Abstract
Amphetamine enhances recovery after experimental ischaemia and has shown promise in small clinical trials when combined with motor or sensory stimulation. Amphetamine, a sympathomimetic, might have haemodynamic effects in stroke patients, although limited data have been published. Subjects were recruited 3–30 days post-ischaemic stroke into a phase II randomized (1:1), double-blind, placebo-controlled trial. Subjects received dexamphetamine (5 mg initially, then 10 mg for 10 subsequent doses with 3- or 4-day separations) or placebo in addition to inpatient physiotherapy. Recovery was assessed by motor scales (Fugl–Meyer (FM)), and functional scales (Barthel index (BI) and modified Rankin score (mRS)). Peripheral blood pressure (BP), central haemodynamics and middle cerebral artery blood flow velocity were assessed before, and 90 min after, the first two doses. Thirty-three subjects were recruited, aged 33–88 (mean 71) years, males 52%, 4–30 (median 15) days post stroke to inclusion. Sixteen patients were randomized to placebo and seventeen to amphetamine. Amphetamine did not improve motor function at 90 days; mean (s.d.) FM 37.6 (27.6) vs control 35.2 (27.8) (P=0.81). Functional outcome (BI, mRS) did not differ between treatment groups. Peripheral and central systolic BP, and heart rate (HR), were 11.2 mm Hg (P=0.03), 9.5 mm Hg (P=0.04) and 7 beats per minute (P=0.02) higher, respectively, with amphetamine, compared with control. A nonsignificant reduction in myocardial perfusion (BUI) was seen with amphetamine. Other cardiac and cerebral haemodynamics were unaffected. Amphetamine did not improve motor impairment or function after ischaemic stroke but did significantly increase BP and HR without altering cerebral haemodynamics.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 digital issues and online access to articles
$119.00 per year
only $9.92 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Johannson B . Brain plasticity and stroke rehabilitation; the Willis Lecture. Stroke 2000; 31: 223.
Meairs S, Wahlgren N, Dirnagl U, Lindvall O, Rothwell P, Baron J-C et al. Stroke research priorities for the next decade – a representative view of the European scientific community. Cerebrovasc Dis 2006; 22: 75–82.
Sprigg N, Bath PMW . Pharmacological enhancement of recovery from stroke. Current Medical Literature: Stroke Review 2005; 8: 33–39.
Philips JP, Devier DJ, Feeney DM . Rehabilitation pharmacology: bridging laboratory work to clinical application. J Head Trauma Rehabil 2003; 18: 342–356.
Feeney DM, Gonzalez A, Law WA . Amphetamine, haloperidol, and experience interact to affect rate of recovery after motor cortex injury. Science 1982; 217: 855–857.
Goldstein L . Potential effects of common drugs on stroke recovery. Arch Neurol 1999; 55: 454–456.
Gladstone DG, Black SE . Enhancing recovery after stroke with noradrenergic pharmacotherapy: a new frontier? Can J Neurol Sci 2000; 27: 97–105.
Ziemann U, Meintzchel F, Korchounov A, Ilic T . Pharmacological modulation of plasticity in the human motor cortex. Neurorehabil Neural Repair 2006; 20: 243–251.
Hurwitz BE, Dietrich WD, McCabe PM, Alonso O, Watson BD, Ginsberg MD et al. Amphetamine promotes recovery from sensory-motor integration deficit after thrombotic infarction of the primary somatosensory rat cortex. Stroke 1991; 22: 648–654.
Barbay S, Zoubina EV, Dancause N, Frost SB, Eisner-Janowicz I, Stowe AM et al. A single injection of D-amphetamine facilitates improvements in motor training following a focal cortical infarct in squirrel monkeys. Neurorehabil Neural Repair 2006; 20: 455–458.
Brown AW, Bjelke B, Fuxe K . Motor response to amphetamine treatment, task-specific training, and limited motor experience in a postacute animal stroke model. Exp Neurol 2004; 190: 102–108.
Wang Y, Hayashi T, Chang C-F, Chiang Y-H, Tsao L-I, Su T-P et al. Methamphetamine potentiates ischemia/reperfusion insults after transient middle cerebral artery ligation. Stroke 2001; 32: 775–782.
Knecht S, Imai T, Kamping S, Breitenstein C, Henningsen H, Lutkenhoner B et al. -Amphetamine does not improve outcome of somatosensory training. Neurology 2001; 57: 2248–2252.
Nitsche M, Grundey J, Liebetanz D, Lang N, Tergau F, Paulus W . Catecholaminergic consolidation of motor cortex neuroplasticity in humans. Cereb Cortex 2004; 14: 1240–1245.
