[Drug-induced parkinsonian syndromes: a 10-year experience at a regional center of pharmaco-vigilance]

Abstract

Besides classical neuroleptics, several drugs can induce parkinsonian symptoms. The present retrospective study investigates the characteristics of drug-induced parkinsonism notified to the Midi-Pyrénées Pharmacovigilance Centre between 1983 and 1992. Among 3,923 side effects spontaneously reported between 1983 and 1992 to the center, 53 (1.4%) were drug-induced parkinsonism. Mean age was 65 +/- 2 (s.e.m.) years (range 21-88). Drug-induced parkinsonism appeared after a mean treatment duration of 473 +/- 142 days (range 1 day to 15 years) and occurred most frequently in women (63%). The occurrence onset of drug-induced Parkinsonism exhibited a bimodal pattern with a first peak (between 0 and 6 months) mainly due to peripheral or central antidopaminergic drugs and a second one later (between 9 and 12 months) due mostly to calcium channel blockers. Involved drugs were mostly antidopaminergic agents: neuroleptics (antipsychotic drugs: 39%) but also agents used for nausea or vomiting (domperidone, metoclopramide, metopimazine or triethylperazine: 12%) or symptoms associated with menopause (veralipride: 6%). Other cases were related mainly to drugs with "calcium channel blocker" properties (flunarizine and cinnarizine: 30%), H1 antihistamine (1 case), fluoxetine (1 case), alphamethyldopa (1 case) or reserpine (1 case) whereas 3 cases were due to drug interactions. Imputability scores (according to the method of assessment of unexpected drug reactions used in France) were "doubtful" (11%), "plausible" (34%) and "probable" (53%). The complete triad (tremor, akinesia plus rigidity) was seen in 13 (25%) cases. Symmetrical symptoms occurred in 41 (77%) patients. A total disappearance of the clinical feature occurred in 39 (74%) patients whereas in 8 cases (15%), drug-induced parkinsonism led to the diagnosis of underlying idiopathic Parkinson's disease. The present study shows that around 80% of drug-induced parkinsonism are due to two pharmacological classes: central and peripheral antidopaminergic agents and calcium channel blockers.