37 For patients with a history of depression, the bupropion dose is equivalent, allowing for the pharmacological treatment of both disorders simultaneously.6 Side effects of bupropion primarily consist of gastrointestinal symptoms, rash, headache, insomnia, and dry

mouth.38 As with other antidepressants, bupropion lowers seizure threshold, so it should not be used in patients with a history of seizure disorders. 6 Second-line pharmacotherapies for smoking cessation include Inhibitors,research,lifescience,medical nortriptyline, clonidine, selegiline and, most recently, varenicline. Nortriptyline, like bupropion, is an antidepressant that shows promising effects for smoking cessation.39,40 It may also be useful in the treatment of depressed cigarette smokers; however, its efficacy does not appear to depend on comorbidity Inhibitors,research,lifescience,medical with a depressive disorder. 6 Vismodegib Though shown to be efficacious, nortriptyline has significant side effects which limit its safety (eg, risk of toxicity in overdose amounts).6 Clonidine, an antihypertensive agent, is an α-22-adrenergic receptor agonist that decreases central sympathetic activity. It may be an effective treatment option for those who have failed other smoking cessation methods. Side effects from its clinical use include sedation, dizziness, dry mouth, constipation, and orthostatic hypotension.41-43

Inhibitors,research,lifescience,medical Other agents (eg selegiline and mecamylamine) have also been studied, but their efficacy for smoking cessation has not yet been established.

For example selegiline, a monoamine oxidase-B (MAO-B) inhibitor for the treatment of Parkinson’s disease may also be useful in reducing nicotine craving by decreasing dopamine metabolism.44-45 Partial agonist Varenicline, an α4β2 nicotinic acetylcholine receptor Inhibitors,research,lifescience,medical partial agonist, is an efficacious treatment for smoking cessation. Clinical Inhibitors,research,lifescience,medical trials indicate that this partial agonist can reduce craving and withdrawal symptoms following cessation or reduction of nicotine consumption. In addition its partial antagonism can also reduce smoking satisfaction through the occupation of the receptors and blocking the full agonist nicotine from binding.46 Varenicline, administered 1 mg twice daily, has demonstrated superiority to placebo and bupropion.46,47 It is generally safe and Farnesyltransferase well tolerated. Nausea and insomnia are commonly reported adverse reactions to varenicline.46,47 Nicotine vaccine Currently, three nicotine vaccines have completed phase I-II clinical trials; NicVAX, CYT002-NicOb, and TA-NIC. In a phase II clinical trial, 68 smokers were randomized to receive one of 3 doses of a nicotine conjugate vaccine, NicVax (50, 100, or 200 µg) or placebo. The vaccine was shown to be safe and well tolerated. In addition, vaccine immunogenicity was dose-related (P<0.001) with the highest rate of 30-day abstinence occurring with 200 µg (P<0.02).