title: Catechol-O-methyltransferase val158met polymorphism predicts placebo effect in irritable bowel syndrome.
abstract: Identifying patients who are potential placebo responders has major implications for clinical practice and trial design. Catechol-O-methyltransferase (COMT), an important enzyme in dopamine catabolism plays a key role in processes associated with the placebo effect such as reward, pain, memory and learning. We hypothesized that the COMT functional val158met polymorphism, was a predictor of placebo effects and tested our hypothesis in a subset of 104 patients from a previously reported randomized controlled trial in irritable bowel syndrome (IBS). The three treatment arms from this study were: no-treatment ("waitlist"), placebo treatment alone ("limited") and, placebo treatment "augmented" with a supportive patient-health care provider interaction. The primary outcome measure was change from baseline in IBS-Symptom Severity Scale (IBS-SSS) after three weeks of treatment. In a regression model, the number of methionine alleles in COMT val158met was linearly related to placebo response as measured by changes in IBS-SSS (p = .035). The strongest placebo response occurred in met/met homozygotes treated in the augmented placebo arm. A smaller met/met associated effect was observed with limited placebo treatment and there was no effect in the waitlist control. These data support our hypothesis that the COMT val158met polymorphism is a potential biomarker of placebo response.
authors.affiliation: Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, United States of America. kthall@bidmc.harvard.edu
authors.forename: Kathryn T
authors.initials: KT
authors.lastname: Hall
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Lembo
authors.forename: Irving
authors.initials: I
authors.lastname: Kirsch
authors.forename: Dimitrios C
authors.initials: DC
authors.lastname: Ziogas
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Douaiher
authors.forename: Karin B
authors.initials: KB
authors.lastname: Jensen
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Conboy
authors.forename: John M
authors.initials: JM
authors.lastname: Kelley
authors.forename: Efi
authors.initials: E
authors.lastname: Kokkotou
authors.forename: Ted J
authors.initials: TJ
authors.lastname: Kaptchuk
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015990:Placebo Effect; D010919:Placebos; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D010919:Placebos; D002394:Catechol O-Methyltransferase