Original article The effects of transcranial direct current stimulation compared to standard bupropion for the treatment of tobacco dependence: A randomized sham-controlled trial Shahram Ghorbani Behnam a , Seyed Abbas Mousavi b , Mohammad Hassan Emamian c, * a Student Research Committee, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran b Center for Health Related Social and Behavioral Sciences Research, Shahroud University of Medical Sciences, Shahroud, Iran c Department of Epidemiology, School of Public Health, Shahroud University of Medical Sciences, Shahroud, Iran A R T I C L E I N F O Article history: Received 10 January 2019 Received in revised form 25 April 2019 Accepted 28 April 2019 Available online xxx Keywords: Dorsolateral prefrontal cortex tDCS Smoking Relapses Iran A B S T R A C T Background: Current treatments for smoking cessation are not effective for most smokers. This study aims to examine the effectiveness of transcranial Direct Current Stimulation (tDCS) on smoking cessation. Methods: In this randomized, sham-controlled trial study, tobacco-dependent (by DSM-5) male participants were recruited from the general public invitation. Participants were randomly allocated to 5 groups; (A), treatment with 300 mg bupropion for 8 weeks; (B), active tDCS (20 sessions for 4 weeks); (C), sham for group B ; (D), active tDCS (20 sessions for 12 weeks), and (E), sham for group D. The electrode montage was anode F3 and cathode F4. Study outcomes include salivary cotinine, Fagerstrom test for nicotine dependence, and smoked cigarette per day, were examined on three time points. Repeated- measures analysis of variances and the generalized estimation equation (GEE) model were employed for data analysis. Results: Among 210 volunteers, 170 participants completed the study. Mean age of participants was 42.9 years, ranging from 21 to 64 years. The 6-month point abstinence rates in groups A, B and D were 20%, 7% and 25.7%, and in C, D sham groups were 3.1% and 3% respectively. Results of the GEE model showed that although group D was not different from group A in abstinence rate, i.e., salivary cotinine >4 (p = 0.266), nicotine dependency by Fagerstrom test was lower in this group compared to group A (p = 0.019). Conclusions: The 12-week tDCS had a clinically good therapeutic effect on smoking cessation and its dependency. It may be a substitute for bupropion treatment. © 2019 Elsevier Masson SAS. All rights reserved. 1. Introduction Tobacco accounts for over 7 million deaths annually [1]. Counseling and medication can increase more than double the success rate for quitting smoking [1]. About 62% of those who attempt to quit smoking on their own with no pharmacotherapy had a relapse in the first two weeks, and only 5% succeed to quit smoking after a year [2]. Smoking cessation is useful at any age for preventing the risk of co-morbidities progression and early mortality [3]. Current smoking cessation methods include counseling [4,5], and nicotine replacement therapy (chewing gum, inhalers, and nicotine patches), with bupropion and Varenicline [6]. Nevertheless, many smokers using these treatments also fail to quit smoking and maintain abstinence for at least six months [6–8]. Over the past decade, transcranial Direct Current Stimulation (tDCS) has been employed as a safe [9], non-invasive brain stimulation method, for addiction treatment and research on this topic is expanding [10]. Research on the effect of tDCS on smokers was mainly focused on the reduction of cue-induced craving [11, 12], ability to resist smoking [13], reduction of negative affect but not cigarette craving in overnight abstinent smokers [14], and motivate smokers to quit smoking [15]. Furthermore, with repeated five sessions of stimulation per week, its cumulative effect decreased craving and even the number of cigarettes smoked [16]. In other studies, anodal stimulation with tDCS has also decreased craving for alcohol and marijuana [17, 18]. Treatment of patients with depression with tDCS revealed maximum therapeu- tic effect after 20 sessions of stimulation (5 sessions per week) in 4 weeks [19]. On the best of our knowledge, no study has so far examined the long-term clinical effects of tDCS on smoking * Corresponding author. E-mail address: emamian@shmu.ac.ir (M.H. Emamian). http://dx.doi.org/10.1016/j.eurpsy.2019.04.010 0924-9338/© 2019 Elsevier Masson SAS. All rights reserved. European Psychiatry 60 (2019) 41–48 Contents lists available at ScienceDirect European Psychiatry journal homepage: http://www.europsy- journal.com