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Psychopharmacology

, Volume 232, Issue 23, pp 4253–4259 | Cite as

Effects of single dose mixed amphetamine salts - extended release on processing speed in multiple sclerosis: a double blind placebo controlled study

  • Sarah A. MorrowEmail author
  • Heather Rosehart
Original Investigation

Abstract

Rationale

Multiple sclerosis (MS) commonly affects cognitive function, most frequently presenting as impaired processing speed (PS). There are currently no approved treatments for PS in this population, but previous studies suggest amphetamines may be beneficial.

Objective

The objective of this study is to determine if mixed amphetamine salts, extended release (MAS-XR) has the potential to improve impaired PS in MS patients in a randomized controlled pre- and post-dose testing study.

Methods

Fifty-two MS patients demonstrating PS impairment on either the Symbol Digit Modalities Test (SDMT) or Paced Auditory Serial Addition Test (PASAT) were randomized to a single dose of 5 mg MAS-XR (n = 18), 10 mg MAS-XR (n = 20), or placebo (n = 14). Subjects were evaluated a second time, after taking the blinded medication. ANOVA was used to compare the change on the SDMT and PASAT in each of the treatment groups compared to the placebo. Cohen’s d was used to calculate effect size.

Results

At baseline, the mean SDMT score was 43.3 ± 7.2 and the mean PASAT was 34.8 ± 13.4, with 47 (90.4 %) and 25 (48.1 %) categorized as impaired on the SDMT and PASAT, respectively. The change in SDMT scores from baseline to post-treatment demonstrated significant improvement for the MAS-XR 10-mg dose compared to placebo, increasing by 5.2 ± 4.5 vs. 0.6 ± 4.4 points (p = 0.043), with a medium effect size of 0.47. Change on the PASAT was not significantly different in either treatment group.

Conclusions

This study supports MAS-XR 10 mg as a potential treatment for MS patients with demonstrated PS impairment, warranting a larger longitudinal study.

Keywords

Multiple sclerosis Randomized clinical trial Cognitive impairment Processing speed Amphetamine Treatment 

Abbreviations

ADHD

Attention deficit hyperactivity disorder

BDIFS

Beck Depression Inventory-Fast Screen

BiCAMS

Brief International Cognitive Assessment for MS

BRNB

Brief Repeatable Neuropsychological Battery

CI

Cognitive impairment

EDSS

Expanded Disability Status Scale

FSS

Fatigue Severity Scale

IR

Immediate release

MACFIMS

Minimal Assessment of Cognitive Function in MS

MAS-XR

Mixed amphetamine salts, extended release

MS

Multiple sclerosis

MSFC

Multiple Sclerosis Functional Composite

PASAT

Paced Auditory Serial Addition Test

PPMS

Primary progressive multiple sclerosis

PS

Processing speed

RRMS

Relapsing remitting multiple sclerosis

SD

Standard deviation

SDMT

Symbol Digit Modalities Test

SPMS

Secondary progressive multiple sclerosis

XR

Extended release

Notes

Study funding

Funding was provided by the Internal Research Fund (IRF), Department of Clinical Neurological Sciences, Western University.

Conflict of interest

The authors declare that they have no competing interests.

