Altitude Sickness Prevention with Ibuprofen Relative to Acetazolamide

Am J Med. 2019 Feb;132(2):247-251. doi: 10.1016/j.amjmed.2018.10.021. Epub 2018 Nov 10.


Background: Acute mountain sickness is a common occurrence for travel to high altitudes. Although previous studies of ibuprofen have shown efficacy for the prevention of acute mountain sickness, recommendations have been limited, as ibuprofen has not been compared directly with acetazolamide until this study.

Methods: Before their ascent to 3810 m on White Mountain in California, adult volunteers were randomized to ibuprofen (600 mg, 3 times daily, started 4 hours before the ascent), or to acetazolamide (125 mg, twice daily, started the night before the ascent). The main outcome measure was acute mountain sickness incidence, using the Lake Louise Questionnaire (LLQ), with a score of >3 with headache. Sleep quality and headache severity were measured with the Groningen Sleep Quality Survey (GSQS). This trial was registered at NCT03154645 RESULTS: Ninety-two participants completed the study: 45 (49%) on ibuprofen and 47 (51%) on acetazolamide. The total incidence of acute mountain sickness was 56.5%, with the incidence for the ibuprofen group being 11% greater than that for acetazolamide, surpassing the predetermined 26% noninferiority margin (62.2% vs 51.1%; 95% confidence interval [CI], -11.1 to 33.5). No difference was found in the total LLQ scores or subgroup symptoms between drugs (P = .8). The GSQS correlated with LLQ sleep (r = 0.77; 95% CI, 0.67-0.84)=%. The acetazolamide group had higher peripheral capillary oxygen saturation than the ibuprofen group (88.5% vs 85.6%; P = .001).

Conclusion: Ibuprofen was slightly inferior to acetazolamide for acute mountain sickness prevention and should not be recommended over acetazolamide for rapid ascent. Average symptoms and severity were similar between drugs, suggesting prevention of disease.

Keywords: Acetazolamide; Acute mountain sickness; Altitude; Altitude medicine; Ibuprofen.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetazolamide / therapeutic use*
  • Adult
  • Altitude Sickness / prevention & control*
  • California
  • Carbonic Anhydrase Inhibitors / therapeutic use
  • Cyclooxygenase Inhibitors / therapeutic use
  • Double-Blind Method
  • Female
  • Humans
  • Ibuprofen / therapeutic use*
  • Male
  • Severity of Illness Index
  • Surveys and Questionnaires


  • Carbonic Anhydrase Inhibitors
  • Cyclooxygenase Inhibitors
  • Acetazolamide
  • Ibuprofen

Associated data