Present address: Kiadis Pharma, Amsterdam, the Netherlands.
Genetic variants in the serotonin transporter influence the efficacy of bupropion and nortriptyline in smoking cessation
Article first published online: 21 SEP 2011
© 2011 The Authors, Addiction © 2011 Society for the Study of Addiction
Volume 107, Issue 1, pages 178–187, January 2012
How to Cite
Quaak, M., van Schayck, C. P., Postma, D. S., Wagena, E. J. and van Schooten, F. J. (2012), Genetic variants in the serotonin transporter influence the efficacy of bupropion and nortriptyline in smoking cessation. Addiction, 107: 178–187. doi: 10.1111/j.1360-0443.2011.03534.x
- Issue published online: 12 DEC 2011
- Article first published online: 21 SEP 2011
- Accepted manuscript online: 9 JUN 2011 10:01AM EST
- Submitted 14 February 2011; initial review completed 30 March 2011; final version accepted 31 May 2011
- serotonin plasma membrane transport protein (5-HTT) gene (SLC6A4);
- smoking cessation;
- STin2 VNTR
Aims We investigated whether variants in the serotonin transporter gene (SLC6A4) influence smoking cessation rates using antidepressant therapy (i.e. bupropion and nortriptyline).
Design Pharmacogenetic (secondary) analysis of a randomized, placebo-controlled efficacy trial of bupropion and nortriptyline for smoking cessation.
Setting Single-centre study, Maastricht University, the Netherlands.
Participants A total of 214 of 255 (84%) current daily smokers participating in a randomized controlled efficacy trial.
Measurements Subjects were genotyped for three functional variants in SLC6A4 (5-HTTLPR, STin2, rs25531). Primary outcome measures were prolonged abstinence from weeks 4–12, 4–26 and 4–52. Secondary outcome measures included 7-day point prevalence abstinence at weeks 4, 12, 26 and 52.
Findings Carriers of the 5-HTTLPR high-activity L-variant had higher prolonged cessation rates with bupropion than placebo [odds ratio (OR) = 1.44, 95% confidence interval (CI) = 1.01–2.05, P = 0.04]. Combining the three variants resulted in increased prolonged cessation rates for both bupropion and nortriptyline among carriers of four to five high-activity variants (bupropion: OR = 2.00, 95% CI = 1.21–3.29, P = 0.01; nortriptyline: OR = 1.91, 95% CI = 1.02–3.56, P = 0.04). Similar results were found for point prevalence abstinence.
Conclusions Bupropion and nortriptyline seem to be more effective in smoking cessation among SLC6A4 high-activity variant carriers, probably by blocking the increased serotonin transporter activity, thereby increasing serotonin levels. Prospective studies have to assess if this can improve cessation rates when treatment is targeted at individuals based on their genotypes.