High dose methylphenidate in the treatment of freezing of gait in advanced Parkinson’s disease

Abstract

Background

Freezing of gait (FoG) is one of the most incapacitating symptoms of Parkinson’s disease (PD) and has been linked to imbalances in the dopaminergic and noradrenergic neurotransmitter systems. Methylphenidate blocks the reuptake of these neurotransmitters, increasing their extracellular concentrations in the striatum and prefrontal cortex. This quantitative pooled analysis was aimed at determining the efficacy and safety of high dose methylphenidate in the treatment of FoG, motor and non-motor symptoms in advanced PD.

Methods

Electronic databases were searched for randomized, double-blind, placebo-controlled trials examining the efficacy and safety of methylphenidate (0.8–1.0 mg/kg/day) in FoG. Fixed effects analysis with mean difference of number of freezing episodes was used as primary outcome. Secondary outcomes included Unified Parkinson Disease Rating Scale (UPDRS) Part III score, Montgomery-Asberg Depression Rating Scale (MADRS) score, Epworth Sleepiness Scale (ESS) score and incidence of adverse events.

Results

Two studies were included with a total of 92 patients. High dose methylphenidate was able to reduce the number of freezing episodes with a MD −1.52 (95% CI −2.91, −0.11, p = .03). However, the drug was not able to offer significant improvement in terms of UPDRS Part III score in the “off” (MD −1.87; 95% CI −6.42, 2.69, p = .40) and the “on” state (MD 1.38; 95% CI −2.91, −0.11, p = 0.54), MADRS Score (MD −0.38, 95% CI −2.37, 1.60, p = .35) and ESS Score (MD −1.09, 95% CI −3.44, 1.26, p = .68). A small but statistically significant proportion of patients given high dose methylphenidate reported nausea, vomiting, and gastritis (MD 4.86, 95% CI 1.15, 20.56, p = .03)

Conclusion

High dose methylphenidate can only marginally, however significantly reduce the number of freezing episodes in patients with advanced PD with a MD −1.52 (95% CI −2.91, −0.11, p = .03).