Mixed-amphetamine salts, extended release for cognitive impairment in persons with MS, a randomized controlled trial

Cognitive impairment (CI) is a common in persons with MS (PwMS); information processing speed (IPS) is frequently affected. To date, there are no approved therapies to treat CI, or IPS impairment, in PwMS, although preliminary data suggests that amphetamines may be effective. This double-blind, placebo-controlled, multi-center randomized study aimed to evaluate mixed-amphetamine salts, extended release (MAS-XR, or Adderall XR) in PwMS over 12 weeks.

We randomized PwMS demonstrating impairment on the Symbol Digit Modalities Test (SDMT), the primary outcome, to 10 mg MAS-XR, 20 mg MAS-XR or placebo (1:1:1). Measures of memory and questionnaires regarding cognition, depression/anxiety, fatigue, and quality of life, were secondary outcomes. Analysis of covariance (ANCOVA), with baseline scores used as covariates, compared SDMT and other outcomes at 12 weeks.

Between August 2016 and July 2024, 134 potential subjects were screened. 123 entered the study and were randomized; 109 (placebo-44, 10mg-31, 20mg-34) completed the study. The 3 groups were not well matched on age, which was subsequently included in the analysis as a covariate. Baseline SDMT was not significantly different between groups (p = 0.765). At 12 weeks, there was no significant difference on the SDMT between groups (p = 0.545) or comparing placebo to both treatment groups combined (p = 0.945). There was a significant difference over 12 weeks on the MFIS-cognitive (p = 0.018) and MFIS-psychosocial (p = 0.018), as well as on the SF-36 (20 mg MAS-XR group compared to the placebo group (p = 0.041)).

This study does not support the use of amphetamines, specifically MAS-XR, as a treatment for CI or IPS in PwMS.