Meintzschel F, Ziemann U . Modifications of practice-dependent plasticity in human motor cortex by neuromodulators. Cereb Cortex 2006; 16: 1106–1115.
Crisostomo EA, Duncan PW, Propst M, Dawson DV, Davis JN . Evidence that amphetamine with physical therapy promotes recovery of motor function in stroke patients. Ann Neurol 1988; 23: 94–97.
Walker-Batson D, Smith P, Curtis S, Unwin H, Greenlee R . Amphetamine paired with physical therapy accelerates motor recovery after stroke. Stroke 1995; 26: 2254–2259.
Reding MJ, Solomon B, Borucki S . Effect of dextroamphetamine on motor recovery after stroke. Neurology 1995; 45 (Suppl 4): a222.
Mazagri R, Shuaib A, McPherson M, Deighton M . Amphetamine failed to improve motor function in acute stroke (abstract). Can J Neurol Sci 1995; 22 (2) (Suppl 1): S25.
Vachalathiti R, Asavavallobh C, Nilanont Y, Poungvarin N . Comparison of physical therapy and physical therapy with amphetamines in sensorimotor recovery of acute stroke patients: randomised control. J Neurol Sci 2001; 187: S253 (Abst. P0724).
Treig T, Werner C, Sachse M, Hesse S . No benefit from D-amphetamine when added to physiotherapy after stroke: a randomised placebo-controlled study. Clin Rehabil 2003; 17: 590–599.
Martinsson L, Wahlgrew NG, Hardemark H . Safety of dexamphetamine in acute ischaemic stroke-randomized double-blind controlled dose escalation trial. Stroke 2003; 34: 475–481.
Sonde L, Nordstrom M, Nilsson CG, Lokk J . A double-blind placebo-controlled study of the effects of amphetamine and physiotherapy after stroke. Cerebrovasc Dis 2001; 12: 253–257.
Gladstone DJ, Danells CJ, Armesto A, McIlroy WE, Staines WR, Graham SJ et al. Physiotherapy coupled with dextroamphetamine for rehabilitation after hemiparetic stroke. Stroke 2006; 37: 179–185.
Grade C, Redford B, Chrostowski J . Methylphenidate in early poststroke recovery: a double-blind, placebo-controlled study. Arch Phys Med Rehabil 1998; 79: 1047–1050.
Platz T, Kim IH, Engel U, Pinkowski C, Eickhof C, Kutzner M . Amphetamine fails to facilitate motor performance and to enhance motor recovery among stroke patients with mild arm paresis: Interim analysis and termination of a double blind, randomised, placebo-controlled trial. Restor Neurol Neurosci 2005; 23: 271–280.
Sonde L, Lokk J . Effects of amphetamine and/or L-dopa and physiotherapy after stroke – a blinded randomized study. Acta Neurol Scand 2007; 115: 55–59.
Martinsson L, Wahlgren NG, Hårdemark H-G . Amphetamines for improving recovery after stroke (Cochrane review). The Cochrane Library 2003, Issue 3. John Wiley and Sons, Ltd.
British National Formulary. http://bnf.org/bnf/index.htm, 2006.
Martinsson L, Wahlgren NG . Safety of dexamphetamine in acute ischaemic stroke-randomized double-blind controlled dose escalation trial. Stroke 2003; 34: 475–481.
Prospective Studies Collaboration. Age specific relevance of usual blood pressure to vascular mortality: a meta analysis of individual data for one million adults in 61 prospective studies. Lancet 2002; 360: 1903–1913.
Leonardi-Bee J, Bath PM, Bousser MG, Davalos A, Diener H-C, Guiraud-Chaumeil B et al. Dipyridamole for preventing recurrent ischaemic stroke and other vascular events: a meta-analysis of individual patient data from randomized controlled trials. Stroke 2005; 36: 162–168.
Carey LM, Abbott DF, Egan GF, Bernhardt J, Donnan GA . Motor impairment and recovery in the upper limb after stroke: behavioural and neuroanatomical correlates. Stroke 2005; 36: 625–629.
Sprigg N, Gray LJ, Bath PMW . Relationship between functional outcome and baseline blood pressure, pulse pressure and heart rate in acute ischaemic stroke: data from the TAIST trial. J Hypertens 2006; 24: 1413–1417.
Walker-Batson D . A double-blind placebo-controlled study of the use of amphetamine in the treatment of aphasia. Stroke 2001; 32: 2093–2098.
Treig T, Werner C, Sachse M, Hesse S . No benefit from D-amphetamine when added to physiotherapy after stroke: a randomised placebo-controlled study. Clin Rehabil 2003; 17: 590–599.
