A new review provides some answers to that question. A multinational review including participation from the University of Massachusetts Amherst suggests that nicotine electronic cigarettes (e-cigarettes) and two prescription medications that curb symptoms of withdrawal work best for helping smokers quit.
In a report in the Cochrane Database of Systematic Reviews, the researchers advised that dual forms of nicotine replacement therapy (NRT), such as combining a patch with gum or a lozenge, appear to be nearly as effective.
“The best thing someone who smokes can do for their health is to quit smoking,” said senior author Jamie Hartmann-Boyce, PhD, assistant professor of health policy and management in the School of Public Health and Health Sciences at the University of Massachusetts (UMass) Amherst. “Our findings provide clear evidence of the effectiveness of nicotine e-cigarettes and combination nicotine replacement therapies to help people quit smoking. The evidence also is clear on the benefits of medicines cytisine and varenicline, but these may be harder for some people to access at the moment.”
The research was conducted at the University of Oxford in the United Kingdom.
“Tobacco smoking is the leading preventable cause of death and disease worldwide. Stopping smoking can reduce this harm and many people would like to stop,” the authors write. “There are a number of medicines licensed to help people quit globally, and e-cigarettes are used for this purpose in many countries. Typically, treatments work by reducing cravings to smoke, thus aiding initial abstinence and preventing relapse.”
Noting that more information on comparative effects of these treatments is needed to inform treatment decisions and policies, the study team sought to investigate the comparative benefits, harms, and tolerability of different smoking cessation pharmacotherapies and e-cigarettes when used to help with smoking cessation.
The study team identified studies from recent updates of Cochrane Reviews investigating interventions of interest. They then updated the searches for each review using the Cochrane Tobacco Addiction Group specialized register to April 29, 2022.
Of the 332 eligible randomized control trials (RCTs), 319 (including 835 study arms and 157,179 participants) provided sufficient data to be included in the review.
The researchers reported that they found high-certainty evidence that nicotine e-cigarettes (odds ratio [OR] 2.37; 95% CrI [credibility interval], 1.73-3.24; 16 RCTs; 3,828 participants), varenicline (OR 2.33; 95% CrI, 2.02-2.68; 67 RCTs; 16,430 participants) and cytisine (OR 2.21; 95% CrI, 1.66-2.97; seven RCTs; 3,848 participants) were associated with higher quit rates than control.
“In absolute terms, this might lead to an additional eight (95% CrI, 4-13), eight (95% CrI, 6-10) and seven additional quitters per 100 (95% CrI, 4-12), respectively,” the researchers explained. “These interventions appeared to be more effective than the other interventions apart from combination NRT (patch and a fast-acting form of NRT), which had a lower point estimate (calculated additive effect) but overlapping 95% CrIs (OR 1.93; 95% CrI, 1.61-2.34).”
The study also identified high-certainty evidence that nicotine patch alone (OR 1.37; 95% CrI, 1.20-1.56; 105 RCTs; 37,319 participants); fast-acting NRT alone (OR 1.41; 95% CrI, 1.29-1.55; 120 RCTs; 31,756 participants); and bupropion (OR 1.43; 95% CrI, 1.26-1.62; 71 RCTs; 14,759 participants) were more effective than control, resulting in two (95% CrI, 1-3); three (95% CrI, 2-3); and three (95% CrI, 2-4) additional quitters per 100, respectively.
“Nortriptyline is probably associated with higher quit rates than control (OR 1.35; 95% CrI, 1.02-1.81; 10 RCTs; 1,290 participants; moderate-certainty evidence), resulting in two (CrI 0-5) additional quitters per 100,” the authors wrote. “Non-nicotine/placebo e-cigarettes (OR 1.16, 95% CrI; 0.74-1.80; eight RCTs; 1,094 participants; low-certainty evidence), equating to one additional quitter (95% CrI, –2 to 5), had point estimates favoring the intervention over control, but CrIs encompassed the potential for no difference and harm.”
In addition, the study stated, “There was low-certainty evidence that tapering the dose of NRT prior to stopping treatment may improve effectiveness; however, 95% CrIs also incorporated the null (OR 1.14; 95% CrI, 1.00-1.29; 111 RCTs; 33,156 participants). This might lead to an additional one quitter per 100 (95% CrI, 0-2).”
Few adverse effects were identified, although the researchers posit that bupropion might present slightly higher risks.
“The most effective interventions were nicotine e-cigarettes, varenicline and cytisine (all high certainty), as well as combination NRT (additive effect, certainty not rated),” the authors concluded. “There was also high-certainty evidence for the effectiveness of nicotine patches, fast-acting NRT and bupropion. Less certain evidence of benefit was present for nortriptyline (moderate certainty), non-nicotine e-cigarettes and tapering of nicotine dose (both low certainty).”
“Our research dives deep into the world of smoking cessation,” lead author Nicola Lindson, PhD, pointed out. “By pulling together this data, we can see that when people use the medicines licensed for quitting smoking or nicotine e-cigarettes, they are more likely to quit than if they do not use these aids.”
Dr. Hartmann-Boyce explained that while the long-term effects of using nicotine e-cigarettes are not known, the team reviewed were testing regulated nicotine-containing e-cigarettes without additional additives known to cause harm. “Nicotine itself is not the thing that causes the many diseases we associate with smoking,” she advised. “Broad scientific consensus is that regulated nicotine e-cigarettes are highly, highly likely to be much less harmful than conventional cigarettes, but not harmless.”
A UMass Amherst press release noted that the brand-name form of varenicline—Champix—is not available in the United States and other parts of the world due to a manufacturing problem, though generic forms of varenicline have been approved by the FDA. Cytisine is not currently licensed or marketed in the U.S. and most other countries outside of Central and Eastern Europe, it added.
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