L-amphetamine improves memory in MS patients with objective memory impairment

Background: Memory impairment is prevalent in multiple sclerosis (MS), but no drugs are approved to treat these memory problems. Objective: The objective of the study was to examine the effect of l-amphetamine versus placebo on auditory/verbal memory and visual/spatial memory in MS patients with and without baseline memory impairment. Methods: We conducted a re-analysis of a previously published clinical trial in which MS patients were randomly assigned to treatment (30 mg l-amphetamine, N = 99) or placebo (N = 37) in a four-week, double-blind, parallel-group, dose titration trial. Auditory/verbal memory (CVLT-II: Long Delay Free Recall) and visual/spatial memory (BVMT-R: Delayed Recall) were assessed at baseline and follow-up across subgroups of patients with intact baseline memory (mean = 50th percentile) or impaired baseline memory (mean = 2nd percentile). Primary analyses: 2 (l-amphetamine, placebo) x 2 (baseline, follow-up), x 2 (baseline memory intact, baseline memory impaired) ANOVAs performed separately for auditory/verbal and visual/spatial memory. Results: For both auditory/verbal and visual/spatial memory, we observed significant 2 x 2 x 2 interactions whereby l-amphetamine improved memory more than placebo, and this effect was specific to patients with baseline memory impairment. Conclusions: Among memory-impaired patients, memory improved about 48.5% for those on l-amphetamine, but only 1.0% on placebo. Treatment with l-amphetamine produced large memory gains among memory-impaired MS patients.