Key messages
· Varenicline can help people to stop smoking for at least 6 months. Evidence shows it works better than bupropion and using only one type of nicotine replacement therapy (e.g. only patches). Quit rates might be similar to using more than one type of nicotine replacement therapy at the same time (e.g. patches and gum together).
· Cytisine can help people to stop smoking for at least 6 months. It may work as well as varenicline, but future evidence may show that while it helps, it is not quite as helpful as varenicline.
· Future studies should test the effectiveness and safety of cytisine compared with varenicline and other stop-smoking medications, and should also investigate giving cytisine or varenicline at different doses and for different lengths of time.
What are ‘nicotine receptor partial agonists’?
Smoking tobacco is extremely bad for people’s health. For people who smoke, quitting is the best thing they can do to improve their health. Many people find it difficult to quit smoking. Nicotine receptor partial agonists (NRPAs) are a type of medication used to help people to stop smoking. They help to reduce the withdrawal symptoms people experience when they stop smoking, like cravings and unpleasant mood changes. They also reduce the pleasure people usually experience when they smoke. The most widely-available treatment in this drug type is varenicline. Cytisine is another, similar medication. They may cause unwanted effects such as feeling sick (nausea) and other stomach problems, difficulties sleeping, abnormal dreams, and headache. They may also lead to potentially serious unwanted effects, such as suicidal thoughts, heart problems and raised blood pressure.
What did we want to find out?
We wanted to find out if using NRPAs can help people to quit smoking, and if they cause unwanted effects. We wanted to know:
· how many people stopped smoking for at least 6 months; and
· how many people had unwanted effects.
What did we do?
We searched for studies that investigated NRPAs used to help people quit smoking. People in the studies had to be chosen at random to receive an NRPA, or another NRPA, placebo (medication like the NRPA but with no active ingredients) or no treatment. They had to be adult tobacco smokers who wanted to stop smoking.
What did we find?
We found 75 studies that compared NRPAs with:
· placebo or no medicine;
· nicotine replacement therapy, such as patches or gum;
· bupropion (another medicine to help people stop smoking);
· another NRPA;
· e-cigarettes.
The USA hosted the most studies (28 studies). Other studies took place in a range of countries across the world, some in several countries.
Main results
People are more likely to stop smoking for at least six months using varenicline than using placebo (41 studies, 17,395 people), bupropion (9 studies, 7560 people), or just one type of nicotine replacement therapy, like patches alone (11 studies, 7572 people). They may be just as likely to quit as people using two or more kinds of nicotine replacement therapy, like patches and gum together (5 studies, 2344 people).
Cytisine probably helps more people to stop smoking than placebo (4 studies, 4623 people) and based on studies that compared cytisine with varenicline (2 studies, 2131 people), there may be a benefit from varenicline for quitting smoking, however further evidence could strengthen this finding or show a benefit from cytisine.
For every 100 people using varenicline to stop smoking, 21 to 25 might successfully stop, compared with only 18 of 100 people using bupropion, 18 of 100 people using a single form of nicotine-replacement therapy, and 20 of 100 using two or more kinds of nicotine-replacement therapy. For every 100 people using cytisine to stop smoking, 18 to 23 might successfully stop.
The most common unwanted effect of varenicline is nausea, but this is mostly at mild or moderate levels and usually clears over time. People taking varenicline likely have an increased chance of a more serious unwanted effect that could result in going to hospital, however these are still rare (2.7% to 4% of people on varenicline, compared with 2.7% of people without) and may include many that are unrelated to varenicline. People taking cytisine may also have a slightly increased chance of serious unwanted effects compared with people not taking it, but this may be less likely compared with varenicline.
What are the limitations of the evidence?
The evidence for some of our results is very reliable. We’re very confident that varenicline helps people to quit smoking better than many alternatives. We’re less sure of some other results because fewer or smaller studies provided evidence.
Several results suggest one treatment is better or less harmful than another, but the opposite could still be true.
How up to date is the evidence?
The evidence is up to date to 29 April 2022.