A large review compared the effectiveness of methods to quit smoking, with three emerging as clear winners for helping people kick the habit.

The medications varenicline and cytisine, as well as nicotine e-cigarettes proved to be the most successful among the interventions reviewed by a UK team.

A total of 157,179 smokers were included in the analysis of 319 randomized controlled trials (RCTs), that tracked success in quitting for at least six months.

"The best thing someone who smokes can do for their health is to quit smoking," says public health scientist Jamie Hartmann-Boyce, at the time from the University of Oxford.

"Smoking remains the leading cause of preventable disease and death worldwide, and though many people want to quit smoking, it can be hard to do so."

The main addictive ingredient, nicotine, is one of the most widely used substances and the third most addictive, exerting a powerful grip on brains. The data showed that without assistance, only about 6 in 100 people have a chance of successfully quitting.

Varenicline and cytisine work by activating brain nicotinic receptors – which release dopamine when activated by nicotine – and preventing nicotine from activating them.

There was no significant difference in the effectiveness of cytisine (brand name Tabex) and varenicline (brand names Chantix and Champix), and nicotine e-cigarettes. According to the findings, about 14 percent of smokers who try to quit with the help of these methods will be successful for six months or longer.

The next most effective strategy was to combine two kinds of nicotine replacement therapy (NRT), such as nicotine patches and gum or lozenges.

"However, using a single form of NRT, like the patch or gum alone, resulted in fewer additional quitters," says University of Oxford medical scientist Nicola Lindson.

"Around 12 in 100 people using two forms of NRT together will quit successfully, compared to around 9 in 100 people using only one type."

Gradually reducing nicotine may be slightly more effective than quitting abruptly, the data showed. Whether someone starts nicotine treatment before or after quitting, and the dose taken, doesn't seem to affect efficacy.

Another medication called bupropion (brand name Wellbutrin), showed effectiveness in 9 percent of quitters.

The data on safety found that bupropion might have a very small increase in serious adverse events compared to not using any medication. In general, the treatments studied were safe, with few severe side effects, though the authors note that not all the RCTs included data on side effects.

"Pooling together all of the available trials comparing smoking cessation medications with control interventions is a really important way in which we can assess what works to help people quit smoking," says social scientist Caitlin Notley from the UK University of East Anglia, in an expert reaction.

"This network meta-analysis shows that e-cigarettes, varenicline and cytisine are all effective smoking cessation aids. Twice as many people managed to quit smoking using one of these aids compared to control conditions."

The authors don't think more evidence will change the clear results, though more data in terms of side effects and the best combinations of medications and behavioral support, would be helpful.

Like the majority of research, most studies were conducted in countries with higher incomes, so evidence from lower-income countries is scarce. The team hopes future studies will look at how socioeconomic status affects quitting smoking.

"It is very difficult to quit. There are several products available to help with this, but the relative effectiveness of these methods has long been uncertain," Lindson says.

"Our research dives deep into the world of smoking cessation… providing people who smoke, healthcare professionals and policymakers with reliable data to make informed decisions."

The study has been published in the Cochrane Database of Systematic Reviews.