Drugs Associated With Restless Legs Syndrome A Case/Noncase Study in the French Pharmacovigilance Database

Background: Several case reports have suggested that drugs could induce restless legs syndrome. However, no systematic review of this adverse drug reaction (ADR) in a pharmacovigilance database has been published. Objective: To assess the frequency of restless legs syndrome in the French Pharmacovigilance Database. Methods: We selected all ADR reports from January 1, 1984 to December 31, 2009 coded as restless legs syndrome. Restless legs syndrome diagnosis was validated from case descriptions. Using a case/noncase approach, reporting odds ratio and 95% confidence interval were calculated for "suspected" drugs with 2 or more observations. Results: Twenty-six ADR reports were found. Four cases were excluded because of alternative diagnosis. Fourteen cases were women (64%). Median age was 57. Most frequently suspected drugs were antidepressants (reporting odds ratio, 15.9 [6.4-39.7]; amitriptyline, escitalopram, mianserine, mirtazapine, duloxetine), neuroleptics (17.8 [6.1-51.7]; thioridazine, loxapine, risperidone, aripiprazole) or tramadol (18.2 [6.3-52.8]). Conclusions: Restless legs syndrome is a very rare ADR that was more frequently reported in association with antidepressants, neuroleptics, or tramadol.