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J R Soc Med. 2004 July; 97(7): 359–360.
PMCID: PMC1079543

Feeling cold after donepezil

We have seen four patients who reported feeling cold within a few weeks of starting donepezil hydrochloride for Alzheimer's disease. On investigation, their temperatures and peripheral circulations were within normal limits. Their Mini Mental State Examination scores at the start of treatment ranged from 13/30 to 22/30 and the medical histories included (1) epilepsy; (2) hypertension, poly-myalgia rheumatica, osteoporosis; (3) transient ischaemic attack, varicose veins, pneumoconiosis; (4) sigmoid diverticular disease, respectively. None had previously reported disturbed temperature perception. Because of this symptom, which began within 8 weeks of starting donepezil, the patients kept their rooms very warm; one patient set the thermostat to 24 °C. Discontinuation of the medication alleviated symptoms in two patients; one died from unrelated causes; and the other decided to tolerate the symptom in view of the benefits derived from donepezil.

A search of Psyclit, Embase, Medline, CINAHL and ACP Journal Club yielded no reports of such a side-effect from donepezil or other cholinergic agents. Nor was it seen in acute pyridostigmine poisoning.1 In healthy volunteers eptastigmine, a new acetylcholinesterase inhibitor, may have a weak effect on (lowering) body temperature.2

Although Alzheimer's disease may involve the suprachiasmatic nucleus of the hypothalamus, and thus potentially affect circadian and bodily temperature rhythms,3 there are no previous reports of changes in self-awareness of temperature in this condition. Temperature disturbances of this sort, although not life-threatening, can be uncomfortable and also costly in extra heating. The possible drug causation deserves systematic assessment. Meanwhile, carers should be particularly sympathetic to patients with Alzheimer's disease when they complain of feeling cold.


1. Almog S, Winkler E, Amitai Y, et al. Acute pyridostigmine overdose: a report of nine cases. Isr J Med Sci 1991;27: 659-63 [PubMed]
2. Mant T, Troetel WM, Imbimbo BP. Maximum tolerated dose and pharmacodynamics of eptastigmine in elderly healthy volunteers. J Clin Pharmacol 1998;38: 610-17 [PubMed]
3. Stopa EG, Volicer L, Kuo-Leblanc V, et al. Pathological evaluation of the human suprachiasmatic nucleus in severe dementia. J Neuropathol Exp Neurol 1999;58: 29-39 [PubMed]

Articles from Journal of the Royal Society of Medicine are provided here courtesy of Royal Society of Medicine Press