References

  1. Amato MP, Ponziani G, Siracusa G, Sorbi S (2001) Cognitive dysfunction in early-onset multiple sclerosis: a reappraisal after 10 years. Arch Neurol 58(10):1602–1606CrossRefPubMedGoogle Scholar
  2. Barch DM, Carter CS (2005) Amphetamine improves cognitive function in medicated individuals with schizophrenia and in healthy volunteers. Schizophr Res 77(1):43–58CrossRefPubMedGoogle Scholar
  3. Beatty WW, Blanco CR, Wilbanks SL, Paul RH (1995) Demographic, clinical, and cognitive characteristics of multiple sclerosis patients who continue to work. J Neurol Rehab 9:167–173Google Scholar
  4. Benedict RHB, Priore RL, Miller C, Munschauer F, Jacobs L (2001) Personality disorder in multiple sclerosis correlates with cognitive impairment. J Neuropsychiatr Clin Neurosci 13(1):70–76CrossRefGoogle Scholar
  5. Benedict RHB, Fischer JS, Archibald CJ, Arnett PA, Beatty WW, Bobholz J, Chelune G, Fisk JD, Langdon DW, Caruso LS, Foley FW, LaRocca NG, Vowels L, Weinstein A, DeLuca J, Rao SM, Munschauer FE (2002) Minimal neuropsychological assessment of MS patients: a consensus approach. Clin Neuropsychol 16:381–397CrossRefPubMedGoogle Scholar
  6. Benedict RH, Fishman I, McClellan MM, Bakshi R, Weinstock-Guttman B (2003) Validity of the Beck Depression Inventory-Fast Screen in multiple sclerosis. Mult Scler 9(4):393–396CrossRefPubMedGoogle Scholar
  7. Benedict RHB, Wahlig E, Bakshi R, Fishman I, MunschauerF, Zivadinov R, Weinstock-Guttman B (2005) Predicting quality of life in multiple sclerosis: accounting for physical disability, fatigue, cognition, mood disorder, personality, and behavior change. J Neurol Sci 1–2: 29–34Google Scholar
  8. Benedict RH, Cookfair D, Gavett R, Gunther M, Munschauer F, Garg N, Weinstock-Guttman B (2006) Validity of the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS). J Int Neuropsychol Soc 12(4):549–558CrossRefPubMedGoogle Scholar
  9. Benedict RH, Duquin JA, Jurgensen S, Rudick RA, Feitcher J, Munschauer FE, Panzara MA, Weinstock-Guttman B (2008) Repeated assessment of neuropsychological deficits in multiple sclerosis using the Symbol Digit Modalities Test and the MS Neuropsychological Screening Questionnaire. Mult Scler 14(7):940–946CrossRefPubMedGoogle Scholar
  10. Berman SM, Kuczenski R, McCracken JT, London ED (2009) Potential adverse effects of amphetamine treatment on brain and behavior: a review. Mol Psychiatry 14(2):123–142PubMedCentralCrossRefPubMedGoogle Scholar
  11. Biederman J, Lopez FA, Boellner SW, Chandler MC (2002) A randomized, double-blind, placebo-controlled, parallel-group study of SLI381 (Adderall XR) in children with attention-deficit/hyperactivity disorder. Pediatrics 110(2 Pt 1):258–266CrossRefPubMedGoogle Scholar
  12. Carone D, Benedict RHB, Munschauer FE III, Fishman I, Weinstock-Guttman B (2005) Interpreting patient/informant discrepancies of reported cognitive symptoms in MS. J Int Neuropsychol Soc 11:574–583CrossRefPubMedGoogle Scholar
  13. Chiaravalloti ND, DeLuca J (2008) Cognitive impairment in multiple sclerosis. Lancet Neurol 7(12):1139–1151CrossRefPubMedGoogle Scholar
  14. Fischer JS, Rudick RA, Cutter GR, Reingold SC (1999) The Multiple Sclerosis Functional Composite Measure (MSFC): an integrated approach to MS clinical outcome assessment. National MS Society Clinical Outcomes Assessment Task Force. Mult Scler 5(4):244–250CrossRefPubMedGoogle Scholar
  15. Gehring K, Patwardhan SY, Collins R, Groves MD, Etzel CJ, Meyers CA, Wefel JS (2012) A randomized trial on the efficacy of methylphenidate and modafinil for improving cognitive functioning and symptoms in patients with a primary brain tumor. J Neurooncol 107(1):165–174CrossRefPubMedGoogle Scholar
  16. Gronwall DMA (1977) Paced auditory serial addition task: a measure of recovery from concussion. Percept Mot Skills 44:367–373CrossRefPubMedGoogle Scholar
  17. Harel Y, Appleboim N, Lavie M, Achiron A (2008) Single dose of methylphenidate improves cognitive performance in multiple sclerosis patients with impaired attention process. J Neurol Sci 276: 38–40Google Scholar
  18. Heal DJ, Cheetham SC, Smith SL (2009) The neuropharmacology of ADHD drugs in vivo: insights on efficacy and safety. Neuropharmacology 57(7–8):608–618CrossRefPubMedGoogle Scholar
  19. Kim YH, Ko MH, Na SY, Park SH, Kim KW (2006) Effects of single-dose methylphenidate on cognitive performance in patients with traumatic brain injury: a double-blind placebo-controlled study. Clin Rehabil 20(1):24–30CrossRefPubMedGoogle Scholar
  20. Kim J, Whyte J, Patel S, Europa E, Wang J, Coslett HB, Detre JA (2012) Methylphenidate modulates sustained attention and cortical activation in survivors of traumatic brain injury: a perfusion fMRI study. Psychopharmacology (Berlin) 222(1):47–57CrossRefGoogle Scholar
