Prescription medicines for quitting: varenicline, bupropion and cytisine

Two pills are approved by the US Food and Drug Administration (FDA) for quitting cigarettes, according to the CDC: varenicline and bupropion. Neither contains nicotine, and both need a prescription. A 2023 Cochrane network meta-analysis of 319 randomised trials estimated that varenicline led to eight additional quitters per 100 people (95% credible interval 6 to 10), compared with control, and bupropion to three additional quitters per 100 (2 to 4). This page sets out what the trials show for each medicine, including cytisine where the evidence exists, what official pages list as common side effects, and why a prescriber has to be involved. The related nicotine replacement therapy page covers the over-the-counter options.

How the two pills work

The CDC describes bupropion as a medicine with many effects on the brain, including decreasing craving and other nicotine withdrawal symptoms. Varenicline has two main effects, according to the CDC. It mimics some of nicotine's effects in parts of the brain, which reduces the urge to smoke and some withdrawal symptoms. It also attaches to the same brain sites that nicotine uses, without stimulating them as strongly, so nicotine from a cigarette has fewer places to attach and gives less of a buzz. For the underlying biology, see how nicotine dependence works.

What Cochrane found

The 2023 Cochrane network meta-analysis found high-certainty evidence that varenicline (odds ratio 2.33, 95% credible interval 2.02 to 2.68; 67 trials) and cytisine (2.21, 1.66 to 2.97; seven trials) were associated with higher quit rates than control, and so was bupropion (1.43, 1.26 to 1.62; 71 trials). An odds ratio above 1 favours the treatment. In absolute terms the review estimated eight extra quitters per 100 for varenicline, seven for cytisine and three for bupropion.

An earlier Cochrane overview of 12 reviews compared the medicines head to head. It found varenicline superior to bupropion (odds ratio 1.59, 1.29 to 1.96) and to single forms of nicotine replacement (1.57, 1.29 to 1.91), but not more effective than combination nicotine replacement (1.06, 0.75 to 1.48). Bupropion and nicotine replacement performed about equally (0.99, 0.86 to 1.13). The wider comparison of options is on quit methods compared.

Cytisine

The earlier Cochrane overview reported a risk ratio of 3.98 (95% interval 2.01 to 7.87) for cytisine against placebo, based on three trials with 2,151 participants, and noted that the largest of them was the oldest and least adequately conducted. The overview reported no significant adverse events or serious adverse events with cytisine. Regulatory status varies, and the 2023 Cochrane review notes that cytisine is not available in many countries. This site cannot say whether it can be prescribed where a reader lives.

What the EAGLES trial showed

Concerns had been raised about the neuropsychiatric safety of varenicline and bupropion, so a large trial called EAGLES tested the question directly. It randomised 8,144 smokers, with and without psychiatric disorders, at 140 centres in 16 countries to varenicline, bupropion, nicotine patch or placebo for 12 weeks, followed by 12 weeks without treatment. It was funded by Pfizer and GlaxoSmithKline, and the results were published in The Lancet in 2016.

Among people without a psychiatric disorder, moderate or severe neuropsychiatric events were reported by 1.3% on varenicline, 2.2% on bupropion, 2.5% on the patch and 2.4% on placebo. Among those with a psychiatric disorder the figures were 6.5%, 6.7%, 5.2% and 4.9%. The authors concluded there was no significant increase in neuropsychiatric events attributable to varenicline or bupropion compared with patch or placebo. On quitting, biochemically confirmed abstinence in weeks 9 to 12 was higher with varenicline than with placebo (odds ratio 3.61), patch (1.68) and bupropion (1.75). Mental health and quitting are explored further on quitting smoking and mental health.

Common side effects

For varenicline, the CDC lists nausea or vomiting, sleep problems including vivid dreams, and constipation or flatulence, with changes in mood or behaviour as rare. The NHS lists headaches, diarrhoea, heartburn, difficulty sleeping, dizziness and a bad taste in the mouth as common. In EAGLES, nausea was the most frequent adverse event on varenicline, at 25%.

For bupropion, the CDC lists nausea, dizziness, difficulty sleeping, constipation, dry mouth, rash, nervousness and difficulty concentrating, and a low risk of seizures, given as one person in a thousand. Cochrane's overview estimated about one seizure in 1,500, lower than expected. The 2023 review judged with moderate certainty that bupropion may slightly increase serious adverse events, by around one more person in 100, though the range included no difference.

Why a prescriber is needed

Both pills require a prescription, and both have conditions that call for a conversation first. The NHS says to tell a doctor before starting varenicline if you have kidney problems, have had heart problems or a seizure, are pregnant or breastfeeding, or have depression or another mental health condition. The CDC says bupropion cannot be used by people who have had bulimia or anorexia or a seizure disorder, or who take or recently stopped an MAO inhibitor medicine. Doctors also check other medicines for interactions.

The CDC and the NHS both say to stop and seek help promptly if hostility, agitation, low mood, suicidal thoughts or unusual changes in behaviour appear. The NHS advises calling 999 or going to A&E for thoughts of self-harm or a seizure. Doses and timing are set by the prescriber and the label, not this site. Support from a clinician or a quitline can sit alongside the medicine, as covered on counselling and quitlines.

The short version

Varenicline had the strongest results of the prescription pills, bupropion a smaller effect, and cytisine looks promising but is not available everywhere. Large trial data did not show a significant mental health signal, though official pages still list side effects to watch for. A prescriber should review pregnancy, heart disease, seizures, mental health conditions and other medicines before either pill is started.