Methylphenidate off-label use and safety

INTRODUCTION Methylphenidate is a piperidine derivative structurally and pharmacologically similar to amphetamine. Methylphenidate is indicated for Attention Deficit Hyperactivity Disorder (ADHD) in children aged 6 years of age and over when remedial measures alone prove insufficient. In adults, its indication, except in narcolepsy, is not defined. Methylphenidate received regulatory approval almost sixty years ago with a first registration in Switzerland in October 1954. OBJECTIVE To evaluate the off-label use of methylphenidate and its characteristics from a database of spontaneous reports. METHODS This study analysed data from the French Pharmacovigilance Database of adverse drug reactions spontaneously reported by health professionals from 1985 to December 2011. Off-label use was evaluated according to age. RESULTS In the French Pharmacovigilance database, 181 cases of adverse drug reactions were reported with methylphenidate. Neuropsychiatric effects were the most frequent adverse event reported (41%) followed by cardiovascular and cutaneous side effects (14%). 143 reports concerned children (113 boys, 30 girls, mean age 10.6 ± 3.3 years) of which 46 (30%) were off-label uses. There were 38 adults (20 men, 18 women), of which 32 (88%) off-label use. In adults, methylphenidate was prescribed for depression, and this practice was associated with serious adverse events of drug dependence, overdose and suicide attempt. Overall, off-label use was detected in 43% (78/181) of all cases reported. CONCLUSION More than 40% of the patients with drug reactions received methylphenidate for off-label indications. Additional long-term exposures and independent clinical studies are necessary to establish the long-term profile safety of methylphenidate.