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Prescription drugs are also available to help smokers quit. Some can be used along with nicotine replacement therapy (NRT), and some must be started before your planned Quit Day. Talk to your doctor if you want to use medicine to help you quit smoking. You will need a prescription for any of these drugs.

Bupropion (Zyban)

Bupropion (brand names are Zyban®, Wellbutrin®, or Aplenzin®) is a prescription anti-depressant in an extended-release form that reduces symptoms of nicotine withdrawal. It does not contain nicotine. This drug acts on chemicals in the brain that are related to nicotine craving. Bupropion works best if it’s started 1 or 2 weeks before you quit smoking. The usual dosage is one or two 150 mg tablets per day.

If you are able to quit smoking after 7 to 12 weeks of bupropion your doctor may have you keep taking it for some time afterward to help keep you from going back to smoking. Keep up with your other support systems during this time and for at least a few months after you quit.

This drug should not be taken if you have or have ever had:

  • Seizures (it can cause or worsen seizures)
  • Heavy alcohol use
  • Cirrhosis
  • Serious head injury
  • Bipolar (manic-depressive) illness
  • Anorexia or bulimia (eating disorders)

You also shouldn’t take it if you’re taking sedatives or have recently taken a monoamine oxidase inhibitor (MAOI, an older type of antidepressant).

The most common reported side effects of bupropion include dry mouth, trouble sleeping, tiredness, agitation, irritability, indigestion, and headaches. People using bupropion should call their doctors if they feel depressed or start thinking of suicide. They should also call their doctors for changes such as feeling anxious, agitated, hostile, aggressive, overly excited and hyperactive, confused, or unable to sleep. These are rare, but can happen, often near the start of treatment or after a dose change. Bupropion shouldn’t be used with certain other drugs, so tell all your doctors that you are taking it.

Combining bupropion and NRT for quitting smoking

Some doctors may recommend combination therapy for heavily addicted smokers, such as using bupropion along with a nicotine patch and/or a short-acting form of NRT (such as gum or lozenges). Combinations have been found to work better for some people than using any one part alone, but you should only use them together if your doctor is monitoring you.

Varenicline (Chantix)

Varenicline (brand name Chantix®) is a prescription medicine developed to help people stop smoking. It works by interfering with nicotine receptors in the brain. This means it has 2 effects: it lessens the pleasure a person gets from smoking, and it reduces the symptoms of nicotine withdrawal. Varenicline should be started a week before your Quit Day.

Several studies have shown taking varenicline can more than double the chances of quitting smoking when compared to taking no medicines at all. Some studies have also found it may work better than bupropion, at least in the short term.

Varenicline comes in pill form and is taken after meals, with a full glass of water. The daily dose increases over the first 8 days it’s taken. The dose starts at one 0.5 mg pill a day for the first 3 days, then the 0.5 mg pill twice a day for the next 4 days. At the start of the second week, the dose is raised to 1 mg in the morning and evening. For people who have problems with the higher dose, a lower dose may be used during the quit effort. Varenicline is given for 12 weeks, but people who quit during that time may get another 12 weeks of treatment to boost their chances of staying quit. Keep up with your other support systems during this time and for at least a few months after you quit.

Tell your doctor about any medical conditions and allergies before you start varenicline. Reported side effects have included headaches, nausea, vomiting, trouble sleeping, unusual dreams, gas, and changes in taste. People with heart disease may have a higher risk of heart attacks while on varenicline. There have also been reports of depressed mood, thoughts of suicide, attempted suicide, anxiety, panic, aggression, confusion, and other changes in behavior or mood in people taking varenicline. People who notice these problems should contact their doctors right away. Reports of these side effects have been rare, but can be serious when they do happen. Most people don’t have these emotional or behavioral problems while taking the drug.

Because of the reported side effects, some researchers have looked at people who were known to have depression before taking the drug. In those whose depression was well controlled, varenicline seemed to be safe. Studies are still underway on people with mental health or mood disorders. If you’ve ever had a mental health problem, discuss it with your doctor before starting this drug.

