Parkinsonism onset in a patient concurrently using tiapride and donepezil.

Donepezil was approved by the U. S. Food and Drug Administration in November 1 996 for treating patients with mild-to-moderate Alzheimer's disease. The use of donepezil has been associated with the worsening of (1, 2) and occurrence of parkinsonism (3). In 1999, donepezil was approved for use in Japan. The instructions for physicians, however, do not describe this potential adverse effect. The occurrence of severe parkinsonism in a patient concurrently using tiapride and donepezil is reported. A 79-year-old womanwith a history of visual hallucinations and mild dementia visited a psychiatrist. She and her family members denied that she had had difficulty in walking. No medications had been previously prescribed. She was prescribed 25 mgof tiapride once daily. The dose was increased to 25 mg twice daily 2 weeks later; her visual hallucinations disappeared. Four weeks after starting tiapride, she was prescribed 3 mgof donepezil once daily to alleviate the cognitive symptoms. Twoweeks later, the dose was increased to 5 mgonce daily, and one weekafter that, she started to walk with a stoop and required assistance. Therefore, she was referred to our clinic. She was afebrile, her face was expressionless, and she spoke in a low voice. Her cranial nerve functions were intact. She was unable to stand or walk unaided. She had a marked stooped posture while standing or sitting on a stool. Barre arm and leg signs were negative. All four limbs showedsevere bradykinesia and mild plastic rigidity; there was no obvious laterality. She had no tremor at rest or during action. Ankle jerks were hypoactive on both sides, but other tendon reflexes were normal. Sensation was intact. A neck X-ray showed no narrow canal. Cranial MRimages demonstrated multiple small infarcts in the thalamus, basal ganglia, and cerebral white matter on both sides, suggesting a diagnosis of multi-infarct dementia. However, there was no fresh infarct. Both tiapride and donepezil were discontinued. On the following day, her gait disturbance began to improve. In ten days, she could walk without assistance and the rigidity had disappeared. Because the temporal relationship between the ingestion of donepezil and the occurrence of parkinsonism was so noticeable, it is highly likely that donepezil in combinationwith tiapride caused the severe parkinsonism. Donepezil enhances central cholinergic activity by inhibiting acetylcholinesterase in the brain. Thus, the use of donepezil and dopamine D2blockers must have caused the acetylcholine/dopamine imbalance in the striatum, producing parkinsonism (4). Clinicians should be aware of this possible interaction when dopamine-blocking drugs are used with donepezil.