  21. Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD (1989) The Fatigue Severity Scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol 46(10):1121–1123CrossRefPubMedGoogle Scholar
  22. Kujala P, Portin R, Ruutiainen J (1997) The progress of cognitive decline in multiple sclerosis. Brain 120:289–297CrossRefPubMedGoogle Scholar
  23. Langdon DW, Amato MP, Boringa J, Brochet B, Foley F, Fredrikson S, Hamalainen P, Hartung HP, Krupp L, Penner IK, Reder AT, Benedict RH (2012) Recommendations for a Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS). Mult Scler 18(6):891–898PubMedCentralCrossRefPubMedGoogle Scholar
  24. McGough JJ, Biederman J, Greenhill LL, McCracken JT, Spencer TJ, Posner K, Wigal S, Gornbein J, Tulloch S, Swanson JM (2003) Pharmacokinetics of SLI381 (ADDERALL XR), an extended-release formulation of Adderall. J Am Acad Child Adolesc Psychiatry 42(6):684–691CrossRefPubMedGoogle Scholar
  25. McKeage K, Scott LJ (2003) SLI-381 (Adderall XR). CNS Drugs 17(9):669–675, discussion 676–667CrossRefPubMedGoogle Scholar
  26. Morrow SA, Kaushik T, Zarevics P, Erlanger D, Bear MF, Munschauer FE, Benedict RH (2009) The effects of L-amphetamine sulfate on cognition in MS patients: results of a randomized controlled trial. J Neurol 256(7):1095–1102CrossRefPubMedGoogle Scholar
  27. Morrow SA, O'Connor PW, Polman CH, Goodman AD, Kappos L, Lublin FD, Rudick RA, Jurgensen S, Paes D, Forrestal F, Benedict RH (2010a) Evaluation of the Symbol Digit Modalities Test (SDMT) and MS Neuropsychological Screening Questionnaire (MSNQ) in natalizumab-treated MS patients over 48 weeks. Mult Scler 16(11):1385–1392CrossRefPubMedGoogle Scholar
  28. Morrow SA, Drake A, Zivadinov R, Munschauer F, Weinstock-Guttman B, Benedict RH (2010b) Predicting loss of employment over three years in multiple sclerosis: clinically meaningful cognitive decline. Clin Neuropsychol 24(7):1131–1145CrossRefPubMedGoogle Scholar
  29. Morrow SA, Smerbeck A, Patrick K, Cookfair D, Weinstock-Guttman B, Benedict RH (2013) Lisdexamfetamine dimesylate improves processing speed and memory in cognitively impaired MS patients: a phase II study. J Neurol 260(2):489–497CrossRefPubMedGoogle Scholar
  30. Parmenter BA, Weinstock-Guttman B, Garg N, Munschauer F, Benedict RH (2007a) Screening for cognitive impairment in multiple sclerosis using the Symbol Digit Modalities Test. Mult Scler 13(1):52–57CrossRefPubMedGoogle Scholar
  31. Parmenter BA, Zivadinov R, Kerenyi L, Gavett R, Weinstock-Guttman B, Dwyer MG, Garg N, Munschauer F, Benedict RH (2007b) Validity of the Wisconsin Card Sorting and Delis-Kaplan Executive Function System (DKEFS) Sorting Tests in multiple sclerosis. J Clin Exp Neuropsychol 29(2):215–223CrossRefPubMedGoogle Scholar
  32. Pharmaceuticals S (2011) Medication guide. Highlights of prescribing information. US Drug and Food Administration, WayneGoogle Scholar
  33. Pietrzak RH, Snyder PJ, Maruff P (2010) Use of an acute challenge with d-amphetamine to model cognitive improvement in chronic schizophrenia. Hum Psychopharmacol Clin Exp 25:353–358CrossRefGoogle Scholar
  34. Rao SM (1991) A manual for the Brief Repeatable Battery of Neuropsychological Tests in multiple sclerosisGoogle Scholar
  35. Rao SM (1995) Neuropsychology of multiple sclerosis. Curr Opin Neurol 8:216–220CrossRefPubMedGoogle Scholar
  36. Rao SM, Leo GJ, Bernardin L, Unverzagt F (1991) Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction. Neurology 41(5):685–691CrossRefPubMedGoogle Scholar
  37. Rhodes SM, Coghill DR, Matthews K (2004) Methylphenidate restores visual memory, but not working memory function in attention deficit-hyperkinetic disorder. Psychopharmacology (Berlin) 175(3):319–330CrossRefGoogle Scholar
  38. Schweitzer JB, Lee DO, Hanford RB, Zink CF, Ely TD, Tagamets MA, Hoffman JM, Grafton ST, Kilts CD (2004) Effect of methylphenidate on executive functioning in adults with attention-deficit/hyperactivity disorder: normalization of behavior but not related brain activity. Biol Psychiatry 56(8):597–606CrossRefPubMedGoogle Scholar
  39. Schwid SR, Goodman AD, Weinstein A, McDermott MP, Johnson KP (2007) Cognitive function in relapsing multiple sclerosis: minimal changes in a 10-year clinical trial. J Neurol Sci 255(1–2):57–63CrossRefPubMedGoogle Scholar
  40. Smith A (1982) Symbol Digit Modalities Test: manual. Western Psychological Services, Los AngelesGoogle Scholar
  41. Solanto MV (1998) Neuropsychopharmacological mechanisms of stimulant drug action in attention-deficit hyperactivity disorder: a review and integration. Behav Brain Res 94(1):127–152CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Department of Clinical Neurological Sciences, London Health Sciences CenterWestern UniversityLondonCanada

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