title: Does the DRD2-Taq1 A polymorphism influence treatment response to bupropion hydrochloride for reduction of the nicotine withdrawal syndrome?
abstract: Bupropion hydrochloride is effective in promoting long-term abstinence from smoking and may reduce risk for relapse through attenuation of withdrawal symptoms and craving. Bupropion is a weak dopamine reuptake inhibitor, and individual genetic variation in the dopamine D2 receptor has been associated with nicotine dependence in case-control studies. Thirty smokers were randomly assigned to bupropion or placebo and interviewed using the Minnesota Nicotine Withdrawal Scale on two occasions: prior to starting medication and after 14 days on bupropion or placebo. The individual symptoms of craving, irritability, and anxiety were significantly reduced in the bupropion group, whereas no withdrawal symptoms were diminished in the placebo group. Within the bupropion group, subgroup analyses with stratification by genotype demonstrated that craving, irritability, and anxiety were significantly attenuated only among subjects with DRD2-Taq1 A2/A2 genotypes. In the DRD2-Taq1 A1/A1 and A1/A2 groups, no significant reduction was seen in any individual symptom of the nicotine withdrawal syndrome. These data suggest that bupropion attenuates specific symptoms of the nicotine withdrawal syndrome and that this effect may be modified by genotype for the dopamine D2 receptor.
authors.affiliation: Center for Primary Care and Prevention, Brown University Medical School, Providence, RI 02860, USA. sean_david@brown.edu
authors.forename: Sean P
authors.initials: SP
authors.lastname: David
authors.forename: Raymond
authors.initials: R
authors.lastname: Niaura
authors.forename: George D
authors.initials: GD
authors.lastname: Papandonatos
authors.forename: William G
authors.initials: WG
authors.lastname: Shadel
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Burkholder
authors.forename: Dana M
authors.initials: DM
authors.lastname: Britt
authors.forename: Amy
authors.initials: A
authors.lastname: Day
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Stumpff
authors.forename: Kent
authors.initials: K
authors.lastname: Hutchison
authors.forename: Michael
authors.initials: M
authors.lastname: Murphy
authors.forename: Elaine
authors.initials: E
authors.lastname: Johnstone
authors.forename: Siân-Elin
authors.initials: SE
authors.lastname: Griffiths
authors.forename: Robert T
authors.initials: RT
authors.lastname: Walton
mesh_terms: D000328:Adult; D016642:Bupropion / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D005731:Ganglionic Stimulants / Q000009:adverse effects* / Q000494:pharmacology*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000009:adverse effects* / Q000494:pharmacology*; D010919:Placebos; D011110:Polymorphism, Genetic; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D012907:Smoking / Q000235:genetics* / Q000523:psychology; D016540:Smoking Cessation; D013375:Substance Withdrawal Syndrome / Q000235:genetics*
chemical_list: D018765:Dopamine Uptake Inhibitors; D005731:Ganglionic Stimulants; D010919:Placebos; D017448:Receptors, Dopamine D2; D016642:Bupropion; D009538:Nicotine