Safety of dexamphetamine in acute ischemic stroke: a randomized, double-blind, controlled dose-escalation trial.
OBJECTIVE
Amphetamine is reported to enhance recovery after experimental stroke, but results from the first few trials in humans are inconclusive. Limited information is available on treatment safety. This study intended to investigate the safety and tolerability of dexamphetamine in patients with acute cerebral ischemia.


METHODS
Forty-five patients with cerebral ischemia were enrolled within 72 hours after onset of symptoms. Patients were randomized to 1 of 3 dose levels (2.5, 5, or 10 mg orally twice daily) or placebo for 5 consecutive days. Adverse events, blood pressure, heart rate, body temperature, consciousness level, and functional outcome measures were followed up daily during treatment. Follow-ups were made at day 7 and 1 and 3 months after stroke.


RESULTS
Mean systolic and diastolic blood pressures and heart rate increased 14 mm Hg, 8 mm Hg, and 9 bpm, respectively, with dexamphetamine treatment compared with placebo (P< or =0.01). There was no difference between dexamphetamine and placebo regarding adverse events, body temperature, or consciousness level. During treatment, there was a benefit of dexamphetamine in neurological and functional outcome (P<0.05), but differences were not maintained at follow-up.


CONCLUSIONS
Overall, dexamphetamine was safe and well tolerated by patients with acute cerebral ischemia, but blood pressure and heart rate increased during treatment in comparison to placebo. These observations may be important in the future planning of amphetamine trials because changes in these variables have been observed to interfere with clinical outcome. The suggestions of improvement in outcome must be confirmed in further studies.
Martinsson
Louise
L
Institution of Clinical Neurosciences, Karolinska Institute, Stockholm, Sweden. louise.martinsson@ks.se
Wahlgren
Nils Gunnar
NG
D000208:Acute Disease; D000284:Administration, Oral; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy*; D003243:Consciousness / Q000187:drug effects; D003913:Dextroamphetamine / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004341:Drug Evaluation; D005260:Female; D005500:Follow-Up Studies; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020521:Stroke / Q000150:complications / Q000188:drug therapy*; D016896:Treatment Outcome
D003913:Dextroamphetamine