An Meta-analysis Of Nocebo Effect In Prophylactic Treatment Of Migraine In Clinical Trails

Objective: to quantitatively summarize adverse events reported inplacebo arm of RCTs for migraine prophylaxis.Method: We systematically searched MEDLINE and CENTRALdatabase for English-language articles of RCTs investigating antiepilepticsand beta-blockers in migraine prophylaxis of human subjects from1988to2012. Percentages of patients in placebo group reporting at least one AE ordiscontinuing due to placebo intolerance were assessed. Stratified analysiswas conducted on nocebo effect according to different factors, includingdifferent drugs, study populations, publication years and Jadad score.Result:24studies met the selection criteria, for a total of1,671patientsin placebo group were included in the meta-analysis. The mean noceboeffect frequency was38.0%(95%CI24-52.1%), ranging from6.9%to80%.For dropout because of nocebo effect, the mean frequency was2%(95%CI1.2-2.7%), ranging from0%to30%. When compared nocebo effect ofantiepileptics in RCTs with of beta blockers, it was higher in treatment ofantiepileptics (44.8%) than beta blockers (17.8%). Moreover, younger age, later publication year and higher Jadad score were associated with increasednocebo effect rate.Conclusion: Our analysis indicates nocebo was common in RCTs formigraine preventive treatments. New recruiting policies and modifiedmethodology for further study of nocebo effect and nocebo dropout shouldbe taken into account when new clinical trails are designed. Furthermore,since nocebo limits the therapeutic effects of preventive drugs in migraine,the way of releasing safety information warrants greater attention in dailypractice.