Human Laboratory Study of Varenicline and Bupropion for Nicotine Dependence

Summary

The objective of this proposal is to elucidate effects of bupropion SR + varenicline on smoking-cessation related processes in early abstinence using a human laboratory model. A within-subjects design will be used to assess the additive effects of bupropion and varenicline in 48 treatment seeking smokers \[bupropion SR (300 mg/day)+placebo, varenicline (2 mg/day+placebo, and bupropion SR (300 mg/day)+varenicline (2 mg/day)\]. Outcomes include withdrawal and craving, cognition, stress tolerance, anxiety, the reinforcing effects of smoking, and smoking topography. Hypotheses: We hypothesize that greatest treatment effects will be observed in the bupropion SR+varenicline group followed by varenicline+placebo and bupropion SR+placebo groups.

Timeline

Start

2008-11

Primary completion

2010-09

Completion

2010-09

Publications

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• Background Croghan GA, Sloan JA, Croghan IT, Novotny P, Hurt RD, DeKrey WL, Mailliard JA, Ebbert LP, Swan DK, Walsh DJ, Wiesenfeld M, Levitt R, Stella P, Johnson PA, Tschetter LK, Loprinzi C. Comparison of nicotine patch alone versus nicotine nasal spray alone versus a combination for treating smokers: a minimal intervention, randomized multicenter trial in a nonspecialized setting. Nicotine Tob Res. 2003 Apr;5(2):181-7. doi: 10.1080/1462220031000073252.
• Background Croghan IT, Hurt RD, Dakhil SR, Croghan GA, Sloan JA, Novotny PJ, Rowland KM, Bernath A, Loots ML, Le-Lindqwister NA, Tschetter LK, Garneau SC, Flynn KA, Ebbert LP, Wender DB, Loprinzi CL. Randomized comparison of a nicotine inhaler and bupropion for smoking cessation and relapse prevention. Mayo Clin Proc. 2007 Feb;82(2):186-95. doi: 10.4065/82.2.186.
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• Background Kornitzer M, Boutsen M, Dramaix M, Thijs J, Gustavsson G. Combined use of nicotine patch and gum in smoking cessation: a placebo-controlled clinical trial. Prev Med. 1995 Jan;24(1):41-7. doi: 10.1006/pmed.1995.1006.
• Background Krishnan-Sarin S, Meandzija B, O'Malley S. Naltrexone and nicotine patch smoking cessation: a preliminary study. Nicotine Tob Res. 2003 Dec;5(6):851-7. doi: 10.1080/14622200310001614601.
• Background O'Malley SS, Cooney JL, Krishnan-Sarin S, Dubin JA, McKee SA, Cooney NL, Blakeslee A, Meandzija B, Romano-Dahlgard D, Wu R, Makuch R, Jatlow P. A controlled trial of naltrexone augmentation of nicotine replacement therapy for smoking cessation. Arch Intern Med. 2006 Mar 27;166(6):667-74. doi: 10.1001/archinte.166.6.667.
• Background Piper ME, Federman EB, McCarthy DE, Bolt DM, Smith SS, Fiore MC, Baker TB. Efficacy of bupropion alone and in combination with nicotine gum. Nicotine Tob Res. 2007 Sep;9(9):947-54. doi: 10.1080/14622200701540820.
• Background Rose JE, Behm FM, Westman EC. Nicotine-mecamylamine treatment for smoking cessation: the role of pre-cessation therapy. Exp Clin Psychopharmacol. 1998 Aug;6(3):331-43. doi: 10.1037//1064-1297.6.3.331.
• Background Williams J, Ziedonis DM. Naltrexone-bupropion combination therapy for protracted abstinence dysphoria. Am J Addict. 2003 May-Jun;12(3):270-2. No abstract available.
