Efficacy and tolerability of a 20-mg dose of methylphenidate for the treatment of daytime sleepiness in adult patients with myotonic dystrophy type 1: a 2-center, randomized, double-blind, placebo-controlled, 3-week crossover trial

Background: Despite the fact that excessive daytime sleepiness (EDS) is one of the most common manifestations in patients with myotonic dystrophy type 1 (DM1), no treatment is yet available. Methylphenidate is being studied for prospective use in the treatment of EDS.

Objective: The aim of this investigator-initiated study was to evaluate the efficacy and tolerability of a single 20-mg morning dose of methylphenidate for the treatment of EDS in adults with DM1.

Methods: This randomized, double-blind, placebo-controlled, 3-week crossover trial was conducted at 2 sites in Quebec. French-Canadian patients with DM1 with an Epworth Sleepiness Scale score ≥10 were invited to participate in this crossover trial of 20 mg/d of methylphenidate versus placebo, with 3 weeks in each arm of the study separated by a 2-week washout period. The primary efficacy end points were the Daytime Sleepiness Scale and the Epworth Sleepiness Scale at week 3. Secondary end points included the energy/vitality scale of the RAND 36-Item Health Survey, the Profile of Mood States questionnaire, and the mean sleep latency test. Assessment of tolerability profile included a physical examination, measurement of blood pressure, standard 12-lead ECG, and laboratory tests. Adverse event assessments were recorded based on patient reporting at each visit on clinical report forms.

Results: In a total of 24 patients (12 men, 12 women; mean [SD] age, 46 [13] years), 17 completed the study. Treatment with methylphenidate showed a significant change in median scores on the Daytime Sleepiness Scale (-3.0 vs -0.5; P = 0.003) and the Epworth Sleepiness Scale (-3.0 vs -1.5; P = 0.039). The Profile of Mood States and the energy/vitality scale from the RAND 36-Item Health Survey showed no significant changes. Likewise, there was no significant change in mean sleep latency test results. One patient died during the trial, but the autopsy results eliminated methylphenidate as cause of death. Three patients discontinued methylphenidate due to treatment-emergent adverse events (1, diarrhea; 2, nervousness and irritability). Loss of appetite, nausea, and palpitations were the most common adverse events reported by more patients treated with methylphenidate than those receiving placebo.

Conclusion: A single 20-mg dose of methylphenidate significantly reduced daytime sleepiness in this small selected population of patients with DM1. ClinicalTrials.gov identifier: NCT01421992.