Should Amphetamines Be Given to Improve Recovery After Stroke?
Graeme J. Hankey MD, FRCP Section Editor:
Clinical trials of pharmacological agents in stroke have mainly focused on the very acute stage, eg, using thrombolytic or neuroprotective therapy. Thrombolytic therapy is, however, only effective within the first few hours of stroke onset and so far, no neuroprotective therapy has proven to be efficacious in humans. Thus, there is a great need for new pharmacological strategies to improve outcome after stroke. Experimental animal studies suggest that treatment with amphetamines improves recovery after focal cerebral ischemia. A similar effect in humans could have a major impact on recovery from stroke.
The purpose of this study was to assess the safety and efficacy of amphetamine treatment in patients with stroke.
We searched the Cochrane Stroke Group Trials Register (last searched January 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2006), MEDLINE (1966 to January 2006), EMBASE (1980 to January 2006), CINAHL (1982 to January 2006), Science Citation Index (1992 to March 2005), and registers of ongoing trials. We also checked the reference lists of all relevant articles and reviews, websites of ongoing trials, and contacted researchers in the field.
All unconfounded randomized trials comparing amphetamine with placebo or open control were included if they evaluated the effect on outcome after stroke.
Data Collection and Analysis
Two review authors independently selected trials for inclusion and assessed trial quality; one extracted the data.
Ten studies involving 287 patients were included, but not all trials contributed data to each outcome examined in this review. The quality of the trials varied but was generally high. There was no evidence that amphetamine treatment reduced death or dependence (Peto odds ratio [Peto OR] 1.5, 95% confidence interval [CI] 0.6 to 3.3; Figure 1). Imbalances at baseline with more serious stroke allocated to amphetamine may account for the trend for more deaths at the end of follow up among amphetamine-allocated patients (Peto OR 2.8, 95% CI 0.9 to 8.6). Systolic (weighted mean difference [WMD] 8.4 mm Hg, 95% CI 1.6 to 15.2) and diastolic (WMD 4.9 mm Hg, 95% CI 1.1 to 8.8) blood pressure, as well as heart rate, increased (WMD 10.6 bpm, 95% CI 3.3 to 17.8) in amphetamine-allocated patients. There was evidence of a relative improvement from baseline to last follow-up in motor function (WMD −6.1 points; 95% CI −10.4 to −1.9; Figure 2). Different results with different analysis approaches emphasize caution in the interpretation of the results.
Implications for Clinical Practice and Future Research
Based on the present evidence, there is no indication for the routine use of amphetamines to improve recovery after stroke, but further research in this area is justified considering the possible positive effect on motor recovery. Further trials should be balanced for important prognostic factors, evaluating the long-term effects of amphetamine on substantive outcomes and a broad range of outcome variables, especially motor and language functions.
It is not possible to give the full detail of analyses on the 29 outcomes studied in this brief summary. Full details and all the graphical plots are available in the version of this review published in the Cochrane Library.1
- Received February 8, 2007.
- Revision received March 21, 2007.
- Accepted March 25, 2007.
Martinsson L, Hårdemark HG, Eksborg S. Amphetamines for improving recovery after stroke (Cochrane systematic review). In: Cochrane Database Syst Rev. 2007 Jan 24; (1): CD002090.