Psychotropic agents (commonly used to treat depression) are sometimes used to treat nicotine addiction because they regulate receptors in the brain that are affected by nicotine.

Bupropion (Zyban) is only available by prescription. Unlike nicotine replacement therapies, which typically begin on the smoker's quitting day, smokers begin taking bupropion 1–2 weeks before they quit smoking. The initial dose is 150 mg in the morning for 3 days, and then 150 mg twice a day, continuing for 7–12 weeks.

Bupropion should not be used by anyone with a history of a seizure or eating disorder. Patients who are using another form of bupropion or who have used a monoamine oxidase inhibitor (MAOI) in the past 14 days also should not use bupropion. People taking bupropion should limit alcohol consumption.

Side effects may include hypertension, tremor, insomnia, and dry mouth. Zyban is not recommended for women who are pregnant or nursing.

Varenicline (Chantix) is a non-nicotine medication that is available by prescription for smoking cessation. This drug attaches to nicotine receptors in the brain, helps block nicotine from reaching these receptors, and may reduce the release of dopamine triggered by nicotine. Varenicline also is taken for 1 week before the smoker's quitting day to allow the medicine to build up in the body.

Side effects may include nausea and vomiting, constipation, and difficulty sleeping. In some cases, a serious reaction can occur. Signs of a severe reaction include swelling of the face, mouth, and throat and redness, swelling, and peeling of the skin.

In 2009, the U.S. Food and Drug Administration (FDA) issued a black box warning for the smoking cessation drugs bupropion and varenicline. According to the FDA, these medications carry an increased risk for mental health side effects, such as depression, behavioral changes (e.g., hostility, irritability), and suicidal thoughts. Patients who use these drugs to stop smoking should be closely monitored while taking them and after the medication is discontinued.

In July 2011, the FDA updated labeling for Chantix to include new information about the effectiveness of the drug for people with stable heart disease and mild or moderate COPD who are trying to quit smoking. Studies have shown that Chantix is effective in these patients—in some cases, almost doubling the chance of quitting for at least one year. These same studies shown that a slight increased risk for adverse cardiovascular events is possible in people with heart disease who use Chantix.

In March 2015, the FDA approved updates to the Chantix label to include warnings that the drug can change the way a person reacts to alcohol, and that rare accounts of seizures in people taking the drug have been reported. An additional update approval included a warning that several studies have shown an increased risk for neuropsychiatric side effects on mood, behavior, and thinking in people who take Chantix.

Clonidine, a commonly used antihypertensive, is available only by prescription in oral and transdermal form. It has not been approved by the FDA for the treatment of smoking cessation and is used only as a second-line therapy if first-line therapies have been unsuccessful.

Clonidine doses vary from 0.15–0.75 mg per day (oral form) to 0.10–0.20 mg per day (transdermal form) and the duration of treatment varies from 3–10 weeks. Treatment begins up to 3 days before quitting or on the quit date. The patient puts a new patch (transdermal form) on relatively hairless skin between the neck and waist each week.

While clonidine is effective, its side effects limit its usefulness. The most common side effects include dry mouth, drowsiness, dizziness, sedation, and constipation. Because clonidine lowers blood pressure in most patients, any reduction in dosage must be done gradually over 2-4 days to reduce the risk for rebound hypertension, marked by a rapid increase in blood pressure, agitation, confusion, and tremor.

Nortriptyline (Nortriptyline HCl) is only available by prescription. This antidepressant has not been approved by the FDA for smoking cessation and is recommended only if first-line therapies have been unsuccessful.

Patients begin taking nortriptyline 10–28 days before quitting. It is taken orally in doses of 25 mg per day, increasing to 75–100 mg per day for 12 weeks. Side effects include sedation, dry mouth, blurred vision, urinary retention, lightheadedness, shaky hands, and constipation. Overdose with nortriptyline can have cardiotoxic effects and it should be used with extreme caution.

Updated by Remedy Health Media

Publication Review By: Stanley J. Swierzewski, III, M.D.

Published: 15 Jul 2006

Last Modified: 10 Mar 2015