L-Dopa-induced sedation: a double-blind cross-over controlled study versustriazolam and placebo in healthy volunteers

Incidental case reports suggest that some parkinsonian patients treated wit h dopaminergic drugs complain of drowsiness but few controlled data are ava ilable. We compared the sedative effects of L-Dopa (200 mg + 50 mg benseraz ide, PO), triazolam (0.125 mg) and placebo in a randomized double-blind cro ss-over design in 22 healthy volunteers pretreated with domperidone (60 mg/ day). Drowsiness was assessed using a visual analog scale (VAS), a computer ized choice reaction time test (CRT) and an electro-oculogram (EOG). L-Dopa and triazolam induced significant drowsiness, compared to placebo, on VAS, CRT and some EOG parameters. After this first evaluation session, all subj ects were chronically treated for Il days with 600 mg/d of L-Dopa. Drowsine ss induced by L-Dopa, triazolam or placebo was then tested again on three c onsecutive days to assess putative dopaminergic tolerance. After chronic L- Dopa treatment, triazolam-induced sedation remained unchanged while L-Dopa sedative effects were no longer significant except on the VAS, preventing t he conclusion that tolerance occurred. These data suggest that an acute dos e of L-Dopa induces sedation in L-Dopa-naive subjects. This sedative effect must be considered in clinical practice and when studying the effects of L -Dopa on motor or neuropsychological performance, especially in acute tests .