N-acetylcysteine as an adjunctive treatment for smoking cessation: a randomized clinical trial

Regina C B R Machado, Heber O Vargas, Marcela M Baracat, Mariana R Urbano, Waldiceu A Verri Jr, Mauro Porcu, Sandra O V Nunes, Regina C B R Machado, Heber O Vargas, Marcela M Baracat, Mariana R Urbano, Waldiceu A Verri Jr, Mauro Porcu, Sandra O V Nunes

Abstract

Objective: This randomized controlled trial examined the efficacy and safety of N-acetylcysteine as an adjunctive treatment for smoking cessation.

Methods: Heavy smokers were recruited from smoking cessation treatment for this 12- week randomized controlled trial. Eligible tobacco use disorder outpatients (n=34) were randomized to N-acetylcysteine or placebo plus first-line treatment. Abstinence was verified by exhaled carbon monoxide (COexh). The assessment scales included the Fagerström Test for Nicotine Dependence, the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, the Minnesota Nicotine Withdrawal Scale, and the Medication Adherence Rating Scale. We also assessed anthropometrics, blood pressure, lipid profile, and soluble tumor necrosis factor receptor (sTNF-R) levels 1 and 2.

Results: First-line treatment for smoking cessation plus adjunctive N-acetylcysteine or placebo significantly reduced COexh (p < 0.01). In the N-acetylcysteine group, no significant changes were found in nicotine withdrawal symptoms, depressive and anxiety symptoms, anthropometric measures, blood pressure, or glucose compared to placebo. However, there was a significant reduction in sTNF-R2 levels between baseline and week 12 in the N-acetylcysteine group.

Conclusions: These findings highlight the need to associate N-acetylcysteine with first-line treatment for smoking cessation, since combined treatment may affect inflammation and metabolism components.

Clinical trial registration: NCT02420418.

Conflict of interest statement

The authors report no conflicts of interest.

