Effects of single dose mixed amphetamine salts - extended release on processing speed in multiple sclerosis: a double blind placebo controlled study

Multiple sclerosis (MS) commonly affects cognitive function, most frequently presenting as impaired processing speed (PS). There are currently no approved treatments for PS in this population, but previous studies suggest amphetamines may be beneficial. The objective of this study is to determine if mixed amphetamine salts, extended release (MAS-XR) has the potential to improve impaired PS in MS patients in a randomized controlled pre- and post-dose testing study. Fifty-two MS patients demonstrating PS impairment on either the Symbol Digit Modalities Test (SDMT) or Paced Auditory Serial Addition Test (PASAT) were randomized to a single dose of 5 mg MAS-XR (n = 18), 10 mg MAS-XR (n = 20), or placebo (n = 14). Subjects were evaluated a second time, after taking the blinded medication. ANOVA was used to compare the change on the SDMT and PASAT in each of the treatment groups compared to the placebo. Cohen's d was used to calculate effect size. At baseline, the mean SDMT score was 43.3 +/- 7.2 and the mean PASAT was 34.8 +/- 13.4, with 47 (90.4 %) and 25 (48.1 %) categorized as impaired on the SDMT and PASAT, respectively. The change in SDMT scores from baseline to post-treatment demonstrated significant improvement for the MAS-XR 10-mg dose compared to placebo, increasing by 5.2 +/- 4.5 vs. 0.6 +/- 4.4 points (p = 0.043), with a medium effect size of 0.47. Change on the PASAT was not significantly different in either treatment group. This study supports MAS-XR 10 mg as a potential treatment for MS patients with demonstrated PS impairment, warranting a larger longitudinal study.