Sumatriptan for Prevention of Acute Mountain Sickness: Randomized Clinical Trial Sirous Jafarian, MD, Farzam Gorouhi, MD, Shabnam Salimi, MD, and Jamshid Lotfi, MD, FRCP Objective: To determine the impact of sumatriptan prophylaxis on acute mountain sickness (AMS) and altitude headache development within 24 hours of ascent, we designed a double-blind, randomized, clinical trial. Methods: A prospective, double-blind, randomized, placebo-controlled trial was conducted in Tochal Mountain Hotel at an altitude of 3,500 meters above sea level during October 2006 to November 2006. A total of 102 Iranian adults were assigned to receive either sumatriptan succinate (50mg) or placebo within 1 hour of ascent. AMS incidence was measured by Lake Louise AMS score  3 with headache and one other symptom. Secondary outcome measures included severity of syndrome (Lake Louise scores  5), incidence of headache, and severity of headache. Results: Based on intention-to-treat analysis, AMS was more prevalent in placebo group (n = 23 [45.1%]) than sumatriptan group (n = 12 [23.5%]; p = 0.02). Headache also had a greater rate for placebo users (placebo vs sumatriptan group: 29 [56.9%] vs 17 [33.3%]; p = 0.02). No association was detected between sumatriptan prophylaxis and AMS or altitude headache severity. Discussion: Sumatriptan prophylaxis is effective to prevent AMS development. Furthermore, our findings confirm cerebral vasodilative and edematous mechanisms of AMS progression, whereas sumatriptan is a selective 5-hydroxytryptamine 1 receptor subtype agonist and a selective cerebral vasoconstrictor as a result (http://www.controlled-trials.com/ISRCTN87201238/). Ann Neurol 2007;62:273–277 The term high-altitude illness is used to describe the cerebral syndromes including acute mountain sickness (AMS), high-altitude cerebral edema, and pulmonary syndromes that can develop in unacclimatized persons shortly after ascent to high altitude. 1 High-altitude ill- ness is much more likely to occur at altitudes higher than 2,500m than at lower altitudes. 2 Every year thousands of people who live at low alti- tudes climb or work in high-altitude areas; many of them experience AMS. The most common symptoms (headache, loss of appetite, nausea, fatigue, dizziness, and insomnia) usually appear within the first days of arrival at high altitude. 1–3 AMS is not only uncomfort- able, it is also partly responsible for an increased mor- tality at high altitude. 1,2 Many drugs have been used to try to prevent or al- leviate symptoms of the sickness. Prophylaxis with ac- etazolamide, dexamethasone, nifedipine, ginkgo biloba, and aspirin have shown significant improvement com- pared with placebo in prevention of AMS. 4 Why alti- tude cerebral syndromes are developed is not fully un- derstood, but brain edema and cerebral vasodilation caused by impaired autoregulation have been suggested to be the possible causes. 2 Sumatriptan is a selective 5-hydroxytryptamine 1 (5-HT 1 ) receptor subtype ago- nist and a selective cerebral vasoconstrictor that is spe- cifically effective for treatment of migraine. 5 We conducted a randomized, placebo-controlled, double-blind trial to evaluate the efficacy and safety of sumatriptan in prevention of AMS according to the principles of Good Clinical Practice. Subjects and Methods Subjects A randomized, placebo-controlled, double-blind trial was conducted on a cohort of eligible adults in Tochal Mountain Hotel clinic, Tehran, Iran, from October 1 to November 17, 2006. Tochal Hotel is located at an altitude of 3,500m above sea level next to a ski area. Individuals were transferred from a height of 1,600 to 3,500m within 45 to 60 minutes using cable cars. Temperature was 18 to 30°C (metric mea- surement) in different spots of the hotel within the days of the study performance. Participants were included if they were unacclimatized, 18 From the Department of Neurology, Shariati Hospital, Tehran Uni- versity of Medical Sciences, and Iranian Center of Neurological Sci- ences, Medical Sciences—University of Tehran, Tehran, Iran. Received Jan 6, 2007, and in revised form Mar 9. Accepted for publication Apr 26, 2007. Published online June 7, 2007, in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/ana.21162 Address correspondence to Dr Jafarian, Department of Neurology, Tehran University of Medical Sciences (TUMS), Shariati Hospital, North Kargar Street, Tehran, Iran. E-mail: jafarian_s@yahoo.com © 2007 American Neurological Association 273 Published by Wiley-Liss, Inc., through Wiley Subscription Services