Skip to main content
Full access
Letters
Published Online: 1 July 2012

Donepezil-Induced Mania

Publication: The Journal of Neuropsychiatry and Clinical Neurosciences
To the Editor: The central cholinergic system is believed to play a role in mood disorders, with inhibition of cholinergic activity correlating with mania and facilitation with depression.1 In contrast, six cases of mania related to treatment with donepezil, a centrally-acting acetylcholinesterase inhibitor, have been reported in the literature.24 We report a woman who developed mania after starting donepezil.
“Mrs. W,” a 65-year-old woman with no personal or family history of mental illness, presented with a several day history of insomnia, hyperreligiosity, and agitation. She had a 6- to 12-month history of worsening cognitive dysfunction, personality changes, and functional impairment. Cognitive examination demonstrated recent-memory impairment and executive dysfunction.
Laboratory evaluation, including TSH, MMA, cortisol, RPR, HIV, and serum cryptococcal antigen, was unremarkable. An electroencephalogram was normal. CT and MRI of the brain showed left cerebellar encephalomalacia, white-matter microvascular disease, and lacunar disease in the basal ganglia.
The mania did not resolve with discontinuation of donepezil and treatment with low dose quetiapine, and the patient was transferred to a psychiatric hospital 6 days after admission. She was started on donepezil 5 mg daily for suspected Alzheimer’s disease 5 days before presentation.
The patient had had a cerebellar stroke 8 years earlier and had hypertension, type II diabetes, and hyperlipidemia. She was noncompliant with all medical medications except clopidogrel.
On examination, she acknowledged elevated mood and energy levels. Hypergraphia, pressured speech, and spontaneous singing were noted. Thought examination revealed over-inclusiveness, religious preoccupation, and grandiose delusions.
The six patients reported previously who developed mania with donepezil ranged in age from 50 to 78. Four were women; five carried diagnoses of dementia; and one had cognitive impairment related to a cerebral aneurysm and repair. Two patients had histories of bipolar I disorder, and two had depression. Four were on other medications that can cause mania (antidepressants, carbidopa/levodopa). Mania developed in most patients within 1 week of donepezil initiation, and resolved in most within 1 week of discontinuation. Our patient resembled previous reported cases wherein she was elderly, had vascular dementia, and developed mania within days of starting donepezil. It is unclear how donepezil may induce mania; one possibility is an increase in acetylcholine leading to changes in norepinephrine, dopamine, serotonin, or other neurotransmitters.5 Our case and those previously reported suggest that donepezil could precipitate mania in the context of cerebrovascular or other brain diseases, mood disorders, and/or treatment with other medications that can cause mania.

References

1.
Janowsky DS, el-Yousef MK, Davis JM, et al.: A cholinergic-adrenergic hypothesis of mania and depression. Lancet 1972; 2:632–635
2.
Benazzi F: Mania associated with donepezil. J Psychiatry Neurosci 1999; 24:468–469
3.
Collins C, Copeland B, Croucher M: Bipolar affective disorder, type II, apparently precipitated by donepezil. Int Psychogeriatr 2011; 23:503–504
4.
Rao V, Ovitt L, Robbins B: Donepezil induced hypomania. J Neuropsychiatry Clin Neurosci 2008; 20:107
5.
Decker MW, McGaugh JL: The role of interactions between the cholinergic system and other neuromodulatory systems in learning and memory. Synapse 1991; 7:151–168

Information & Authors

Information

Published In

Go to The Journal of Neuropsychiatry and Clinical Neurosciences
Go to The Journal of Neuropsychiatry and Clinical Neurosciences
The Journal of Neuropsychiatry and Clinical Neurosciences
Pages: E27
PubMed: 23037669

History

Published online: 1 July 2012
Published in print: Summer 2012

Authors

Details

Sarah Wicklund, M.D.
Department of Psychiatry, Medical College of Wisconsin, Milwaukee, WI
Mark Wright, M.D.
Department of Psychiatry, Medical College of Wisconsin, Milwaukee, WI

Competing Interests

 The Authors report no conflicting financial relationships.

Metrics & Citations

Metrics

Citations

Export Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download.

For more information or tips please see 'Downloading to a citation manager' in the Help menu.

Format
Citation style
Style
Copy to clipboard

View Options

View options

PDF/EPUB

View PDF/EPUB

Get Access

Login options

Already a subscriber? Access your subscription through your login credentials or your institution for full access to this article.

Personal login Institutional Login Open Athens login
Purchase Options

Purchase this article to access the full text.

PPV Articles - Journal of Neuropsychiatry and Clinical Neurosciences

PPV Articles - Journal of Neuropsychiatry and Clinical Neurosciences

Not a subscriber?

Subscribe Now / Learn More

PsychiatryOnline subscription options offer access to the DSM-5-TR® library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development.

Need more help? PsychiatryOnline Customer Service may be reached by emailing [email protected] or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.).

Media

Figures

Other

Tables

Share

Share

Share article link

Share