Combining varenicline and NRT or bupropion for quitting smoking

Not much research has been done to find out if varenicline is safe to use at the same time as nicotine replacement therapy (NRT). One study has suggested that using varenicline along with NRT is well-tolerated and safe, even though more people using both had side effects than those using only one. The company that makes varenicline had already noted that people who used the drug along with NRT had more side effects such as nausea and headaches. A 2013 study that compared varenicline plus a nicotine patch with varenicline plus a placebo patch showed no difference in quit rates, cravings, symptoms, or side effects.

Other researchers tested the use of varenicline along with bupropion. The group taking both drugs had more anxiety and depression than those on varenicline alone, and long term quit rates weren’t significantly higher. Research on combining drugs is ongoing.

“Off-label” prescription drugs to help smokers quit

For those who can’t use any of the FDA-approved drugs for helping smokers quit, or for those who have not been able to quit using them, other drugs have shown promise in research studies. They are recommended by the Agency for Healthcare Research and Quality for this kind of use, but have not been approved by the FDA for this purpose and so are used “off-label.” (See our document called Off-label Drug Use for more on this.) These drugs are only available with a prescription and are not recommended for pregnant smokers, teens, or people who smoke less than 10 cigarettes per day.


This is an older anti-depressant drug. When used in groups of smokers, it has been found to double the chances of success in quitting smoking when compared to those taking no medicine. It’s started 10 to 28 days before a person stops smoking to allow it to reach a stable level in the body.

Some people have side effects like a fast heart rate, blurred vision, trouble urinating, dry mouth, constipation, weight gain or loss, and low blood pressure when they stand up. The drug can affect a person’s ability to drive or operate machinery, and certain drugs cannot be used along with it.

If you and your doctor decide to use this drug, be sure your doctor and pharmacist know exactly what other drugs you’re taking before you start this medicine. Also be sure you know how to take it and how to taper it down when you are ready to stop. The dose of nortriptyline must be slowly lowered, since the drug cannot be stopped suddenly without the risk of serious effects. The drug must be used cautiously in people with heart disease. While you’re taking it, be sure to tell any doctor you visit that you are taking the drug.


Clonidine is another older drug. It’s FDA approved to treat high blood pressure. When used for smoking cessation, it can be given as a pill twice a day or as a once-a-week skin patch. In one study of heavy smokers who had failed in previous quit attempts, the group treated with clonidine was twice as likely to succeed in quitting smoking as the control group (which was given a fake pill) at the end of 4 weeks.

If you’re planning to use this drug, be sure your doctor and pharmacist know exactly what else you’re taking before you start taking it. The most common side effects of clonidine are constipation, dizziness, drowsiness, dry mouth, and unusual tiredness or weakness. There are rarely more severe side effects, such as allergic reactions, a slow heart rate, and very high or very low blood pressure. Your doctor may want to watch your blood pressure while you are on this drug. The drug can affect your ability to drive or operate machinery.

Clonidine can be started up to 3 days before you quit smoking, but can also be started the day you quit. It shouldn’t be stopped suddenly. The dose must be lowered over 2 to 4 days to prevent a rapid increase in blood pressure, agitation, confusion, or tremors.

Other drugs being studied to help smokers quit

Other medicines such as naltrexone, which comes as a pill, are being studied. It’s being used along with other treatments (like bupropion and NRT) to see if it can help reduce cravings. But the newest analysis of previous studies suggested it wasn’t helpful.

A drug called cytisine was recently tested in Poland and found to help reduce smoking. About 8% of smokers still didn’t smoke after a year, compared to about 2% of those on placebo. This drug is being studied in the United States, although most studies posted looked at rodents rather than people. Another drug being tested is sazetidine-A, but again, most published studies to date are on rodents.

Also still being tested are anti-smoking vaccines that are given as a series of shots.

Tests of these new treatments have been promising. So far they seem to be safe, but larger studies are needed to show these treatments work before the FDA can approve them for this use. Large studies of these treatments are now under way.

Last Medical Review: 02/06/2014
Last Revised: 02/06/2014