Journal of Neurology

, Volume 256, Issue 7, pp 1095–1102 | Cite as

The effects of l-amphetamine sulfate on cognition in MS patients: results of a randomized controlled trial

  • Sarah A. Morrow
  • Tanya Kaushik
  • Peter Zarevics
  • David Erlanger
  • Mark F. Bear
  • Frederick E. Munschauer
  • Ralph H. B. BenedictEmail author
Original Communication


Defects in processing speed and memory are common in multiple sclerosis (MS) patients. In other populations, amphetamines have been shown to enhance cognition, but their use is limited by adverse behavioral effects. The l-isomer may have equivalent cognition enhancement with less adverse effects due to decreased potency in subcortical areas. The aim of this study was to assess the safety and efficacy of l-amphetamine sulfate in the treatment of cognitive dysfunction in MS. This was a 2:1 randomized, placebo-controlled, double-blind trial, involving 33 MS clinics across the USA. One hundred and fifty-one clinically definite MS patients with documented cognitive dysfunction who were relapse free for ≥90 days, with an Expanded Disability Status Scale (EDSS) ≤6.5, and with no other medical/psychiatric condition that may cause psychological dysfunction were randomized to 30 mg of oral l-amphetamine sulfate or placebo for 29 days, including a dose escalation period. A history of cardiac disease, uncontrolled hypertension or electrocardiograph abnormalities resulted in exclusion. The primary outcomes were the Subject Global Assessment of Change and Symbol Digit Modalities Test (SDMT). Secondary outcomes were the results from the California Verbal Learning Test, second edition (CVLT2), Brief Visual Memory Test-Revised (BVMTR), and Paced Auditory Serial Addition Test (PASAT). One hundred and thirty-six subjects completed the study. No differences were found at baseline in demographics or in the results of the neuropsychological tests. After treatment, the active group performed significantly better for total learning (P = 0.041) and delayed recall (P < 0.01) on the BVMTR, and for delayed recall (P = 0.012) on the CVLT2. Five patients (four from the treatment group, one placebo) withdrew due to intolerable adverse events. l-amphetamine sulfate was associated with improved learning and memory and was well tolerated in this study. However, because the positive findings were observed on secondary outcome measures, the study requires replication before l-amphetamine sulfate can be recommended for the treatment of cognitive impairment in MS.


Adverse events Amphetamines l-amphetamine sulfate Cognition enhancement Cognitive impairment Multiple sclerosis 



This trial was sponsored by Cognition Pharmaceuticals, LLC. The authors would like to acknowledge the primary investigators at each participating site: R. Aung-din, Sarasota FL, J. Berger, Lexington KY, M. Cascione, Tampa FL, S. Elias, Detroit MI, B. Evans Traverse City MI, C. Ford, Albuquerque NM, E. Fox, Round Rock TX, S.M. Freedman, Raleigh NC, S. Gazda San Antonio TX, D. Giang, Loma Linda CA, D. Greco Danbury CT, J. Gross, Fairfield CT, W. Honeycutt, Maitland FL, G. Hutton, Houston, TX, A. Keegan, Sarasota FL, K. Kresa-Reahl, Charleston WV, T. Leist, Philadelphia PA, S. Lynch, Kansas City KS, A. Mazhari, Akron OH, F. Munchauer, Buffalo NY, J. Preiningerova New Haven CT, S. Rizvi, Providence RI, V. Rowe, Lenexa CT, S. Scarberry, Fargo ND, M. Shcmerler, Cinncinnati OH, J. Shi, Charlottesville VA, H. Sullivan, Grand Rapids MI, C. Thiagarajah, Lancaster CA, B. Thrower Atlanta GA, S. Thurston, Richmond VA, A. Vasquez, St. Petersburg FL, J. Wendt, Tuscon AZ.

Conflict of interest statement

Dr. Morrow has no conflict of interest or financial disclosures related to this project.

Dr. Kaushik supervised the trial on behalf of the sponsor company.

Mr. Zarevics served as consultant for trial design and management on behalf of the sponsor company.

Dr. Erlanger has financial interest in the sponsor company.

Dr. Bear has no conflict of interest or financial disclosures related to this project.

Dr. Munschauer has no conflict of interest or financial disclosures related to this project.

Dr. Benedict received financial support from Cognition Pharmaceuticals LLC, to support his role as PI in this study.

This trial was registered with


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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Sarah A. Morrow
    • 1
  • Tanya Kaushik
    • 2
  • Peter Zarevics
    • 3
  • David Erlanger
    • 4
  • Mark F. Bear
    • 5
  • Frederick E. Munschauer
    • 1
  • Ralph H. B. Benedict
    • 1
    Email author
  1. 1.Jacobs Neurological InstituteState University of New York at BuffaloBuffaloUSA
  2. 2.Clinical Affairs PanMedix Inc.New YorkUSA
  3. 3.Clinical Operations Seaside TherapeuticsPhiladelphiaUSA
  4. 4.Cognition Pharmaceuticals, LLCNew YorkUSA
  5. 5.Massachusetts Institute of Technology (MIT), Department of Brain and Cognitive Sciences InvestigatorHoward Hughes Medical InstituteCambridgeUSA

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