The study will be conducted at the Center of Smoking Cessation, at State University (UEL), in Brazil. A sample of 32 outpatients will be selected, that are refractory to first-line smoking cessation treatment. All patients included in this study under the condition of understanding and signing the informed consent after approval of the research by Ethics Research Committee of UEL. Prior to randomization into the clinical trial, all participants will be assessed with a questionnaire to provide information about demographic, smoking history, nicotine dependence, depressive disorder, anthropometric measurements such as , height, weight, body mass index (BMI), waist circumference (WC), as well as heart rate (HR) and blood pressure (BP).The diagnostic criteria for research for depressive disorder and tobacco use disorder will be assed by trained psychiatrists according to the Structured Clinical Interview. The primary outcome measurement will be the significant reduction on the number of cigarettes/day. Secondary outcome measurements will be: reduction on the exhaled Carbon Monoxide, reduction of Hamilton Depression Rating Scale scores, improvement on Sheehan Quality of Life scale measurements.

The Fagerstrom Test for nicotine dependence (FTND) will be used to assess the severity of tobacco by dependence FTND. The FTND has a scale of six items and the score 0-10. The cutoff point for FTND nicotine dependence will be \> 5. The assessment of severity of depression among study participants will be conducted by using Hamilton Depression Rating Scale- 17 items (HDRS). HDRS was translated and adapted for the Brazilian population. Minnesota Nicotine Withdrawal Scale (MNWS) MNWS is a 5-point scale (none, slight, mild, moderate, severe) to measure withdrawal symptoms.The scale assesses the damage that the patient is having due to illness. It is a self - administered scale consisting of 3 items. A score of 0-10 corresponds to the patient's opinion. Assesses the disability damage in three areas: 1) occupational, 2) social life, leisure, 3) family life, activities, and household activities. Can be scored 0-10, 0-3 mild injury, 4-6 moderate damage and 7-10 injury grave.The number of pack-years was calculated according to the definition: the number of cigarettes smoked per day multiplied by number of years smoked and divided by 20 (1 pack has 20 cigarettes).This clinical trial was designed to investigate the efficacy of NAC as a treatment for tobacco use disorder. Data were collected by face-to-face interview at baseline and weeks 4, 8 and 12. Smoking status was also evaluated using exhaled carbon monoxide (COEXH). COEXH was measured using a Micro CO Meter with an electrochemical sensor (Micro CO - Micro Medical Ltd, Rochester, Kent, UK). All participants were instructed to breathe deeply and to hold their breath for 20 seconds and then to exhale slowly and completely through a mouthpiece. Smoking reduction was validated by breath carbon monoxide concentration, and the cut-off point for COEXH levels will be categorized as ≤ 6ppm for smoking cessation (Middleton et al., 2000). Both groups will receive monthly meetings of Group Behavioral Therapy during the course of the study.

Participants (n=32) were randomized into two groups 16 patients in each group, in a double-blind manner to receive NAC or placebo. The dose of NAC was 3000mg/day administered in 500 mg capsules in two daily doses, 3 capsules in the morning and 3 in the evening. The chosen dosage was based on previous studies in which similar dosages had shown to be effective and well tolerated.

Individuals were randomized to NAC or placebo, each group have individuals with equal gender, age, scores of FTND and depressive disorders.

Statistical analysis will be performed with repeated measurements design analyses of variance, and post hoc t test.