Lisdexamfetamine dimesylate improves processing speed and memory in cognitively impaired MS patients: A phase II study

Introduction: Multiple Sclerosis (MS) is known to cause cognitive impairment commonly presenting as slowed processing speed and problems with learning and memory. Stimulants such as amphetamines are attractive candidates for improving mental speed but carry risk for addiction and other adverse behavioral effects. Lisdexamfetamine dimesylate (LDX) is a prodrug currently approved for attention deficit (hyperactivity) disorder (ADHD) with the potential to be better tolerated due to its prolonged clinical effect. Methods: This phase II placebo‐controlled, double‐blind study aimed to assess the safety and efficacy of LDX in cognitively impaired MS patients. Subjects were ages 18‐56 with clinically definite MS impaired on either of the primary outcomes, the Symbol Digit Modalities Test (SDMT) or Paced Auditory Serial Addition Test (PASAT), measures of processing speed. Sixtythree subjects were randomized to 30mg of LDX or placebo in a 2:1 fashion; the dose was increased as tolerated to 70mg over four weeks and then maintained for another four weeks. Secondary outcomes were the Brief Visuospatial Memory Test Revised (BVMTR), the California Verbal Learning Test (CVLT2) both measures of memory, and the Behavioral Rating Inventory of Executive Function for adults (BRIEF‐A), a self‐report measure of executive function. Fatigue and depression were also evaluated. Results: There was significant improvement on the SDMT (+4.8 vs. +1.3) and CVLT2 (+4.7 vs. ‐0.9) in the LDX group vs. placebo in the 49 completers. There was no change on the BRIEF‐A or on self‐reported measures of fatigue and depression. A high proportion of both LDX and placebo subjects reported adverse events (73.5 vs. 68.4%). However there were no serious adverse events noted in the study. Conclusion: LDX shows the potential to be an efficacious treatment for MS patients with cognitive impairment.