Examining the effectiveness of acetylcholinesterase inhibitors and stimulant-based medications for cognitive dysfunction in multiple sclerosis: A systematic review and meta-analysis

We sought to examine the effectiveness of acetylcholinesterase inhibitors (AChEIs) and stimulant-based medications for improving cognitive performance in patients with multiple sclerosis (MS). An electronic database search was conducted on 25th March 2017. Eligible studies were double-blind, randomised, placebo-controlled trials that examined the efficacy of compounds that act primarily as AChEIs or stimulants (administered daily for ≥1 week) on cognitive outcome measures in patients with MS. Where suitable data was reported, we generated effect sizes and corresponding 95% confidence intervals and performed meta-analyses using random-effects models to investigate the effectiveness of these drug types across cognitive domains. Sixteen trials were included in the systematic review, with eleven trials (N = 734 MS patients) providing sufficient data for meta-analysis. Whilst there was only a limited pool of relatively small trials and a number of different compounds, we found that collectively, both AChEIs (donepezil and rivastigmine) and stimulants (methylphenidate, modafinil, l-amphetamine sulfate and lisdexamfetamine dimesylate) offered no significant benefits over placebo on measures of processing speed, working memory, verbal fluency, verbal memory, visuospatial memory or executive functioning.