Is donepezil useful for improving cognitive dysfunction in bipolar disorder?

Background
Cognitive dysfunctions are being recognized as a major roadblock to functional recovery in patients with bipolar disorders. Little is known about the treatment of these cognitive dysfunctions. Donepezil, approved to treat memory dysfunction in Alzheimer’s disease, is evaluated for cognitive dysfunctions common in bipolar disorder. Of concern is some evidence that donepezil may trigger affective instability.

Methods
All bipolar disordered patients in a private practice setting treated with donepezil for memory problems were analyzed. Patients were assessed for memory improvement and change in psychiatric status with the Clinical Global Impression of Improvement Scale.

Results
Thirty-nine of 58 patients (67%) reported improvement with a mean score of 1.82 (standard deviation ± 0.82). Nine treatments were stopped because of side effects and 4 showed no response. No bipolar I patient received benefits. Thirty-six of 43 (84%) of bipolar II patients showed improvement. Fifty percent of bipolar NOS showed improvement. Four bipolar I patients (57%), 1 bipolar II patient (2%) and 2 bipolar NOS patients (25%) stopped donepezil due to worsening affective symptoms.

Limitations
This is a naturalistic case series with a single evaluator. Other medications used in treatment were changed as clinically indicated.

Conclusions
This case series suggests utility for donepezil in the treatment of cognitive problems associated with bipolar II disorder and bipolar disorder NOS. Bipolar I patients showed no improvement and a concerning trend to destabilize with donepezil treatment.

Keywords: Donepezil; Cholinesterase inhibitor; Bipolar I; Bipolar II; Cognitive dysfunction; Memory

Tammas Kelly
503 Remington St., Fort Collins, Colorado 80524, United States
Received 20 April 2007;  revised 26 July 2007;  accepted 31 July 2007.  Available online 10 September 2007.

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