Int. J. Environ. Res. Public Health 2009, 6 213 stages before they finally take the decision to make a cessation attempt and at last succeed with their intentions and stop smoking. Smoking cessation advice or other interventions appear to have their effect by triggering a cessation attempt. Each year about 2% of smokers succeed in quitting on their own initiative [39]. Smoking cessation is challenging and behavioral interventions alone have had only modest success; as a result drug therapy has been increasingly relied upon to assist in smoking cessation. The most common of these pharmacologic interventions has been nicotine replacement therapy (NRT) [40]. More recently, attention has focused on the use of anti-depressant therapy [4, 41]. Pharmacologic smoking cessation aids are recommended for all smokers trying to quit, unless contraindicated [42]; smokers should also be provided with counseling when attempting to quit [39]. Family physicians can play an important role in the smoking cessation process, given that 70% of smokers consult family physicians annually [43]. As mentioned, most smokers who attempt to quit do not utilize cessation aids, and as a result, they are usually unsuccessful with two-thirds relapsing within 48 hours [44]. For this reason, all smokers— including those who may be at risk for COPD as well as those who already have the disease — should be offered the most intensive smoking cessation intervention possible. Even a brief period of counseling at the doctor’s office to urge a smoker to quit, results in smoking cessation rates of 5 to 10% [45-47]. At the very least, this should be done for every smoker at every health care provider visit [48-51]. The rate of successful smoking cessation at one year is of 3-5% when the patient simply tries to stop, from 7-16% if the smoker undergoes behavioral intervention and up to 24% when receiving pharmacological treatment plus behavioral support. Recently, several meta-analyses have shown that all current pharmacotherapies for smoking cessation are twice as likely more efficacious than placebo [52-54]. Table 1. Efficacy of pharmacologic treatment for smoking cessation *. Treatment Experimental group Control Group OR (CI95%) Nicotine gum 19.5% 11.5% 1.66 (1.52, 1.81) Nicotine patch 14.6% 8.6% 1.81 (1.63, 2.02) Nicotine inhaler 17.15 9.1% 2.14 (1.44, 3.18) Bupropion 20.0% 10.2% 1.94 (1.72, 2.19) Varenicline 23.0% 10.3% 2.66 (1.72.4.11) *Modified from Schmelzle, J., et al. [43] Pharmacologic agents are classified as first-line pharmacotherapy, which includes nicotine replacement therapy, bupropion and varenicline and second-line agents such as nortriptyline, a tricyclic antidepressant agent, and clonidine, an antihypertensive drug [54]. 5. Nicotine Replacement Therapy Most regular smokers are addicted to nicotine. When a subject smokes a cigarette, nicotine will get into the bloodstream and almost immediately stimulate the brain. In regular smokers, when the blood level of nicotine decreases, withdrawal symptoms such as restlessness, increased appetite, inability to concentrate, irritability, dizziness, and nicotine craving will develop. These symptoms begin within a