Acute effects of immediate and controlled-release levodopa on mood in Parkinson's disease: A double-blind study

Mood fluctuations related to levodopa (LD) dosing are well-known psychiatric complications of Parkinson's disease (PD). No formal studies explored how affective response to LD relates to the type of motor response to oral LD (stable or wearing-off) and to different pharmacokinetic profiles of oral LD. We used an intrasubject randomized double-blind crossover design to study 14 patients (7 stable, 7 wearing-off) who were monitored for motor status, mood, anxiety, and plasma LD levels 1 hour before and 6 hours after an oral dose of immediate-release (IR) and controlled-release LD formulations. Analysis of the dose-response curves showed a significant interaction between the type of motor response and the type of LD. Only the wearing-off patients had a significant mood elevation, and this effect was only significant following challenge with IR LD. Motor status strongly correlated with LD plasma levels and anxiety but not with mood ratings. Mood changes in PD patients are related to the patient's type of motor response to oral LD and also to the kinetic profile of the LD formulation used for dopaminergic replacement.