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• Background Ascher JA, Cole JO, Colin JN, Feighner JP, Ferris RM, Fibiger HC, Golden RN, Martin P, Potter WZ, Richelson E, et al. Bupropion: a review of its mechanism of antidepressant activity. J Clin Psychiatry. 1995 Sep;56(9):395-401.
• Background Coe JW, Brooks PR, Vetelino MG, Wirtz MC, Arnold EP, Huang J, Sands SB, Davis TI, Lebel LA, Fox CB, Shrikhande A, Heym JH, Schaeffer E, Rollema H, Lu Y, Mansbach RS, Chambers LK, Rovetti CC, Schulz DW, Tingley FD 3rd, O'Neill BT. Varenicline: an alpha4beta2 nicotinic receptor partial agonist for smoking cessation. J Med Chem. 2005 May 19;48(10):3474-7. doi: 10.1021/jm050069n.
• Background Mooney ME, Sofuoglu M. Bupropion for the treatment of nicotine withdrawal and craving. Expert Rev Neurother. 2006 Jul;6(7):965-81. doi: 10.1586/14737175.6.7.965.
• Background Warner C, Shoaib M. How does bupropion work as a smoking cessation aid? Addict Biol. 2005 Sep;10(3):219-31. doi: 10.1080/13556210500222670.
• Background Johnston AJ, Ascher J, Leadbetter R, Schmith VD, Patel DK, Durcan M, Bentley B. Pharmacokinetic optimisation of sustained-release bupropion for smoking cessation. Drugs. 2002;62 Suppl 2:11-24. doi: 10.2165/00003495-200262002-00002.
• Background Bondarev ML, Bondareva TS, Young R, Glennon RA. Behavioral and biochemical investigations of bupropion metabolites. Eur J Pharmacol. 2003 Aug 1;474(1):85-93. doi: 10.1016/s0014-2999(03)02010-7.
• Background Hughes JR, Keely JP, Niaura RS, Ossip-Klein DJ, Richmond RL, Swan GE. Measures of abstinence in clinical trials: issues and recommendations. Nicotine Tob Res. 2003 Feb;5(1):13-25.
• Background SRNT Subcommittee on Biochemical Verification. Biochemical verification of tobacco use and cessation. Nicotine Tob Res. 2002 May;4(2):149-59. doi: 10.1080/14622200210123581. No abstract available.
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• Background Shiffman S, Johnston JA, Khayrallah M, Elash CA, Gwaltney CJ, Paty JA, Gnys M, Evoniuk G, DeVeaugh-Geiss J. The effect of bupropion on nicotine craving and withdrawal. Psychopharmacology (Berl). 2000 Jan;148(1):33-40. doi: 10.1007/s002130050022.
• Background Kotlyar M, Brauer LH, al'absi M, Adson DE, Robiner W, Thuras P, Harris J, Finocchi ME, Bronars CA, Candell S, Hatsukami DK. Effect of bupropion on physiological measures of stress in smokers during nicotine withdrawal. Pharmacol Biochem Behav. 2006 Mar;83(3):370-9. doi: 10.1016/j.pbb.2006.02.017. Epub 2006 Mar 6.
• Background Gonzales D, Rennard SI, Nides M, Oncken C, Azoulay S, Billing CB, Watsky EJ, Gong J, Williams KE, Reeves KR; Varenicline Phase 3 Study Group. Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. JAMA. 2006 Jul 5;296(1):47-55. doi: 10.1001/jama.296.1.47.
• Background Jorenby DE, Hays JT, Rigotti NA, Azoulay S, Watsky EJ, Williams KE, Billing CB, Gong J, Reeves KR; Varenicline Phase 3 Study Group. Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. JAMA. 2006 Jul 5;296(1):56-63. doi: 10.1001/jama.296.1.56.
• Background Nides M, Oncken C, Gonzales D, Rennard S, Watsky EJ, Anziano R, Reeves KR. Smoking cessation with varenicline, a selective alpha4beta2 nicotinic receptor partial agonist: results from a 7-week, randomized, placebo- and bupropion-controlled trial with 1-year follow-up. Arch Intern Med. 2006 Aug 14-28;166(15):1561-8. doi: 10.1001/archinte.166.15.1561.

Drugs

Indications