoms, characteristics, treatment course and prognosis of patients with cancer with NMS.

Results Eleven patients with various cancer types from ten case reports published from 1988 to 2013 met the eligibility criteria. Mean age of the 11 patients was 52.5 (range, 32–83) years. NMS developed mostly during the postoperative period, and haloperidol and D2 receptor antagonists were determined as the common causative drugs. Ten patients survived following treatment that mostly involved discontinuing the causative drugs and administering dantrolene, if necessary.

Conclusion Although NMS intrinsically has a low incidence and high mortality, only few reports were available, with most patients surviving after early detection and appropriate treatment. Healthcare providers should consider NMS development while prescribing antipsychotics to ensure prompt recognition of the condition and rapid treatment for preventing unnecessary deaths.

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  • Contributors Titles and abstracts were independently screened by two researchers (IS and HO). If an article could not be judged for eligibility based on the title and abstract, the full-text was screened. Similarly, reference lists from relevant original articles and case reports were screened. Articles were selected by IS and HO. To avoid misclassification bias, our other researchers (HO, CK, SY and MI) checked the data and added variables on clinical aspects, as necessary, after selection of articles by IS and HO. KK supervised all processes of this study.

  • Funding This work was supported by both the Keihanshin Consortium for Fostering the Next Generation of Global Leaders in Research (K-CONNEX), established by Human Resource Development Program for Science and Technology, MEXT, and Grants-in-Aid for Young Scientists (KAKENHI Grant Number 18K15416) from the Japan Society for the Promotion of Science.

  • Competing interests CK reports other from Sumitomo Dainippon Pharma, other from Stella Pharma Corporation, other from CMIC, other from Suntory Beverage & Food, other from Kaken Pharmaceutical, other from Astellas Pharma, other from Mitsubishi Tanabe Pharma Co, other from AbbVie, other from Santen Pharmaceutical, other from Daiichi Sankyo, other from Takeda Pharmaceutical, other from Boehringer Ingelheim Japan, other from School Health Record Centre, other from Real World Data, outside the submitted work.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.