Donepezil-Induced Myoclonus in a Patient With Alzheimer Disease

Objective: To report an uncommon adverse event in an elderly patient related to the cholinesterase inhibitor, donepezil. Case Summary: An 80-year-old Greek woman with Alzheimer disease was admitted to the hospital with a sudden onset of myoclonus in both upper and lower extremities after receiving 30 mg of donepezil daily for 25 days. After 36 hours of donepezil remission, the frequency of the myoclonic jerks was sharply reduced. The patient remains asymptomatic after 6 months of follow-up. Discussion: Our literature search yielded only 2 cases of myoclonus in relation to memantine, which has a different action with donepezil; to our knowledge, this is the first report of generalized myoclonus induced by donepezil overdosing. Based on the Naranjo probability scale it was probable that the patient’s myoclonus was related to donepezil because of clear temporal proximity and lack of alternative explanations. Conclusions: Clinicians should take into consideration therapeutic drug monitoring in the event of a potentially rare serious adverse reaction. Further studies are needed to clarify the possible role of donepezil in the pathophysiology of myoclonus.

[1]  M. Hashimoto,et al.  Efficacy of increasing donepezil in mild to moderate Alzheimer's disease patients who show a diminished response to 5 mg donepezil: a preliminary study , 2013, Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society.

[2]  A. Verkhratsky,et al.  The serotonergic system in ageing and Alzheimer's disease , 2012, Progress in Neurobiology.

[3]  D. Moellentin,et al.  Memantine-Induced Myoclonus and Delirium Exacerbated by Trimethoprim , 2008, The Annals of pharmacotherapy.

[4]  S. Papageorgiou,et al.  Exacerbation of myoclonus by memantine in a patient with Alzheimer disease. , 2007, Journal of clinical psychopharmacology.

[5]  A. Lajtha,et al.  Changes in cerebral neurotransmitters and metabolites induced by acute donepezil and memantine administrations: A microdialysis study , 2006, Brain Research Bulletin.

[6]  B Müller-Oerlinghausen,et al.  The AGNP-TDM Expert Group Consensus Guidelines: Therapeutic Drug Monitoring in Psychiatry , 2004, Pharmacopsychiatry.

[7]  J. Caviness Myoclonus and neurodegenerative disease--what's in a name? , 2003, Parkinsonism & related disorders.

[8]  S. Tsuji,et al.  Amantadine-induced cortical myoclonus , 2001, Neurology.

[9]  R. Edwards,et al.  Donepezil Overdose: A Tenfold Dosing Error , 1999, The Annals of pharmacotherapy.

[10]  R. Mohs,et al.  Donepezil improves cognition and global function in Alzheimer disease: a 15-week, double-blind, placebo-controlled study. Donepezil Study Group. , 1998, Archives of internal medicine.

[11]  S H Ferris,et al.  Diagnosis and treatment of Alzheimer disease and related disorders. Consensus statement of the American Association for Geriatric Psychiatry, the Alzheimer's Association, and the American Geriatrics Society. , 1997, JAMA.

[12]  D. Geldmacher Donepezil (Aricept) therapy for Alzheimer's disease. , 1997, Comprehensive therapy.

[13]  D. Morgan The dopamine and serotonin systems during aging in human and rodent brain. A brief review , 1987, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[14]  Y. Ugawa,et al.  Myoclonus in Alzheimer's disease , 1987, Journal of Neurology.

[15]  D. Greenblatt,et al.  A method for estimating the probability of adverse drug reactions , 1981, Clinical pharmacology and therapeutics.

[16]  Jin-Tai Yu,et al.  Efficacy and safety of donepezil, galantamine, rivastigmine, and memantine for the treatment of Alzheimer's disease: a systematic review and meta-analysis. , 2014, Journal of Alzheimer's disease : JAD.

[17]  F. Jiménez-Jiménez,et al.  Drug-Induced Myoclonus , 2004, CNS drugs.

[18]  Donepezil (Aricept) for Alzheimer's disease. , 1997, The Medical letter on drugs and therapeutics.