First US trial of varenicline for vaping cessation successful

The first US clinical trial of varenicline for cessation of e-cigarette use shows promising results and warrants larger trials, researchers say.

Researchers from Yale Cancer Center and the Hollings Cancer Center at the Medical University of South Carolina published the results of their clinical trial of varenicline to help adults stop using e-cigarettes in the American Journal of Preventive Medicine.

The results showed a significant difference between the placebo group and the drug group. “We observed a 15% difference in the failure rate, with a 45% failure rate in the group receiving the drug,” said Lisa Fucito, Ph.D., lead author and director of tobacco treatment services at Yale Cancer Center and Smilow Hospital.

Benjamin Toll, Ph.D., director of the tobacco treatment program at MUSC Health and senior author of the study, said the researchers designed the trial to be as close to real-world conditions as possible, from the people participating in the trial to the type of support, which they are likely to receive from their general practitioners.

The publication of their results follows the publication of a trial of cytisinicline to stop e-cigarette use. Both drugs work similarly. However, varenicline is already available in the US market as generics, while cytisinicline has not yet received FDA approval and is currently not available to patients.

Varenicline, perhaps better known by the brand name Chantix, is approved by the FDA to help adults stop smoking regular cigarettes. But despite the growing number of people using e-cigarettes, there are no approved medication options to help them stop using e-cigarettes.

“People can get very high levels of nicotine exposure with these e-cigarette products and may use them almost constantly throughout the day. So the question we're all asking is, can any pharmacotherapy do the job?” - said Fuchito.

This is a matter of logistics. People who smoke cigarettes should take a cigarette out of the pack and light it. Easy to track usage. There are also natural stopping points - when a cigarette runs out, you need to put it out, and when the pack is finished, you need to throw it away and buy a new one before you start smoking again.

E-cigarettes, however, can last more than 5,000 puffs, making consumption difficult to track but easier to use. Toll said he has patients who describe keeping their e-cigarettes under their pillow so they can vape right before bed and immediately after waking up.

Previous studies have shown that most people who use e-cigarettes want to quit. But it was unclear whether products used to stop smoking regular cigarettes would work for e-cigarettes.

“We need more pharmacotherapeutic treatments to help manage the very strong physical dependence that can develop from using e-cigarettes. People experience significant withdrawal when they try to quit, and that withdrawal is so unpleasant and difficult to manage with behavioral support alone,” Fuchito said.

A recent Italian study combined pharmacotherapy with intensive weekly behavioral counseling sessions, and the cytisinicline trial also included weekly 10-minute sessions with trained counselors.

In this study, however, the researchers wanted to see how well pharmacotherapy might work in a typical healthcare setting - meaning that the patient would likely receive a brief discussion with a general practitioner, along with a prescription and information about stopping resources, but without subsequent consultations.

To recreate this, they developed a smoking cessation guide for patients with practical tools and tips for quitting. A licensed healthcare professional also met with each patient to explain how to use the drug, offer brief advice, and instruct them to set a discontinuation date of one to two weeks after starting the drug.

“We took a lighter approach to reflect the behavioral support you're likely to receive if you go to your doctor and ask for help stopping e-cigarette use,” Fuchito said.

The study also included patients with a history of depression. This was important because Chantix once had a "black box" warning following reports linking the drug to psychiatric side effects. That warning was lifted in 2016 after a very large study showed the drug was safe, but Toll and Fucito said the stigma of the warning remains in the minds of both medical professionals and the general public.

"There is still some hesitancy in prescribing this very safe - now generic - drug, and that shouldn't be the case," Toll said.

None of the participants in this study experienced serious side effects, although a larger study will be needed to confirm this finding. Most side effects were at the level of nausea, insomnia or vivid dreams.

Another good news is that those who stopped using e-cigarettes did not return to smoking regular cigarettes.

“If you have a history of smoking, one of the concerns in this area is that you will return to smoking when you stop using e-cigarettes,” Toll said. “And we didn’t find it.”

On the other hand, one potential problem the researchers identified in the results was that people without a history of smoking—in other words, those who have only ever used e-cigarettes—may have a harder time quitting. This may be due to the fact that this group is more likely to use e-cigarettes continuously throughout the day, thus getting more nicotine into their system.

Larger studies are needed to examine these issues. But this trial should at least give health care providers confidence in prescribing varenicline to patients trying to stop using e-cigarettes.

“We want people to turn to this drug again,” Fuchito explained. “There are people who need help now and who will likely struggle to stop using e-cigarettes on their own because technology allows nicotine to be used at levels we have never seen before.”