Methylphenidate Increases the Motor Effects of L-Dopa in Parkinson's Disease: A Pilot Study

Abstract

We determined whether methylphenidate, a dopamine transporter blocker, modifies motor, cognitive, or affective responses to L-Dopa in Parkinson's disease (PD). Five patients who reported benefit from L-Dopa/carbidopa and motor fluctuations were admitted and withdrawn from their usual antiparkinsonian medications. On 3 consecutive days in a randomized double-blinded fashion, they took 0.2 mg/kg oral methylphenidate or placebo followed 30 minutes later by a 1-hour intravenous L-Dopa (2 mg/kg per h) or placebo infusion. Vital signs, tapping, walking, dyskinesias, mood, anxiety, concentration, and arousal were monitored every 30 minutes. Cognitive testing was performed before and following the infusion. Methylphenidate combined with L-Dopa led to greater peak right-hand tapping speed than either alone. Dyskinesia severity increased most when methylphenidate and L-Dopa were co-administered. There were no differences between conditions on the Stroop test, digit ordering, simple reaction time, or covert orienting of attention validity effect. Methylphenidate alone led to improvement in choice reaction time. Change in self-assessed analogue ratings of mood, anxiety, arousal, or concentration did not differ between conditions. Methylphenidate increased the motor effects of L-Dopa with minimal effects on cognitive or affective functions, suggesting a physiologic role for the dopamine transporter in patients with PD with motor fluctuations.

The Role of Higher-Level Cognitive Function in Gait: Executive Dysfunction Contributes to Fall Risk in Alzheimer’s Disease

“…Results of a pilot study (n = 5) to determine the effects of methylphenidate as an adjunct to L -DOPA in Parkinson's disease (PD) demonstrated an increase in the motor effects of L -DOPA with the addition of methylphenidate. There were minimal effects on cognition and affect (with the exception of reaction time) [106] . Chronic administration of nicotine via transdermal patch has been found to have positive effects on cognition in AD and MCI, particularly in the subset of attention [107] .…”

Gait dynamics in Parkinson’s disease: Common and distinct behavior among stride length, gait variability, and fractal-like scaling

“…Because dopamine reuptake plays an important role in the regulation of dopamine in the synapse and the hypodopaminergic state is at the basis of much of the Parkinsonian syndrome, it has been suggested that MPH can improve motor function in PD. [135][136][137] Given the decline in attention abilities in PD and the putative reliance of a steady gait on this cognitive domain ͑recall the profound dual tasking effects͒, we hypothesized that MPH may also improve gait and reduce fall risk in patients with PD. 65 Twenty-one patients with PD were studied before and 2 h after administration of a single dose of 20 mg MPH.…”

The dopamine transporter: Importance in Parkinson's disease

“…These findings confirmed the results of our pilot study. 31 However, a study of another DAT inhibitor, branofensine, failed to find any effect of DAT inhibition on the response to an oral dose of L-dopa in eight PD subjects. 32 Differences in subjects and methods may explain the different results.…”