Lubiprostone use heightens risk of headache

Treatment with lubiprostone is associated with an increased risk of headache in adults and children, according to a recent meta-analysis.

Twenty-six studies met the eligibility criteria for this study. The incidence of headache was 5.3 percent with lubiprostone and 3.2 percent with placebo or other laxatives.

The use of lubiprostone resulted in a higher risk of headache (risk ratio [RR], 1.32, 95 percent confidence interval [CI], 1.02–1.71; I2, 0 percent; n=6,265 patients; 26 randomized controlled trials [RCTs]; moderate certainty) than placebo or other laxatives.

Furthermore, the increased risk of headache was consistent in both adults (RR, 1.23, 95 percent CI, 0.93–1.62; I2, 0 percent; n=5,390; 24 RCTs; moderate certainty) and children (RR, 3.07, 95 percent CI, 1.67–5.63; I2, 84.4 percent; n=875 patients; two RCTs; very low certainty).

In this study, the investigators searched Medline (via PubMed), clinicaltrials.gov, and the Cochrane Central Register of Controlled Trials for all relevant RCTs. Studies were included if they compared lubiprostone with placebo or other laxatives.

RRs and 95 percent CIs were estimated using a DerSimonian–Laird random-effects model. A fixed-effect method based on the Mantel–Haenszel method was used for analyses with three or fewer studies. Finally, the investigators assessed heterogeneity using the I2 statistic and rated the certainty of evidence using the GRADE approach.

“Lubiprostone and its active metabolite may activate prostaglandin receptors, raising concerns about an increased risk of headache,” the investigators said.