Methylphenidate for gait hypokinesia and freezing in patients with Parkinson's disease undergoing subthalamic stimulation: a multicentre, parallel, randomised, placebo-controlled trial
The Lancet Neurology, 06/22/2012
Moreau C et al. – Methylphenidate improved gait hypokinesia and freezing in patients with advanced Parkinson's disease receiving subthalamic nucleus stimulation. Methylphenidate represents a therapeutic option in the treatment of gait disorders at the advanced stage of Parkinson's disease.Methods
- This multicentre, parallel, double–blind, placebo–controlled, randomised trial was done in 13 movement disorders departments in France between October, 2009, and December, 2011.
- Eligible patients were younger than 80 years and had Parkinson's disease, severe gait disorders, and freezing of gate despite optimised treatment of motor fluctuations with dopaminergic drugs and subthalamic stimulation.
- The authors randomly assigned patients (1:1 with a computer random–number generator in blocks of four) to receive methylphenidate (1 mg/kg per day) or placebo capsules for 90 days.
- Patients, their carers, study staff, investigators, and data analysts were masked to treatment allocation.
- To control for confounding effects of levodopa they assessed patients under standardised conditions with an acute levodopa challenge.
- The primary outcome was a change in the number of steps during the stand–walk–sit (SWS) test without levodopa.
- They compared the respective mean numbers of steps at day 90 in the methylphenidate and placebo groups in a covariance analysis and adjusted for baseline differences.
- They screened 81 patients and randomly assigned 35 to receive methylphenidate and 34 to receive placebo.
- 33 patients in the methylphenidate group and 32 patients in the placebo group completed the study.
- Efficacy outcomes were assessed in the patients who completed the study.
- Compared with patients in the placebo group (median 33 steps [IQR 26–45]), the patients in the methylphenidate group made fewer steps at 90 days (31 [26–42], F(1, 62)=6.1, p=0.017, adjusted size effect 0.61).
- Adverse events were analysed in all randomly assigned patients.
- There were significantly more adverse events in the methylphenidate group compared with placebo.
- Patients on methylphenidate had a significant increase in heart rate (mean 3.6 [SD 7.2] beats per min) and decrease in weight (mean 2.2 [SD 1.8] kg) compared with the placebo group.