A Review of Smoking Cessation Interventions

Ashish Maseeh, MD, and Gagandeep Kwatra, MD

In This Article

Nonnicotine Drugs

This agent is an atypical antidepressant drug that was investigated for cessation after identification of smoking as a relapsing psychiatric disorder.[78,79] The exact mechanism by which bupropion exerts its therapeutic effect is unclear.[20] It is thought to occur primarily through its dopaminergic actions (inhibition of neural dopamine uptake), although similar adrenergic actions may also have a role.[7,56,80,81] The sustained release formulation is currently the only nonnicotine drug approved by the US Food and Drug Administration for first-line smoking cessation therapy[79] and is suitable for patients who either cannot tolerate NRT or prefer nonnicotine therapy.[4]

Efficacy: Bupropion roughly doubles the smoking cessation rates relative to placebo,[20,25,52] and these rates are significantly higher than with the nicotine patch.[52] Dosage therapy should ideally commence 2 weeks before the cessation date with 150 mg per day for 3 days. This dose should then be increased to 300 mg per day, and therapy should be continued for 7-12 weeks with an extended range up to 6 months.[2]

Advantages: The antidepressant effects of bupropion enable it to remove the gender disparity in smoking cessation rates by preventing the incidence of negative mood swings in women.[79,82] It is well tolerated, has very low abuse potential,[20] and long term cessation-related weight gain is significantly less than with placebo and NRT.[52] It is also a safer alternative to nicotine among pregnant/lactating women and patients with cardiovascular diseases.

Adverse Effects & Disadvantages: The commonly occurring adverse effects include dry mouth, headache, and insomnia.[20,29] These effects can be managed by advising the patient to take frequent sips of water and by avoiding bedtime doses.[4] The possibility exists, however remote, of bupropion inducing seizures.[29] It is therefore contraindicated in patients with history of seizures, anorexia or bulimia, head trauma, or heavy alcohol use.[4]

While all the abovementioned drugs and products are approved for single-drug therapy, combinations may be useful for patients who were unable to quit with monotherapy.[4] Differences exist on whether or not combination therapies are more effective in treating smokers.[34,35,50,83] Most of these products (except the lozenges) can safely be combined with others, although it is unclear if the added benefit is because of higher nicotine levels or for reasons not yet obvious.

After the success of bupropion, several other antidepressant drugs were investigated for smoking cessation. The efficacy of nortriptyline in smoking cessation has been confirmed by several investigators.[83,84] Various factors are thought to play a role, including its antianxiety effects and central adrenergic[85,86] and anticholinergic[87] actions, although a variable combination of these is likely. Clonidine reduces the symptoms of nicotine withdrawal and has been effective for smoking cessation, but the high frequency of adverse effects limits its use.[19]

In another study, sertraline produced a lower total withdrawal symptom score than placebo. It, however, did not potentiate the efficacy of intensive individual counseling in a double-blind, placebo-controlled study.[88] Monoamine oxidase type B inhibitors may also be beneficial in smoking cessation, although drugs with better toxicity profiles need to be evolved, and their coadministration with nicotine products needs to be studied to improve therapeutic efficacy.[89] Studies conducted to evaluate opioid antagonists (naloxone, naltrexone) showed no significant effect of these drugs on long-term abstinence.[90] Smaller clinical trials have suggested that doxepin[91] and fluoxetine[26] are effective, although fluoxetine is used primarily in patients of depression.

Mecamylamine is a nicotine receptor antagonist that acts by inhibiting the rewarding effects of cigarette smoke.[18] Its use, as with clonidine is limited by its side effects, especially those related to ganglionic blockade (orthostatic hypotension, ileus and urinary retention). Lobeline is a partial nicotine antagonist derived from an Indian plant "lobelia inflata," and is used in several commercial products, although scientific evidence of its beneficial effects in smoking cessation is lacking.[92]

A new drug, varenicline has moved recently into phase 3 clinical trials. The manufacturers claim that the drug helps half the smokers to quit in 7 weeks. The authors could not find, however, any impartial scientific literature pertaining to the efficacy, safety, or toxicity profile of this drug.


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