Association between use of lubiprostone and headache: A systematic review and meta-analysis of randomized controlled trials.

Aims: Lubiprostone and its active metabolite may activate prostaglandin receptors, raising concerns about an increased risk of headache. We performed a systematic review and meta-analysis to identify whether lubiprostone increases the risk of headache.

Methods: To identify all relevant randomized controlled trials (RCTs), we comprehensively searched MEDLINE (via PubMed), ClinicalTrials.gov website and the Cochrane Central Register of Controlled Trials. The search focused on studies comparing lubiprostone vs. placebo or other laxatives. A DerSimonian-Laird random-effects model was utilized to estimate risk ratios (RRs) and 95% confidence intervals (CIs). A fixed-effect method based on the Mantel-Haenszel method was employed for analyses with 3 or fewer studies. Heterogeneity was assessed using the I² statistic, and the certainty of evidence was rated using the GRADE approach.

Results: Twenty-six studies were examined in the analysis. The incidence of headache was 5.3% for lubiprostone and 3.2% for placebo or other laxatives. Lubiprostone increased the risk of headache (RR 1.32, 95% CI 1.02-1.71, I² = 0%, 6265 patients, 26 RCTs, moderate certainty) relative to placebo or other laxatives. The risk of headache seemed to be consistently increased in both adults (RR 1.23, 95% CI 0.93-1.62, I² = 0%, 5390 patients, 24 RCTs, moderate certainty) and children (RR 3.07, 95% CI 1.67-5.63, I² = 84.4%, 875 patients, 2 RCTs, very low certainty).

Conclusion: The results of this meta-analysis suggest that lubiprostone treatment increases the risk of headache in adults.