Cinnarizine-induced parkinsonism. Susceptibility related to aging and essential tremor

Age at onset in 24 consecutive cinnarizine-induced parkinsonism (CIP) patients referred during a 2-year period was compared with 102 newly referred cases of Parkinson's disease (PD) examined during the same period. Not only did CIP onset occur at a greater age than PD (70.6 + 1.4 years versus 60.1 + 1.1 years), but the number of CIP cases increased steadily with age, whereas the incidence of PD patients peaked between the ages of 55 and 60 years, as is usually the case. At the time of referral, 62% of CIP cases and 14% of PD cases were over the age of 70, suggesting that advanced age was not a source of referral bias. A structured questionnaire prospectively given to 24 CIP patients revealed a history of tremor in at least one family member in 56% of the cases, whereas the incidence was much lower in 124 PD cases (17%) and 102 hospitalized nonneurological patients aged over 65 (6%). Moreover, three of the CIP patients themselves had a history of essential tremor previous to the onset of parkinsonism. CIP patients had frequently been exposed to the drug for years before developing any extrapyramidal symptoms (mean exposure, 4.1 +/- 4 years; range 4 months to 15 years). Though controlled epidemiological studies are needed to evaluate the possibility that cinnarizine is increasingly prescribed in the general population with advancing age, our data suggests that aging plus a background of genetically determined essential tremor represented critical risk factors for development of this drug side effect.