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Can J Psychiatry. 2012 Aug;57(8):512-8.

Neuroleptic malignant syndrome-an 11-year longitudinal case-control study.

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  • 1Unit for Psychiatric Research, Aalborg Psychiatric Hospital, Aarhus University Hospital, Aalborg, Denmark.



To describe patients with neuroleptic malignant syndrome (NMS), to establish occurrence of NMS, to investigate risk factors of NMS, and to investigate mortality associated with NMS.


We conducted a longitudinal register linkage case-control study of NMS.


In health care registers covering the period from 1996 to 2007, we identified, among 224 372 patients with organic, psychotic, affective, or neurotic diagnosis, 83 patients with NMS, equivalent to an occurrence of 0.04%. Treatment with second-generation antipsychotics (SGAs) in the 3 months preceding admission increased the NMS risk (OR 4.66; 95% CI 1.96 to 11.10) and also first-generation antipsychotics (FGAs) of high potency (OR 23.41; 95% CI 5.29 to 103.61) and mid potency (OR 4.81; 95% CI 1.96 to 11.79), and depot antipsychotics (OR 4.53; 95% CI 1.60 to 12.80). Benzodiazepines (BDZs) also increased the risk of NMS (OR 3.43; 95% CI 1.68 to 12.80). NMS was associated with an increased mortality (HR 1.88; 95% CI 1.19 to 2.98) in patients, compared with sex-, age-, and diagnosis-matched control subjects, but no significant difference in mortality between patients and control subjects was observed after the initial 30 days (P = 0.27).


The occurrence of NMS is low, and the prediction of NMS is difficult. Previous treatment with FGAs, SGAs, and BDZs was identified as a risk factor for developing NMS. NMS increased mortality within 30 days after NMS.

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