Safety and efficacy of memantine for multiple sclerosis-related fatigue: A pilot randomized, double-blind placebo-controlled trial

Fatigue is one of the most common symptoms in patients with multiple sclerosis (MS). Currently, there is no approved medication for MS-related fatigue. In this study, we aim to evaluate the safety and efficacy of memantine for improving fatigue in patients with MS. This was a pilot randomized, double-blind, placebo-controlled clinical trial. Eligible patients with relapsing-remitting MS (RRMS) according to the McDonald criteria were randomized to receive either memantine (20 mg/day) or placebo and were assessed at baseline and three months after treatment. The change in the severity of fatigue was determined by the Modified Fatigue Impact Scale (MFIS). Sixty-four patients were randomly allocated to the memantine (n = 32) and placebo (n = 32) groups. Sixteen patients in the memantine group and 24 patients in the placebo group completed the study. The mean [95% CI] absolute change in MFIS scores from baseline did not differ significantly between the memantine (−5.8 [−12.7 to 1.0]) and placebo (−4.0 [−10.6 to 2.7]) groups (between-group difference: −1.9 [−11.7 to 7.8], P = .702). No serious adverse events were reported, except for dizziness and sedation in four patients in the experimental arm, which resulted in discontinuation. This trial failed to prove any clinical efficacy of memantine for the management of MS-related fatigue. Although memantine was generally well-tolerated, adverse events were among the major causes of dropout in this study. •This pilot study investigated the safety and efficacy of memantine in patients with multiple sclerosis (MS)-related fatigue.•No serious adverse events were observed during the 3-month of study.•The results did not support the efficacy of memantine for the treatment of MS-related fatigue.•The findings suggest that memantine has no significant impact on the cognitive profile of patients with MS.