title: Nocebo is the enemy, not placebo. A meta-analysis of reported side effects after placebo treatment in headaches.
abstract: The aim was to determine the magnitude of the nocebo (adverse effects following placebo administration) in clinical trials for primary headache disorders. We reviewed randomized, placebo-controlled studies for migraine, tension-type headache (TTH), and cluster headache treatments published between 1998 and 2009. The frequency of nocebo was estimated by the percentage of placebo-treated patients reporting at least one adverse side effect. The dropout frequency was estimated by the percentage of placebo-treated patients who discontinued the treatment due to intolerance. In studies of symptomatic treatment for migraine, the nocebo and dropout frequencies were 18.45% and 0.33%, but rose to 42.78% and 4.75% in preventative treatment studies. In trials for prevention of TTH, nocebo and dropout frequencies were 23.99% and 5.44%. For symptomatic treatment of cluster headache, the nocebo frequency was 18.67%. Nocebo is prevalent in clinical trials for primary headaches, particularly in preventive treatment studies. Dropouts due to nocebo effect may confound the interpretation of many clinical trials.
authors.affiliation: Neurology Department, Athens Naval Hospital, 77A Vas. Sofias Avenue, Athens, Greece. dmitsikostas@ath.forthnet.gr
authors.forename: Dimos D
authors.initials: DD
authors.lastname: Mitsikostas
authors.forename: Leonidas I
authors.initials: LI
authors.lastname: Mantonakis
authors.forename: Nikolaos G
authors.initials: NG
authors.lastname: Chalarakis
mesh_terms: D006261:Headache / Q000188:drug therapy*; D006801:Humans; D010352:Patient Dropouts / Q000523:psychology; D010919:Placebos / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic / Q000523:psychology*
chemical_list: D010919:Placebos