Objective: To describe the case of a patient who developed severe multifocal myoclonus due to donepezil.

Background: Donepezil is a cholinesterase inhibitor frequently used to treat dementia [1]. Most common side effects include gastrointestinal symptoms, muscle cramps or sleep problems [2]. More serious side effects include seizures, urinary retention or bradycardia [1]. Movement disorders are exceedingly rarely associated with its use [3]. On the contrary, donepezil has actually been studied as a treatment option for tardive dyskinesias [4].

Method: This is a 67-year-old man with a past medical history of medullary and occipital strokes, hypertension, diabetes mellitus type 1, hepatitis C who presented with progressive involuntary movements described as “tremors”. He reported sudden onset abdominal twitching which rapidly evolved into severe abnormal movements of the upper body. On exam, he had multifocal myoclonic movements of his head, face, upper extremities and trunk which were severe enough to prevent him from sitting up, sleeping and eating. The only recent change in his life style/medication regimen was the initiation of donepezil 4 weeks prior.

Results: MRI of the brain with and without contrast did not show any acute intracranial pathology. Comprehensive  metabolic work up, including thyroid stimulating hormone was unrevealing. Donepezil was held and he was started on clonazepam 0.5mg nightly for 7 days. The myoclonic movements subsided within one day and had not recurred when he followed up in clinic 4 months later.

Conclusion: Our patient suffered from severe myoclonic movements which were most likely caused by donepezil. Five other cases of myoclonus caused by centrally acting (Donepezil [5,6] and Tacrin [7]) or peripherally active cholinesterase inhibitors (physostigmine [8]) have been reported thus far in the literature. The exact mechanism by which the medication can cause myoclonus is unclear but seems to be related to its primary cholinergic mechanism. Interestingly, both hypercholinergic [9,10] as well as hypocholinergic [11,12] central drug effects have been associated with causation or amplification of myoclonus raising the question of a rather modulatory effect of the central cholinergic system on myoclonic movement disorders. Given its common use and the general perception that cholinesterase inhibitors are relatively safe, medical professionals should be aware of potential and infrequent adverse reactions such as observed in this case.

References: 1) Seltzer, Ben. “Donepezil: an update.” Expert opinion on pharmacotherapy 8.7 (2007): 1011-1023. 2) Shigeta, Masahiro, and Akira Homma. “Donepezil for Alzheimer’s disease: pharmacodynamic, pharmacokinetic, and clinical profiles.” CNS Drug Reviews 7.4 (2001): 353-368. 3) Cacabelos, Ramón. “Donepezil in Alzheimer’s disease: from conventional trials to pharmacogenetics.” Neuropsychiatric Disease and Treatment 3.3 (2007): 303. 4) Bergman, Joseph, et al. “Beneficial effect of donepezil in the treatment of elderly patients with tardive movement disorders.” The Journal of clinical psychiatry 66.1 (2005): 107-110. 5) Bougea, Anastasia, et al. “Donepezil-induced myoclonus in a patient with Alzheimer disease.” Annals of Pharmacotherapy 48.12 (2014): 1659-1661. 6) Whateley, Jennifer M., Alice J. Huffman, and Emily J. Henderson. “Acute inability to mobilise resulting from probable donepezil-induced myoclonus.” Age and ageing 47.6 (2018): 907-908. 7) Abilleira, S., M. VIGUERA, and F. Miquel. “Myoclonus induced by tacrine.” Journal of neurology, neurosurgery, and psychiatry 64.2 (1998): 281. 8) Mayeux, Richard, Marilyn Albert, and Michael Jenike. “Physostigmine‐induced myoclonus in Alzheimer’s disease.” Neurology 37.2 (1987): 345-345. 9) Chokroverty, Sudhansu, Mahendra K. Manocha, and Roger C. Duvoisin. “A physiologic and pharmacologic study in anticholinergic‐responsive essential myoclonus.” Neurology 37.4 (1987): 608-608. 10) Rektor, Ivan, et al. “Influence of cholinergic system on myoclonus in myoclonic epilepsies.” Movement disorders: official journal of the Movement Disorder Society 7.3 (1992): 224-227. 11) Moos, Daniel D. “Central anticholinergic syndrome: a case report.” Journal of PeriAnesthesia Nursing 22.5 (2007): 309-321. 12) Holinger, P. C., and H. L. Klawans. “Reversal of tricyclic-overdosage-induced central anticholinergic syndrome by physostigmine.” The American journal of psychiatry 133.9 (1976): 1018-1023.

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