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Lisdexamfetamine dimesylate improves processing speed and memory in cognitively impaired MS patients: a phase II study

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Abstract

Multiple sclerosis (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. This phase II placebo-controlled, double-blind study aimed to assess the safety and efficacy of LDX in cognitively impaired MS patients. Subjects were patients 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 MS patients 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. 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. These preliminary data indicate that LDX has the potential to be an efficacious treatment for MS patients with cognitive impairment.

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Acknowledgments

This study was funded by Shire Development LLC as an investigator-initiated trial.

Conflicts of interest

Dr. Morrow has participated in speaker’s bureaus and/or served as a consultant for Bayer, Biogen Idec, EMD Serono, Teva Neurosciences and Novartis. She has also received grant/research support from Biogen Idec and Novartis. She has no other industry financial relationships. Dr. Smerbeck, Dr. Cookfair and Ms. Patrick have nothing to disclose. Dr. Weinstock-Guttman has participated in speaker’s bureaus and served as a consultant for Biogen Idec, Teva Neurosciences, EMD Serono, Pfizer, Novartis, Genzyme and Accorda. Excluding Genzyme, she has also received grant/research support from the agencies listed above as well as ITN, Questcor and Shire. She has no other industry financial relationships. Dr. Ralph Benedict has served as a consultant for Actelion, Biogen Idec, Bayer and Novartis. He has also received grant/research support from Accorda, Biogen Idec and Shire. He also receives royalties from Psychological Assessment Resources. He has no other industry financial relationships.

Ethical standard

This study has been approved by the appropriate ethics committee and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.

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Authors and Affiliations

  1. Department of Clinical Neurological Sciences, Western University, B10-105, LHSC-UH, 339 Windermere Road, London, ON, N6A 5A5, Canada

    Sarah A. Morrow

  2. Department of Neurology, SUNY Buffalo School of Medicine, MS Center at the Jacobs Neurological Institute, Buffalo General Hospital, Suite E2, 100 High Street, Buffalo, NY, 14203, USA

    Audrey Smerbeck, Kara Patrick, Diane Cookfair, Bianca Weinstock-Guttman & Ralph H. B. Benedict

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  1. Sarah A. Morrow
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  6. Ralph H. B. Benedict
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Correspondence to Ralph H. B. Benedict.

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Morrow, S.A., Smerbeck, A., Patrick, K. et al. Lisdexamfetamine dimesylate improves processing speed and memory in cognitively impaired MS patients: a phase II study. J Neurol 260, 489–497 (2013). https://doi.org/10.1007/s00415-012-6663-7

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