Methylphenidate for gait impairment in Parkinson disease

Background: There is a paucity of therapies for gait impairment in Parkinson disease (PD). Open-label studies have suggested improved gait after treatment with methylphenidate (MPD).

Objective: To evaluate the efficacy of MPD for the treatment of gait impairment in PD.

Methods: Twenty-seven subjects with PD and moderate gait impairment were screened for this 6-month placebo-controlled, double-blind study. Subjects were randomly assigned to MPD (maximum, up to 80 mg/day) or placebo for 12 weeks and crossed over after a 3-week washout. The primary outcome measure was change in a gait composite score (stride length + velocity) between groups at 4 and 12 weeks. Secondary outcome measures included changes in motor function, as measured by the Unified Parkinson's Disease Rating Scale (UPDRS), Freezing of Gait Questionnaire (FOGQ), number of gait-diary freezing episodes, and measures of depression, sleepiness, and quality of life. Three-factor repeated-measures analysis of variance was used to measure changes between groups.

Results: Twenty-three eligible subjects with PD were randomized and 17 completed the trial. There was no change in the gait composite score or treatment or time effect for any of the variables. Treatment effect was not modified by state or study visit. Although there was a trend for reduced frequency of freezing and shuffling per diary, the FOGQ and UPDRS scores worsened in the MPD group compared to placebo. There was a marginal improvement in some measures of depression.

Conclusions: MPD did not improve gait and tended to worsen measures of motor function, sleepiness, and quality of life.

Classification of evidence: This study provides Class III evidence for the lack of benefit of MPD on PD-associated gait impairment. Clinical trial registration: NCT00526630.