Objective:Donepezil(Aricept) appears to be a very safe medication when used in selected patients with mild to moderate Alzheimer's disease. Nightmares are reported complication of aricept therapy and treated easily by administrating the dose in the morning. We experienced 1 case of nightmare which was treated not by administrating schedule change but by reducing the dose, and recurred by co-administration of mirtazapine(remeron).
Case:84-year-old male patient was presented with 2-year history of cognitive impairmen. He had a MMSE score of 22/30. After a complete dementia workup, he was diagnosed with Alzheimer's disease using the DSM-IV criteria, and he was prescribed 5mg of aricept to be given in the morning. After 4 weeks, he feels better, but his cognitive function was not improved. The dose of donepezil was increased to 10mg. 2 weeks later, in routine follow-up he complained of many unpleasant dreams. The dose of donepezil was reduced to 5mg. His dreams were reduced, and the content of dreams were similar to his previous healthy state. 4 months later, He complained of dysphoria and insomnia, and antidepressant therapy was started with remeron 30mg orally every night. After 1 month, he again complained of many unpleasant dreams and the dose of remeron was reduced 15mg. 1 month later, he continued to complain of unpleasant dreams, remeron was discontinued. After 2 months, although there was no obvious cognitive improvement on the medication, his global function became better, and his son and daughter-in-law were satisfied with his state.
Discussion:Like other dreams, nightmares almost always occurs during REM sleep and usually after a long REM period late in the night. There is a convergent data suggesting the involvement of brain stem cholinergic neurons in the regulation of REM sleep, and acetylcholinestrase inhibitors decrease REM latency and increase REM density. According to these data, the mechanism of nightmare might be cholinergic enhancement in the brain. In this case, nightmares may be related to the plasma level of aricept. 1)Unpleasant dreams were appeared in the 10mg of aricept and disappeared when the dose of aricept was reduced to 5mg 2)They were reappeared co-administration of remeron and disappeared when remeron was stopped. Aricept is highly protein-bound and metabolized by the liver via the cytochrome P450 2D6 and 3A4 isoenzyme. Inhibition of cytochrome P450 system may lead to elevated plasma levels of co-administered drugs that metabolized by this enzyme. An elevated plasma level of aricept may in turn increase the risk for more adverse reactions.
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