Catechol-O-Methyltransferase (COMT) Gene Variants Predict Response to Bupropion Therapy for Tobacco Dependence

Wade H. Berrettini, E. Paul Wileyto, Leonard Epstein, Stephanie Restine, Larry Hawk, Peter Shields, Ray Niaura, Caryn Lerman

Research output: Contribution to journalArticle


Background: Although bupropion is efficacious for smoking cessation, only a minority of smokers are able to quit. Pharmacogenetic research may improve treatment outcomes through discovery of DNA sequences predictive of successful pharmacotherapy for subgroups of smokers. We investigated variants in the catechol-O-methyltransferase (COMT) gene in a smoking cessation trial of bupropion. Methods: A double-blind, placebo-controlled, 10-week trial of bupropion and counseling (with a 6-month follow-up period) was conducted at two university-based smoking cessation research programs. Abstinence was biochemically verified at the end of treatment and at 6 months after the target quit date. Results: At the end of the treatment phase, statistically significant interaction effects indicated that COMT haplotypes of two SNPs (rs737865 and rs165599) predicted the efficacy of bupropion compared with placebo. This interaction effect was attenuated at 6-month follow-up. Conclusions: COMT haplotypes at rs737865 and rs165599 may predict a favorable outcome for bupropion treatment for smoking cessation. European-American smokers with a G allele at both SNPs may not benefit from bupropion treatment. Small numbers of some COMT haplotypes limit interpretation of response. If study findings are confirmed in additional large studies, COMT genotyping could be applied to identify likely responders to bupropion treatment for smoking cessation.

Original languageEnglish (US)
Pages (from-to)111-118
Number of pages8
JournalBiological Psychiatry
Issue number1
StatePublished - Jan 1 2007


  • COMT
  • Pharmacogenetics
  • dopamine
  • nicotine dependence
  • smoking

ASJC Scopus subject areas

  • Biological Psychiatry

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