Efficacy of ibuprofen on prevention of high altitude headache: A systematic review and meta-analysis

Objective: Ibuprofen is used to prevent high altitude headache (HAH) but its efficacy remains controversial. We conducted a systematic review and meta-analysis of randomized, placebo-controlled trials (RCTs) of ibuprofen for the prevention of HAH. Methods: Studies reporting efficacy of ibuprofen for prevention of HAH were identified by searching electronic databases (until December 2016). The primary outcome was the difference in incidence of HAH between ibuprofen and placebo groups. Risk ratios (RR) were aggregated using a Mantel-Haenszel random effect model. Heterogeneity of included trials was assessed using the I2 statistics. Results: In three randomized-controlled clinical trials involving 407 subjects, HAH occurred in 101 of 239 subjects (42%) who received ibuprofen and 96 of 168 (57%) who received placebo (RR = 0.79, 95% CI 0.66 to 0.96, Z = 2.43, P = 0.02, I2 = 0%). The absolute risk reduction (ARR) was 15%. Number needed to treat (NNT) to prevent HAH was 7. Similarly, The incidence of severe HAH was significant in the two groups (RR = 0.40, 95% CI 0.17 to 0.93, Z = 2.14, P = 0.03, I2 = 0%). Severe HAH occurred in 3% treated with ibuprofen and 10% with placebo. The ARR was 8%. NNT to prevent severe HAH was 13. Headache severity using a visual analogue scale was not different between ibuprofen and placebo. Similarly, the difference between the two groups in the change in SpO2 from baseline to altitude was not different. One included RCT reported one participant with black stools and three participants with stomach pain in the ibuprofen group, while seven participants reported stomach pain in the placebo group. Conclusions: Based on a limited number of studies ibuprofen seems efficacious for the prevention of HAH and may therefore represent an alternative for preventing HAH with acetazolamide or dexamethasone.