An open-label pilot trial of N-acetylcysteine and varenicline in adult cigarette smokers

Abstract

Background: Varenicline (VAR) has demonstrated superior efficacy over other smoking cessation pharmacotherapies, though 50–60% of those treated do maintain abstinence. Some preclinical findings suggest that new nicotine dependence pharmacotherapies should target the glutamatergic system, given its demonstrated role in addiction. Attention has been given to N-acetylcysteine (NAC), which appears to restore normal glutamate signaling in animal models. It is possible that NAC and VAR may work in concert to promote abstinence at higher rates than with either medication alone. Objective: To demonstrate the feasibility and safety of co-administering NAC and VAR in nicotine-dependent participants. Methods: Participants (n = 19) were daily cigarette smokers, and did not need to be seeking treatment. They received 4 weeks of open-label treatment with NAC (1200 mg twice daily) and VAR (1 mg twice daily, following titration) and were assessed weekly for adverse events (AEs), smoking, craving and withdrawal. Results: Sixteen participants reported a total of 40 AEs, and most were mild (88%). The most commonly reported AE was nausea (15%). Medication adherence, assessed via self-reports and pill counts, was excellent (98%). Exploratory analyses showed reductions in cigarettes per day, though point prevalence abstinence at the end of the study was low. Conclusions: These preliminary data provide the first demonstration of safety and feasibility of the co-administration of NAC and VAR in cigarette smokers. AEs were consistent with those typically reported for VAR and NAC. These data support future efficacy research on NAC and VAR for smoking cessation.

• N-acetylcysteine
• pharmacotherapy
• smoking cessation
• safety
• tolerability
• varenicline

Acknowledgements

The authors wish to acknowledge the funding sources for this study. Funding was provided by NIDA grants P50DA015369 (PI, Peter W. Kalivas) and U01DA031779 (PI, Kevin M. Gray). Additional support was also provided by the South Carolina Clinical and Translational Institute at the Medical University of South Carolina (UL1TR000062). The funding source had no role other than financial support. The authors would like to thank the medical and research staff of the Clinical Neuroscience Division at the Medical University of South Carolina. Specifically, we would like to thank Jessica Hinton, Danielle Paquette, Priscilla Muldrow, Casy Johnson, Christine Horne, Lori Ann Ueberroth, and Elisabeth Kryway for their assistance with data collection, management, study coordination, and participant safety.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper. All authors contributed to the design and execution of the study, analyses of data, and manuscript preparation. All authors have read and approved the manuscript.