Lisdexamfetamine dimsylate improves cognition in MS

EpubMorrow et al. Lisdexamfetamine dimesylate improves processing speed and memory in cognitively impaired MS patients: a phase II study. J Neurol. 2012 Sep 23.

Background: MS causes cognitive impairment including slowed processing speed and problems with learning and memory. Stimulants are attractive candidates for improving mental speed but carry risk of addiction and other adverse behavioral effects. Lisdexamfetamine dimesylate (LDX) is a D-amphetamine prodrug currently approved for attention deficit (hyperactivity) disorder 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 MSers. Subjects were MSers with clinically definite MS, aged 18-56 years, and impaired on either of two primary outcomes: the Symbol Digit Modalities Test (SDMT) or the Paced Auditory Serial Addition Test (PASAT). Both SDMT and PASAT are measures of cognitive processing speed. Of 174 MSers  screened, 63 were randomized to 30 mg of LDX or placebo in a 2:1 fashion; the dose was increased as tolerated to 70 mg over 4 weeks and then maintained for another 4 weeks. Secondary outcomes were the Brief Visuospatial Memory Test Revised (BVMTR), the California Verbal Learning Test 2nd edition (CVLT2), both measures of episodic 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 in the SDMT score (+4.6 vs. +1.3) and CVLT2 score (+4.7 vs. -0.9) in the LDX group compared with the placebo group among the 49 completers. There was no change on the other outcomes. A high proportion of both LDX-treated and placebo-treated subjects reported adverse events (73.5 % vs. 68.4 %). However, there were no serious adverse events noted in the study.

Conclusion: These preliminary data indicate that LDX has the potential to be an efficacious treatment for MSers with cognitive impairment.


“Please don’t get bogged down with the names of the cognitive tests used in this study. They are standardised tests they are validated in MS.”

“This study is good news for several reasons: (1) Investigators and Pharma are interested in MS-related cognition; Big Pharma have the resources and drugs to find a treatment for this problem; (2) each trial is an experiment testing and improving on phase 2 trial design; the more exploratory phase 2 trials we do the more quicker we will find a suitable trial design for emerging treatments; (3) this study helps elevate cognitive-impairment is in the minds of MSers, funders and other MS stakeholders; cognitive impairment is a big problem and almost certainly drives early MS impairment and disability – it needs to be in the spotlight; (4) it is trying to improve the lives of MSers; something we all want to do.”
“When I started in neurology we used to use pemoline and amphetamines to treat MS-related fatigue; these were both stimulants. We stopped using them because they exacerbated anxiety and they were scheduled drugs with the potential for abuse. LDX is an amphetamine so I am not sure how good it is going to be – the problems I referred to above will not have gone away. So at the moment we still have to make do with amantadine, modafanil and caffeine! Yes, caffeine; at least it is socially acceptable to be addicted to the stuff.”

“Good news or bad? On balance this trial is very good news!”

4 thoughts on “Lisdexamfetamine dimsylate improves cognition in MS”

  1. Great to see exciting new drugs for symptoms of MS – it's just as important as the DMD work in my view.In terms of cognitive impact – how does this work? Is it like a spinal lesion that might suddenly paraylses my legs – might I wake up one morning and just be notably cognitively impaired or is it a more creeping thing? I had assumed the latter but would be good to understand. Does the fact I am not cognitively impaired at all at the moment (I nailed the 2 sec PASAT lol!) allow me to be reasonably confident of maintaining cognitive integrity over at least the short-medium term (if not long term)?

  2. "might suddenly paraylses my legs"Sorry – that should have read "might suddenly paralyse my legs". And here's me crowing about my cognitive abilities… 😉

  3. Re: "notably cognitively impaired or is it a more creeping thing?"Not necessarily; I have seen some MSers present with a cognitive relapse that gets better as the recover. This, however, is rare. Most of the time the cognitive impairments creep and you don't notice them as your brain adapts. They tend to become noticeable when you are at work or someone tests for the deficits.

  4. re 'make do with amantadine, modafanil and caffeine' : how useful is caffeine when compared with modafanil etc?

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