Risk of Neuroleptic malignant syndrome among patients exposed to antipsychotics

Abstract

Background: Neuroleptic malignant syndrome (NMS), a rare but serious adverse reaction of antipsychotics. However, little evidence of risk and epidemiology of NMS is available. Aim: To determine the risk of NMS associated with haloperidol, olanzapine, quetiapine, and risperidone. To characterise the incidence and case fatality risk of NMS in antipsychotic users. Methods: We conducted a population-based cohort analysing health records of 297 647 antipsychotic users and measure the incidence and case fatality risk of NMS. We estimated the risk of NMS associated with exposure to antipsychotics, by comparing the exposure status during day 1-30, and day 91-120 preceding the diagnosis of NMS. Results: After adjustment for time trends in exposure, concurrent medications, and medical conditions, diagnosis of NMS was associated with exposure to haloperidol (OR, 4.40; 95% Cl 1.97-9.81), and quetiapine (OR, 4.32; 95% Cl, 1.70-10.97). There was no observed association for risperidone (OR, 2.00; 95% Cl, 0.93-4.32) or olanzapine (OR, 1.23; 95% Cl, 0.47-3.18). NMS occurred with an incidence of 1.10 per 1000 persons. The case fatality risk of NMS was measured as 6.0%. Conclusions: Patients had increased odds of exposure to, haloperidol and quetiapine but not risperidone or olanzapine, during the 30 days prior to the diagnosis of NMS, as compared with the earlier reference period. Clinicians who prescribe antipsychotics should weigh the acutely increased risk of NMS with the potential benefits of antipsychotic therapy, especially for haloperidol and quetiapine.