Primary Projects: Extended Patch
Efficacy of Extended Patch Treatment
Project Leader: Caryn Lerman, Ph.D.
PROJECT DESCRIPTION: Transdermal nicotine (TN) replacement is recommended as a first-line treatment for tobacco dependence. However, there is substantial variability in treatment response, and up to 95% of smokers treated with TN relapse to their former smoking practices. In the absence of empirical data to identify likely responders to TN, practitioners must resort to a less effective one-size-fits-all model of treatment delivery.
Preclinical evidence for nicotine-opioid system interactions suggests that inherited variation in opioid system genes may explain variability in smokers’ responses to nicotine replacement therapy (NRT). Translating existing knowledge of genetic, pharmacologic, and behavioral responses to nicotine, the current study will test whether genetic variation in the mu-opioid receptor gene predicts the efficacy of standard (8 weeks) versus extended treatment (24 weeks) with 21mg transdermal nicotine. Six-hundred consenting smokers of European ancestry homozygous for the OPRM1 Asn40 variant (n=300) or carrying the Asp40 variant (n=300) will be randomized to receive either standard treatment (ST) with TN (21mg x 8 weeks, placebo x 16 weeks) or extended treatment (ET) with TN (21mg x 24 weeks). In addition to TN, participants will receive eight sessions of behavioral counseling. Follow-up surveys will occur at the end of treatment (EOT) and 1 and 6 months after EOT. Data from this trial may lead to the development of new pharmacogenetic treatment models in which treatment decisions about the duration of transdermal nicotine therapy are based on genotype.
LATEST FINDINGS:
The Functional Mu Opiod Receptor (OPRM1) Asn40Asp Variant Predicts Response to Nicotine Replacement Therapy in a Clinical Trial
To determine whether the functional mu-opioid receptor (OPRM1) Asn40Asp variant predicts the comparative efficacy of different forms of NRT, we conducted a clinical trial of transdermal nicotine (TN) versus nicotine nasal spray (NS) in 320 smokers of European ancestry. Smokers carrying the OPRM1 Asp40 variant (n=82) were significantly more likely than those homozygous for the Asn40 variant (n=238) to be abstinent at the end of treatment and reported less mood disturbance and weight gain. The genotype effect on treatment outcome was most pronounced among smokers receiving TN, particularly during the 21mg dose phase. Smokers who carry the OPRM1 Asp40 variant are likely to have a favorable response to TN and may benefit from extended therapy with the 21mg dose.
Lerman C, Wileyto EP, Patterson F, Rukstalis M, Audrain-McGovern J, Restine S, Shields PG, Kaufmann V, Redden D, Benowitz N, Berrettini W. The functional mu opiod receptor (OPRM1) Asn40Asp variant predicts response to nicotine replacement therapy in a clinical trial. Pharmacogenomics. 2004; 4(3): 184-192.
RELATED PUBLICATIONS:
Lerman, C., Tyndale, R., Patterson, F., Wileyto, E. P., Shields, P. G., Pinto, A., & Benowitz, N. (2006). Nicotine metabolite ratio predicts efficacy of transdermal nicotine for smoking cessation. Clin Pharmacol Ther, 79(6), 600-608.
Malaiyandi, V., Lerman, C., Benowitz, N. L., Jepson, C., Patterson, F., & Tyndale, R. F. (2006). Impact of CYP2A6 genotype on pretreatment smoking behaviour and nicotine levels from and usage of nicotine replacement therapy. Mol Psychiatry, 11(4), 400-409.
Colilla, S., Lerman, C., Shields, P. G., Jepson, C., Rukstalis, M., Berlin, J., DeMichele, A., Bunin, G., Strom, B. L., & Rebbeck, T. R. (2005). Association of catechol-O-methyltransferase with smoking cessation in two independent studies of women. Pharmacogenet Genomics, 15(6), 393-398.
Redden, D. T., Shields, P. G., Epstein, L., Wileyto, E. P., Zakharkin, S. O., Allison, D. B., & Lerman, C. (2005). Catechol-O-methyl-transferase functional polymorphism and nicotine dependence: an evaluation of nonreplicated results. Cancer Epidemiol Biomarkers Prev, 14(6), 1384-1389.
Lerman, C., Wileyto, E. P., Rukstalis, M., Audrain-McGovern, J., Restine, S., Patterson, F., Shields, P. G., Kaufmann, V., Redden, D., Benowitz, N., & Berrettini, W. (2004). The functional mu opioid receptor (OPRM1) Asn40Asp variant predicts response to nicotine replacement therapy in a clinical trial. Pharmacogenomics J, 4, 184-192.
Lerman, C., Kaufmann, V., Rukstalis, M., Patterson, F., Perkins, K., Audrain-McGovern, J., & Benowitz, N. (2004). Individualizing nicotine replacement therapy for the treatment of tobacco dependence: a randomized trial. Ann Intern Med, 140(6), 426-433.
ADDITIONAL CITATIONS:
Munafo MR, Shields AE, Berrettini WH, Patterson F, Lerman C. Pharmacogenetics and nicotine addiction. Pharmacogenomics, in press.