Sprigg N, Gray LJ, Bath PMW, Sorensen P, Lindenstrom E, Boysen G et al. Relationship between functional outcome and baseline blood pressure, pulse pressure and heart rate in acute ischaemic stroke: data from the TAIST trial. J Hypertens 2006; 24: 1413–1417.
Buckberg GD . Subendocardial ischaemia after cardiopulmonary bypass. J Thorac Cardiovasc Surg 1972; 64: 669–684.
Hennerici M, Rautenberg W, Sitzer G, Schwartz A . Transcranial doppler for the assessment of intracranial arterial flow velocity – part 1. Surg Neurol 1987; 27: 439–448.
Hancock S, Eastwood J, Mahajan R . Effects of inhaled nitrous oxide 50% on estimated cerebral perfusion pressure and zero flow pressure in healthy volunteers. Anaesthesia 2005; 60: 129–132.
Athanassiou L, Hancock S, Mahajan R . Doppler estimation of zero flow pressure during changes in downstream pressure in a bench model of a circulation using pulsatile flow. Anaesthesia 2005; 60: 133–138.
McEvoy AW, Kitchen ND, Thomas DGT . Intracerebral haemorrhage in young adults: the emerging importance of drug misuse. Br Med J 2000; 320: 1322–1324.
O’Rourke MF, Adji A . An updated clinical primer on large artery mechanics: implications of pulse waveform analysis and arterial tonometry. Curr Opin Cardiol 2005; 20: 275–281.
Robinson BF . Relation of heart rate and systolic blood pressure to the onset of pain in angina pectoris. Circulation 1967; 35: 1073–1083.
Devous MD, Madhukar H, Trivedi MH, Rush AJ . Regional cerebral blood flow response to oral amphetamine challenge in healthy volunteers. J Nucl Med 2001; 42: 535–542.
LaRue LJ, Alter M, Traaven ND, Sterman AB, Sobel E, Kleiner J . Acute stroke therapy trials: problems in patient accrual. Stroke 1988; 19: 950–954.
Stroemer RP, Kent TA, Hulsebosch CE . Enhanced neocortical neural sprouting, synaptogenesis, and behavioural recovery with D-amphetamine therapy after neocortical infarction in rats. Stroke 1998; 29: 2381–2393; discussion 2393–2385.
Hovda DA, Fenney DM . Amphetamine with experience promotes recovery of locomotor function after unilateral frontal cortex injury in the cat. Brain Res 1984; 298: 358–361.
Butefisch CM, Davis BC, Sawaki L, Waldvogel D, Classen J, Kopylev L et al. Modulation of use-dependent plasticity by D-amphetamine. Ann Neurol 2002; 51: 59–68.
Bamford J, Sandercock P, Dennis M, Burn J, Warlow C . Classification and natural history of clinically identifiable subtypes of cerebral infarction. Lancet 1991; 337: 1521–1526.
Adams HP, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL et al. Classification of subtype of acute ischaemic stroke. Definitions for use in a multicenter clinical trial. Stroke 1993; 24: 35–41.
Acknowledgements
We thank therapists Helen Hill, Christine Walker, Louise Connell and Jeremy Newton for performing outcome assessments. PB, MW, VP and AS conceived, designed and supervised the study; MRW and NS recruited patients and performed systemic and cerebral haemodynamic studies; NS and LG performed the statistical analyses; NS and PB wrote the first draft of this paper, all the other authors commented on and approved the final draft; PB is the study guarantor. Support was received from BUPA Foundation (NS, LG) and The Hypertension Trust (MRW). PB is Stroke Association Professor of Stroke Medicine.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sprigg, N., Willmot, M., Gray, L. et al. Amphetamine increases blood pressure and heart rate but has no effect on motor recovery or cerebral haemodynamics in ischaemic stroke: a randomized controlled trial (ISRCTN 36285333). J Hum Hypertens 21, 616–624 (2007). https://doi.org/10.1038/sj.jhh.1002205
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.jhh.1002205
Keywords
This article is cited by
-
Obesity Management in Cardiometabolic Disease: State of the Art
Current Atherosclerosis Reports (2021)
-
Central Noradrenergic Agonists in the Treatment of Ischemic Stroke—an Overview
Translational Stroke Research (2020)
-
Effects of Central Nervous System Drugs on Recovery After Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Clinical Drug Investigation (2017)
-
Investigation of the mechanisms mediating MDMA “Ecstasy”-induced increases in cerebro-cortical perfusion determined by btASL MRI
Psychopharmacology (2015)
-
Toxicity of amphetamines: an update
Archives of Toxicology (2012)