REF-1657 · Hospers et al., 2024 · eClinicalMedicine, · Paper · PubMed

Under heat stress, strongly anticholinergic drugs raised core temperature by 0.42 °C at air temperatures of 30 °C or more and reduced sweating (moderate certainty, atropine only); non-selective beta-blockers (+0.11 °C), adrenaline (+0.41 °C) and anti-Parkinson's agents (+0.13 °C) also raised it, while antidepressants, diuretics and weakly anticholinergic drugs did not, in a meta-analysis of 35 randomised studies of 353 mostly young, healthy people

Main caveat: Mostly young, healthy men (16 F of 353) and short heat exposures; one clinical study.
fairly strong evidenceMeasured on non-athletes to trained athletesRead from the abstract only

Hospers and colleagues tested a warning from public health bodies, including the WHO, that some medications impair thermoregulation, a warning they describe as resting on limited evidence.

They searched MEDLINE, PubMed, Scopus, CINAHL, Web of Science and EMBASE to January 2024 for randomised studies that exposed people to exercise or passive heat while taking a WHO-listed drug or a placebo or no drug, with core temperature (rectal, oesophageal, aural or tympanic) as the main outcome; risk of bias was rated with RoB 2 and certainty with GRADE.

Thirty-five studies with 353 people (16 women) testing 27 drugs were included; average age was under 30, and only one study was in patients. With moderate-certainty evidence, strongly anticholinergic drugs raised core temperature at air temperatures of 30 °C or more by 0.42 °C and reduced sweating, although only atropine had been tested.

Non-selective beta-blockers, adrenaline and anti-Parkinson's agents also raised core temperature. Antidepressants, diuretics and weakly anticholinergic drugs left it unchanged.

The authors conclude that the evidence supports a thermoregulatory penalty for those classes and for no other WHO-listed drug, and that studies of longer exposures, women, older adults and people with chronic disease are needed.

Participants

353 people in 35 studies, 16 of them women (4.5%); average age under 30 across studies.
One study in a clinical population; the rest healthy, by the authors' account mostly young men.
Training status and fitness: not in the abstract.

Methods

Search: MEDLINE, PubMed, Scopus, CINAHL, Web of Science and EMBASE to 30 January 2024; pre-registered in PROSPERO (CRD42020170684).
Inclusion: randomised studies in humans under exertional and/or passive heat stress, testing a drug identified by the WHO against no drug or placebo.
Primary outcome: core temperature (rectal, oesophageal, aural or tympanic).
Quality: Cochrane Risk of Bias 2; certainty by GRADE; only the anticholinergic finding's certainty (moderate) is given in the abstract.

Key Results

Drug classCore temperature vs control (95% CI)Note
Strongly anticholinergic, air temperature ≥30 °C+0.42 °C (0.04 to 0.79); p = 0.03moderate certainty; sweating reduced; atropine only
Non-selective beta-blockers+0.11 °C (0.02 to 0.19); p = 0.02
Adrenaline+0.41 °C (0.21 to 0.61)
Anti-Parkinson's agents+0.13 °C (0.07 to 0.19); p = 0.02
Antidepressantsno change
Diureticsno change
Weakly anticholinergic drugsno change

Practical Application

The drug classes shown to raise core temperature in the heat are strong anticholinergics, non-selective beta-blockers, adrenaline and anti-Parkinson's agents; antidepressants, diuretics and weakly anticholinergic drugs were not. An athlete on one of these has a measured reason to treat hot sessions more cautiously and to tell the prescriber they train or race in the heat (the caution is practice, not tested here).
The average rises were small and the exposures short. 0.11 to 0.42 °C in short heat bouts; how such a rise builds over a long race in the heat is not known from this review.
Inference, not tested here: "no change" for antidepressants and diuretics comes from short exposures in healthy young people; it is not evidence about long-term use, older athletes or people with the conditions these drugs treat.
The prescriber decides. Whether to adjust a dose or change a drug for hot-weather training is the prescriber's decision; the assistant does not change medication and can only suggest the athlete raise heat with the prescriber.
Not settled by this design: drugs not tested, longer heat exposures, women, older or chronically ill athletes, and heat illness or performance as outcomes (core temperature only).

Limitations

Mostly young, healthy men (16 F of 353) and short heat exposures; one clinical study. The authors name women and older adults among the groups barely or not covered.
Core temperature only; no heat illness or performance outcome in the abstract.
The anticholinergic finding rests on atropine alone.
Certainty is given in the abstract only for the anticholinergic finding.
Not all 27 drugs are named in the abstract, so a drug's absence from the table here does not mean it was untested.
Written from the abstract and the PubMed record; full text not read.
How this entry was checked and changed
Why this level

the abstract reports GRADE certainty for its headline finding (moderate, strong anticholinergics at 30 °C or more), which lifts the abstract-only cap (rule 1); 35 studies with 353 people in all are mostly small trials (A-); the certainty of the other findings, including the null results, is not in the abstract

Content correction 2026-11-07
2026-11-07: added from the abstract and the PubMed record; level A- (meta-analysis of mostly small randomised studies; GRADE certainty for the headline reported in the abstract).