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)

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 ¼ 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 ¼ 0.03), 9.5 mm Hg (P ¼ 0.04) and 7 beats per minute (P ¼ 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.

Stroke, with or with no ice? Observations on amphetamine for the management of acute stroke

“…22 While these observations suggest that stroke patients with mild motor deficits are more responsive to D-amphetamine effects, another clinical study proved this hypothesis wrong, in that the trial was halted when the interim efficacy analysis of 26 stroke patients with mild arm paresis revealed lack of motor facilitation or motor recovery with D-amphetamine over placebo at immediate post-training or long-term periods. 23 In this issue of the Journal of Human Hypertension, the new study Bath et al 24 corroborates recent reports that amphetamine has limited therapeutic effects for improving stroke outcome. Here, the authors report that amphetamine does not improve motor function, but increases blood pressure and heart rate.…”

A speedy recovery: amphetamines and other therapeutics that might impact the recovery from brain injury

“…The best management concerning various critical variables (type of cerebral lesion, lack of comorbidity, age of animals, exact schedule of amphetamine treatment and combination with targeted physical training) remains unclear as they are carried out in different ways in studies in animals as well as in humans [28,29]. These factors are of clinical relevance [6] as the quality of postinjury experience is crucial to the rate and extent of recovery [30 ].…”

Speeding stroke recovery?

“…17,18,20 Systolic and diastolic blood pressure both showed significant increases after dexamphetamine, WMD 9.29 (95% CI, 3.26 to 15.32) (figure 5) and WMD 5.13 (95% CI, 1.61 to 8.64) respectively. Heart rate was also significantly increased with amphetamine, WMD 7.61 (95% CI 1.78 to 13.43) (figure 6).…”

“…Neurological impairment was assessed in 2 studies (n=67 patients); 17,18 there were trends to better neurological score (SSS), WMD 2.43 (95% CI, -4.41 to 9.28), and greater change in score between baseline and end-of-treatment, WMD 3.96 (95% CI, -1.23 to 9.15) in the amphetamine group ( figure 9). …”