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Keywords:

  • neuroleptic malignant syndrome;
  • antipsychotics;
  • polypharmacy;
  • individual-matched case–control study

Objective

To investigate the association between neuroleptic malignant syndrome (NMS) and levels of antipsychotic exposure.

Method

Electronic health record data systematically screened from a large mental health service provider in southeast London provided 67 NMS cases which were individually matched with 254 controls on age, gender, and primary psychiatric diagnosis. Data on psychotropic agents, combinations, dose, and dose change of antipsychotic prescriptions over the preceding 5 (oral agents) or 15 days (depot agents) were extracted and compared between groups using conditional logistic regression models.

Results

NMS was associated with higher number of antipsychotic agents used, use of first-generation agents or aripiprazole, use of first-generation agents only or cross-generation agents, and higher mean and maximum daily doses. In further analyses, associations with antipsychotics type remained significant when adjusted for dose, but those with dose were attenuated following adjustment for type. The specific use of haloperidol, aripiprazole, depot flupentixol, and benzodiazepines was independently associated with NMS. Non-white ethnicity was also found to be associated with NMS.

Conclusion

NMS was primarily associated with type of antipsychotic and polypharmacy rather than overall dose. Variation in risk by ethnicity requires further research.