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Drug-associated non-pyrogenic hyperthermia: a narrative review

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Hyperthermia occurs when heat accumulation surpasses the body’s ability for heat dissipation. Many drugs may affect thermoregulation. This narrative review aimed to provide an overview of the current literature concerning reports of drug-associated non-pyrogenic hyperthermia.


A comprehensive search was performed across 5 databases covering the period of inception to March 2019, for publications that reported hyperthermia associated with drug use. Studies that reported potential drug association with hyperthermia due to altered thermoregulatory mechanisms were included. Case reports of less than 3 cases were excluded, as well as hyperthermia due to other causes, such as hypersensitivity, malignant hyperthermia and neuroleptic malignant syndrome. The primary outcomes of interest were hospitalisation and mortality.


The literature search initially identified a total of 2609 records. Based on full-text analysis, 11 articles met the inclusion criteria, of which there were 5 case-control studies, 2 case series and 4 retrospective analyses. Studies reported heat-related hospitalisations or emergency department presentations associated with the use of psychotropics (antipsychotics, antidepressants and anxiolytics), anticholinergics, antihistamines, diuretics, cardiovascular agents, non-steroidal anti-inflammatory drugs and anticoagulants. Psychotropic drugs were reported to be associated with increased heat-related mortality, other than through neuroleptic malignant syndrome, but findings varied among the studies.


Given the relative lack of publications, more research is necessary to study specific effects of drugs on body temperature and the likelihood of inducing non-pyrogenic hyperthermia. In particular, psychotropics, anticholinergics, diuretics and cardiovascular agents are of interest for future studies.

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Authors and Affiliations



KSB, MSS and GMP designed the project, reviewed publications and wrote the manuscript. KSB performed the literature searches.

Corresponding author

Correspondence to Gregory M. Peterson.

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The authors declare that they have no conflicts of interest.

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Key points

• With the expected increasing global temperatures in the coming decades, heat-related mortality will rise. Identification of possible factors which can contribute to hyperthermia, including specific drug use, is of utmost importance.

• This review found that drugs reportedly associated with non-pyrogenic hyperthermia varied, with the primary groups being psychotropics, anticholinergics, diuretics and cardiovascular drugs.

• More research is necessary to identify the mechanisms, risk factors and incidence of drug-associated hyperthermia.

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Bongers, K.S., Salahudeen, M.S. & Peterson, G.M. Drug-associated non-pyrogenic hyperthermia: a narrative review. Eur J Clin Pharmacol 76, 9–16 (2020).

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