Prospective, double-blind, randomized, placebo-controlled comparison of acetazolamide versus ibuprofen for prophylaxis against high altitude headache: the Headache Evaluation at Altitude Trial (HEAT).
OBJECTIVE
High altitude headache (HAH) is the most common neurological complaint at altitude and the defining component of acute mountain sickness (AMS). However, there is a paucity of literature concerning its prevention. Toward this end, we initiated a prospective, double-blind, randomized, placebo-controlled trial in the Nepal Himalaya designed to compare the effectiveness of ibuprofen and acetazolamide for the prevention of HAH.


METHODS
Three hundred forty-three healthy western trekkers were recruited at altitudes of 4280 m and 4358 m and assigned to receive ibuprofen 600 mg, acetazolamide 85 mg, or placebo 3 times daily before continued ascent to 4928 m. Outcome measures included headache incidence and severity, AMS incidence and severity on the Lake Louise AMS Questionnaire (LLQ), and visual analog scale (VAS).


RESULTS
Two hundred sixty-five of 343 subjects completed the trial. HAH incidence was similar when treated with acetazolamide (27.1%) or ibuprofen (27.5%; P = .95), and both agents were significantly more effective than placebo (45.3%; P = .01). AMS incidence was similar when treated with acetazolamide (18.8%) or ibuprofen (13.7%; P = .34), and both agents were significantly more effective than placebo (28.6%; P = .03). In fully compliant participants, moderate or severe headache incidence was similar when treated with acetazolamide (3.8%) or ibuprofen (4.7%; P = .79), and both agents were significantly more effective than placebo (13.5%; P = .03).


CONCLUSIONS
Ibuprofen and acetazolamide were similarly effective in preventing HAH. Ibuprofen was similar to acetazolamide in preventing symptoms of AMS, an interesting finding that implies a potentially new approach to prevention of cerebral forms of acute altitude illness.
Gertsch
Jeffrey H
JH
Department of Neurosciences, University of California-San Diego School of Medicine, San Diego, CA 92103-8465, USA. jgertsch@ucsd.edu
Lipman
Grant S
GS
Holck
Peter S
PS
Merritt
Andrew
A
Mulcahy
Allison
A
Fisher
Robert S
RS
Basnyat
Buddha
B
Allison
Eric
E
Hanzelka
Keeli
K
Hazan
Alberto
A
Meyers
Zachary
Z
Odegaard
Justin
J
Pook
Benjamin
B
Thompson
Mark
M
Slomovic
Brant
B
Wahlberg
Henrik
H
Wilshaw
Vanessa
V
Weiss
Eric A
EA
Zafren
Ken
K
D000086:Acetazolamide / Q000008:administration & dosage*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000532:Altitude Sickness / Q000150:complications* / Q000517:prevention & control*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D006261:Headache / Q000453:epidemiology / Q000209:etiology* / Q000517:prevention & control*; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009051:Mountaineering; D010147:Pain Measurement; D010919:Placebos; D055815:Young Adult
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010919:Placebos; D000086:Acetazolamide; D007052:Ibuprofen