Published Online
on December 1, 2005

A more recent version of this article appeared on January 1, 2006

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Submitted on August 9, 2005
Revised on August 25, 2005
Accepted on September 2, 2005

Physiotherapy Coupled With Dextroamphetamine for Rehabilitation After Hemiparetic Stroke. A Randomized, Double-Blind, Placebo-Controlled Trial

David J. Gladstone BSc, MD, FRCPC^*; Cynthia J. Danells BScPT, MSc; Armi Armesto RN, BScN, MHSM; William E. McIlroy BSc, PhD; W. Richard Staines PhD; Simon J. Graham PhD, PEng; Nathan Herrmann MD, FRCPC; John P. Szalai PhD; Sandra E. Black MD, FRCPC; for the Subacute Therapy with Amphetamine and Rehabilitation for Stroke (STARS) Study Investigators

From the Regional Stroke Centre (North and East GTA-Ontario Region Stroke Network) and Division of Neurology (D.J.G., A.A., W.E.M., W.R.S., S.E.B.), Department of Medicine, and Neurosciences Research, Sunnybrook and Women’s College Health Sciences Centre, Department of Medicine, University of Toronto, Ontario, Canada; Heart and Stroke Foundation Centre for Stroke Recovery (D.J.G., C.J.D., W.E.M., W.R.S., S.J.G., S.E.B.), Canada; Graduate Department of Rehabilitation Sciences (C.J.D., W.E.M.), University of Toronto, Ontario, Canada; Department of Imaging Research, Sunnybrook and Women’s College Health Sciences Centre and Department of Medical Biophysics (S.J.G.), University of Toronto, Ontario; Department of Psychiatry (N.H.), Sunnybrook and Women’s College Health Sciences Centre, Department of Psychiatry, University of Toronto, Ontario, Canada; and Department of Biostatistics (J.P.S.), Sunnybrook and Women’s College Health Sciences Centre, University of Toronto, Ontario, Canada.

^* To whom correspondence should be addressed. E-mail: david.gladstone{at}sw.ca.

Background and Purpose--Hemiparesis is the commonest disabling deficit caused by stroke. In animals, dextroamphetamine (AMPH) paired with training enhances motor recovery, but its clinical efficacy is uncertain.

Methods--In a randomized, double-blind, placebo-controlled trial, 71 stroke patients were stratified by hemiparesis severity and randomly assigned to 10 sessions of physiotherapy coupled with either 10 mg AMPH or placebo. Study treatments were administered by 1 physiotherapist, beginning 5 to 10 days after stroke and continuing twice per week for 5 weeks. Outcomes were assessed by 1 physiotherapist at baseline, after each treatment session, at 6 weeks, and at 3 months. The primary outcome was motor recovery (impairment level) on the Fugl-Meyer (FM) scale. Secondary outcomes assessed mobility, ambulation, arm/hand function, and independence in activities of daily living.

Results--Baseline hemiparesis was severe overall (mean FM score 27.7±20.0). Motor scores improved during treatment in both groups (mean change, baseline to 3 months 29.5±16.6). Repeated-measures ANOVA revealed no significant differences in recovery between the treatment groups for the entire cohort (n=67) or for subgroups with a severe hemiparesis (n=43), moderate hemiparesis (n=24), or cortically based stroke (n=26). In the moderate subgroup, there was a significant drugxtime interaction for upper extremity motor recovery (F=5.14; P<0.001), although there was a significant baseline imbalance in motor scores in this subgroup.

Conclusion--In stroke patients with a severe motor deficit, 10 mg AMPH coupled with physiotherapy twice per week for 5 weeks in the early poststroke period provided no additional benefit in motor or functional recovery compared with physiotherapy alone. Patients with moderate severity hemiparesis deserve further investigation. Increased intensity and longer duration drug/therapy dosing regimens should be explored, targeting the upper and lower limbs separately.

Key words: amphetamines • physiotherapy • randomized controlled trials • rehabilitation

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