References

    1. GBD 2015 Tobacco Collaborators. Smoking prevalence and attributable disease burden in 195 countries and territories, 1990-2015: a systematic analysis from the Global Burden of Disease Study 2015. Lancet. 2017;389:1885–906.
    1. Centers for Disease Control and Prevention (CDC) Quitting smoking among adults: United States, 2001-2011. MMWR Morb Mortal Wkly Rep. 2011;60:1513–9.
    1. Danovitch I. The clinical assessment and treatment of nicotine dependence. Focus. 2011;9:15–24.
    1. Gonzales D, Rennard SI, Nides M, Oncken C, Azoulay S, Billing CB, et al. Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. JAMA. 2006;296:47–55.
    1. McClure EA, Gipson CD, Malcolm RJ, Kalivas PW, Gray KM. Potential role of N-acetylcysteine in the management of substance use disorders. CNS Drugs. 2014;28:95–106.
    1. Berk M, Malhi GS, Gray LJ, Dean OM. The promiseof N-acetylcysteine in neuropsychiatry. Trends Pharmacol Sci. 2013;34:167–77.
    1. Dean O, Giorlando F, Berk M. N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action. J Psychiatry Neurosci. 2011;36:78–86.
    1. Kalivas PW, Volkow ND. The neural basis of addiction: a pathology of motivation and choice. Am J Psychiatry. 2005;162:1403–13.
    1. Knackstedt LA, LaRowe S, Mardikian P, Malcolm R, Upadhyaya H, Hedden S, et al. The role of cystine-glutamate exchange in nicotine dependence in rats and humans. Biol Psychiatry. 2009;65:841–5.
    1. Schmaal L, Berk L, Hulstijn KP, Cousijn J, Wiers RW, van den Brink W. Efficacy of N-acetylcysteine in the treatment of nicotine dependence: a double-blind placebo-controlled pilot study. Eur Addict Res. 2011;17:211–6.
    1. Prado E, Maes M, Piccoli LG, Baracat m, Barbosa ds, Franco o, et al. N-acetylcysteine for therapy-resistant tobacco use disorder: a pilot study. Redox Rep. 2015;20:215–22.
    1. Mokhtari V, Afsharian P, Shahhoseini M, Kalantar SM, Moini A. A review on various uses of N-acetyl cysteine. Cell J. 2017;19:11–7.
    1. Ma Y, Gao M, Liu D. N-acetylcysteine protects mice from high fat diet-induced metabolic disorders. Pharm Res. 2016;33:2033–42.
    1. Brasil, Ministério da Saúde, Secretaria de Atenção à Saúde. Portaria SAS/MS 442/04 de 13 de agosto de 2004. Diário Oficial da União, 17 de agosto de. 2004. .
    1. Brasil, Ministério da Saúde. Portaria GM/MS 571 de 05 de abril de 2013. Diário Oficial da União, 08 de abril de. 2013. pp. 56–7. .
    1. Brasil, Ministério da Saúde, Instituto Nacional de Câncer, Coordenação de Prevenção e Vigilância. Abordagem e tratamento do fumante: consenso. Rio de Janeiro: INCA; 2001. .
    1. Nunes SOV, Vargas HO, Castro MR, Machado RCB, Carmo DR. Abordagem intensiva. In: Nunes SOV, Castro MRP, editors. Abordagem, prevenção e tratamento do tabagismo. Londrina: Eduel; 2011. pp. 97–216.
    1. Nunes SOV, de Castro MRP, Vargas HO, Vargas MM, de Batista Fonseca IC. Clinical characteristics and smoking cessation: an analysis of sex and depressive disorders differences. Addict Disord Their Treat. 2013;12:158–65.
    1. Arancini L, Bortolasci CC, Dodd S, Dean OM, Berk M. N-acetylcysteine for cessation of tobacco smoking: rationale and study protocol for a randomised controlled trial. Trials. 2019;20:555.
    1. Heatherton TF, Kozlowski LT, Frecker RC, Fagerström KO. The Fagerström test for nicotine dependence: a revision of the Fagerström tolerance questionnaire. Br J Addict. 1991;86:1119–27.
    1. do Carmo JT, Pueyo AA. A adaptação ao português do Fagerström test for nicotine dependence (FTND) para avaliar a dependência e tolerância à nicotina em fumantes brasileiros. Rev Bras Med. 2002;59:73–80.
    1. Fagerström KO, Kunze M, Schoberberger R, Breslau N, Hughes JR, Hurt RD, et al. Nicotine dependence versus smoking prevalence:comparisons among countries and categories of smokers. Tob Control. 1996;5:52–6.
    1. Gallus S, La Vecchia C. A population-based estimate of tobacco dependence. Eur J Public Health. 2004;14:93–4.
    1. Diaz FJ, Jane M, Salto E, Pardell H, Salleras L, Pinet C, et al. A brief measure of high nicotine dependence for busy clinicians and large epidemiological surveys. Aust N Z J Psychiatry. 2005;39:161–8.
    1. Kozlowski LT, Porter CQ, Orleans CT, Pope MA, Heatherton T. Predicting smoking cessation with self-reported measures of nicotine dependence: FTQ, FTND, and HSI. Drug Alcohol Depend. 1994;34:211–6.
    1. Del Ben CM, Vilela JAA, Crippa JAS, Hallak JEC, Labate CM, Zuardi AW. Confiabilidade da “Entrevista Clínica Estruturada para o DSM-IV” – versão clínica traduzida para o português. Rev Bras Psiquiatr. 2001;23:156–9.
    1. Organização Mundial da Saúde (OMS) Classificação de transtornos mentais e de comportamento da CID-10: descrições clínicas e diretrizes diagnósticas. Porto Alegre: Artmed; 1993.
    1. Moreno RA, Moreno DH. Escalas de depressão de Montgomery & Asberg (MADRS) e de Hamilton (HAM-D) Rev Psiquiatr Clin (São Paulo) 1998;25:262–72.
    1. Hamilton M. The assessment of anxiety states by rating. Br J Med Psychol. 1959;32:50–5.
    1. Hughes JR, Hatsukami D. Signs and symptoms of tobacco withdrawal. Arch Gen Psychiatry. 1986;43:289–94.
    1. Thompson K, Kulkarni J, Sergejew AA. Reliability and validity of a new medication adherence rating scale (MARS) for the psychoses. Schizophr Res. 2000;42:241–7.
    1. Vanelli I, Chendo I, Gois C, Santos J, Levy P. [Medication adherence rating scale] Acta Med Port. 2011;24:17–20.
    1. Millán J, Pintó X, Muñoz A, Zúñiga M, Rubiés-Prat J, Pallardo LF, et al. Lipoprotein ratios: physiological significance and clinical usefulness in cardiovascular prevention. Vasc Health Risk Manag. 2009;5:757–65.
    1. R Development Core Team. R: a language and environment for statistical computing [Internet] 2017. [[cited 2020 May 29]].
    1. Fiore MC, Jaén CR, Beker TB, Bailey WC, Benowitz NL, Curry SJ, et al. Clinical practice guideline: Treating tobacco use and dependence: 2008 update [Internet] 2008 May. [[cited 207 Sep 28]]. .
    1. Asevedo E, Mendes AC, Berk M, Brietzke E. Systematic review of N-acetylcysteine in the treatment of addictions. Braz J Psychiatry. 2014;36:168–75.
    1. Liechti ME, Lhuillier L, Kaupmann K, Markou A. Metabotropic glutamate 2/3 receptors in the ventral tegmental area and the nucleus accumbens shell are involved in behaviors relating to nicotine dependence. J Neurosci. 2007;27:9077–85.
    1. Nunes SO, Vargas HO, Brum J, Prado E, Vargas MM, de Castro MR, et al. A Comparison of inflammatory markers in depressed and nondepressed smokers. Nicotine Tob Res. 2012;14:540–6.
    1. Aldaham S, Foote JA, Chow HH, Hakim IA. Smoking Status Effect on Inflammatory Markers in a Randomized Trial of Current and Former Heavy Smokers. Int J Inflam. 2015;2015:439396.
    1. Filozof C, Fernandez Pinilla MC, Fernández-Cruz A. Smoking cessation and weight gain. Obes Rev. 2004;5:95–103.
    1. Eisenberg D, Quinn BC. Estimating the effect of smoking cessation on weight gain: an instrumental variable approach. Health Serv Res. 2006;41:2255–66.
    1. Johnson HM, Gossett LK, Piper ME, Aeschlimann SE, Korcarz CE, Baker TB, et al. Effects of smoking and smoking cessation on endothelial function: 1-year outcomes from a randomized clinical trial. J Am Coll Cardiol. 2010;55:1988–95.
    1. Harris KK, Zopey M, Friedman TC. Metabolic effects of smoking cessation. Nat Rev Endocrinol. 2016;12:299–308.

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