Lisdexamfetamine dimesylate improves processing speed and memory in cognitively impaired MS patients: a phase II study
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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Some aspects of executive functioning in patients with neurocognitive deficits caused by diseases other than ADHD have been shown to improve with administration of stimulants.
“some aspects of executive functioning in patients with neurocognitive deficits caused by diseases other than ADHD have been shown to improve with administration of stimulants [32], [33].”
From Atomoxetine Effects on Executive Function as Measured by the BRIEF-A in Young Adults with ADHD: A Randomized, Double-Blind, Placebo-Controlled Study (2014) · cites this paper as [32]
Cites
Paced Auditory Serial-Addition Task: A Measure of Recovery from Concussion
Gronwall, D. M. A. (1977) · Perceptual and Motor Skills · doi:10.2466/pms.1977.44.2.367 · Cited by 2,395 · see citing works
Benedict, R. H. B., Wahlig, E., Bakshi, R., Fishman, I., Munschauer, F., Zivadinov, R., & Weinstock-Guttman, B. (2005) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2004.12.009 · Cited by 528 · see citing works
Self-citationPharmacological treatments for fatigue associated with palliative care
Mücke, M., Mochamat, M., Cuhls, H., Peuckmann-Post, V., Minton, O., Stone, P., & Radbruch, L. (2015) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd006788.pub3 · Cited by 227 · see citing works
Magill, R. A., Waters, W. F., Bray, G. A., Volaufova, J., Smith, S. R., Lieberman, H. R., McNevin, N., & Ryan, D. H. (2003) · Nutritional Neuroscience · doi:10.1080/1028415031000120552 · Cited by 114 · cited 1× · see citing works
“Amphetamines also enhance executive function, attention and working memory in patients with schizophrenia [18, 19] and after sleep deprivation [20, 21].”
Background
Flagged first, then by citations
Cited by
Sorted by citations
Salagre, E., Solé, B., Tomioka, Y., Fernandes, B. S., Hidalgo-Mazzei, D., Garriga, M., Jimenez, E., Sanchez-Moreno, J., Vieta, E., & Grande, I. (2017) · Journal of Affective Disorders · doi:10.1016/j.jad.2017.06.034 · Cited by 71 · see citing works
Novel pharmacologic treatment in acute binge eating disorder – role of lisdexamfetamine
Guerdjikova, A. I., Mori, N., Casuto, L. S., & McElroy, S. L. (2016) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s80881 · Cited by 40 · see citing works
Dolder, P. C., Strajhar, P., Vizeli, P., Odermatt, A., & Liechti, M. E. (2018) · Psychopharmacology · doi:10.1007/s00213-018-4849-0 · Cited by 34 · see citing works
Adler, L. A., Clemow, D. B., Williams, D. W., & Durell, T. M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0104175 · Cited by 32 · see citing works
- Authors
- Morrow, S. A., Smerbeck, A., Patrick, K., Cookfair, D., Weinstock-Guttman, B., & Benedict, R. H. B.
- Affiliations
- Western University (CA)
- Jacobs Institute (US)
- Corresponding author
- Benedict, Ralph H. B.
- Venue
- Journal of Neurology
- Published
- 2012-09-23
- Volume
- 260
- Issue
- 2
- Pages
- 489-497
- ISSN
- 0012-1037 (ISSN-L)
- 0340-5354
- 1432-1459
- OpenAlex
- W2008283574
- Cited by
- 40
- References
- 4
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 7 · 2015: 3 · 2014: 5 · 2013: 5
- FWCI
- 3.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Biogen
- Teva Pharmaceutical Industries
- IC Design Education Center
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
- Keywords
- lisdexamfetamine dimesylate, multiple sclerosis, cognitive impairment, processing speed, memory, stimulants, executive function, fatigue, depression, adverse events, Symbol Digit Modalities Test, Paced Auditory Serial Addition Test, Brief Visuospatial Memory Test-Revised, California Verbal Learning Test
- MeSH terms
- Lisdexamfetamine Dimesylate, Adolescent, Adult, Central Nervous System Stimulants, Analysis of Variance, Cognition Disorders, Dextroamphetamine, Disability Evaluation, Double-Blind Method, Female, Humans, Male, Memory, Mental Processes, Middle Aged, Multiple Sclerosis, Neuropsychological Tests, Retrospective Studies, Statistics, Nonparametric, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
