Extrapyramidal side‐effect due to drug combination of risperidone and donepezil

Abstract

Behavioral and psychological symptoms of dementia (BPSD) are common in Alzheimer's disease (AD). Antipsychotics are usually used to treat the BPSD in the pharmacological approach. New generation atypical antipsychotics are shown to have a lower incidence of extrapyramidal side-effects (EPS) and are the drug of choice in treating geriatric psychiatric patients.1, 2 On the other hand, cognitive symptoms of AD patients are usually treated with cholinesterase inhibitors such as donepezil and rivastigmine. Concomitant use of antipsychotics and cholinesterase inhibitors is therefore very common in elderly dementia patients. The drug interaction between these two classes of drugs should be evaluated carefully. Ms A, an 80-year-old woman, had been suffering from AD for 4 years. She was admitted to geriatric ward of Taipei City Psychiatric Center due to cognitive impairment and psychiatric symptoms of psychosis and aggression. Donepezil 5 mg/day was prescribed for her cognitive dysfunction and risperidone 1 mg/day was added 12 days after. Adverse effects including general weakness and vomiting were noted on the second day after the addition of risperidone and rapid increased generalized rigidity was noted thereafter. She became almost immobilized after three doses of risperidone, after which it was discontinued. Parkinsonian features improved spontaneously in 1 week. However, her psychiatric disturbances were aggravated again so olanzapine 2.5 mg/day was added. Her psychiatric symptoms responded relatively well to olanzapine and there was no more parkinsonian features in follow-up period up to now. The combination of risperidone and donepezil has been reported to result in severe EPS.3 However, the side-effects in Magnuson et al.'s case appeared gradually after at least of 8 weeks of risperidone treatment and including 6 weeks of donepezil combination. The interesting finding in the present case was that the patient developed severe EPS abruptly after 3 days of risperidone 1 mg/day with pre-existing 12 days of donepezil 5 mg/day. Donepezil acts to increase the acetylcholine (ACh) level. The balance between ACh and dopamine in the striatum is important in controlling the extrapyramidal symptoms. Therefore, the increased ACh might lead to the imbalance between ACh and dopamine and then increase the susceptibility to dopamine blockade. However, the susceptibilities to parkinsonism were different between risperidone and olanzapine in the present case. This could be due to higher D2 blockade in risperidone than in olanzapine.4 Further clinical observations of more drug combinations in AD patients are necessary in confirm the speculation.