Smoking treatment guided by genetic markers

Abstract

Introduction: Among drug addictions, smoking ranks first as a cause of morbidity and mortality and is a risk factor for six of the eight leading causes of death in the world. Nicotine is the main addictive component of tobacco. In nicotine replacement therapy (NRT), varenicline and bupropion are the approved medications for smoking cessation, but results from smoking cessation clinics suggest that many variables influencing treatment response remain unknow.

Objective: To determine the adherence, tolerability and effectiveness of a smoking cessation program based on nicotine or bupropion, in patients with tobacco dependence, selected according to the genotypes of the enzymes that metabolize the two drugs.

Clinical findings: Twenty-one smokers, 67% men, with mean age of 46.2±11.7 years, were included in this series. Their smoking began at 17.8±6 years and they had been smoking for 28±13 years.

At baseline, they smoked 17±12 cigarettes per day (CPD), had made 3.7±2 quit attempts, the NDSS (Nicotine Dependence Short Scale Screening Scale) score was 22±5 (cut-off point for nicotine dependence: 11 or more points).

Treatment: Patients had free telephone access to the treating physician and, every week, a consultation consisting of counseling and monitoring of the prescribed pharmacological treatment according to CYP2A6 (encoding the enzyme that metabolizes nicotine) and CYP2B6 (encoding the enzyme that metabolizes bupropion) genotypes. Nicotine was used in 14 mg transdermal patches for the first month and then 7 mg for the second month, supplemented with chewing gum for withdrawal management and bupropion in a 300 mg controlled-release form, 1-2 times a day.

Results: After 8 weeks of treatment and 4 weeks of observation, 15 subjects (71.4%) responded partially/totally. CPD consumption dropped from 17±12 at the beginning of the study to 2.2±3.5 at the end of the study, which corresponds to a reduction of 195 cigarettes/day. Seven of eight patients treated with bupropion (87.5%) and seven of thirteen treated with nicotine (54%) had a partial/total response. Only one patient receiving nicotine discontinued the medication due to gastrointestinal intolerance (nausea and vomiting). The relapse rate, assessed one month after drug treatment, was zero. Good genotype-phenotype correlation was found in individuals treated with bupropion, but not in those treated with nicotine.

Clinical relevance: The inclusion of pharmacogenetic markers for the choice of nicotine or bupropion in a smoking cessation program may improve adherence, drug tolerability, and treatment effectiveness.