Grand Rounds August 8, 2025: Youth Nicotine Vaping Cessation: RCT of Varenicline Added to Remote Young Adult Lay Counselor Delivered Behavioral Cessation Support Vs. Texting Support (A. Eden Evins, MD, MPH)

Speaker

A. Eden Evins, MD, MPH
Cox Family Professor of Psychiatry, Harvard Medical School
Founding Director, MGH Center for Addiction Medicine
Director for Faculty Development, Mass General Hospital Department of Psychiatry

Keywords

Vaping; Nicotine; Cessation; Behavioral Support; Texting

Key Points

  • Vaping, though technically a less harmful alternative to cigarette smoking, is the primary route to nicotine addiction in youth. Initially promoted to help with smoking cessation, vaping devices are increasingly marketed towards young people and have transformed teen nicotine and cannabis use.
  • Few treatments for vaping cessation have been tested. The research team hypothesized that the pharmacotherapy varenicline could help young adults abstain from nicotine vaping.
  • They conducted a randomized clinical trial with 2 aims: evaluate the efficacy of varenicline in addition to behavioral support for cessation of vaped nicotine and assess the safety and tolerability of varenicline. The target population was adolescents attempting vaping cessation.
  • According to the original design, participants would be randomized to 1 of 2 arms: varenicline + behavioral therapy and placebo + behavioral therapy. The possibility arose that the behavioral intervention would be particularly effective, they wouldn’t be able to differentiate between the arms, and the trial would fail. So they added a third arm: a referral to a widely-available messaging app supporting youth vaping cessation.
  • The research team made a few additional modifications to cut costs and enhance adherence. These included fully remote intervention and assessment; non-clinical personnel delivering the behavioral interventions; and video documentation of adherence, with compensation of $1 per video.
  • Over half of participants offered varenicline + counseling quit vaping and were abstinent for the last 4 weeks of treatment. The 4-week abstinence rate was 14% in the placebo + counseling group and 6% in the group that received texting support.
  • The study had a 97% completion rate using remote methods for intervention delivery and data collection. The research team received video evidence for 52% of varenicline doses and 42% of placebo doses. Behavioral counseling attendance was higher in the varenicline group (84%) than in the placebo group (66%).
  • Nausea, vivid dreams, and insomnia were more common in the group that received varenicline.

Discussion Themes

There’s interest in testing the effectiveness of varenicline without the addition of behavioral support. It’s an important question, Dr. Evins noted, given that behavioral support can be hard to come by.

Varenicline has been associated with exacerbation of psychiatric symptoms, including suicidal ideation. However, this has not been replicated in large clinical trials or epidemiologic trials. Explanations for the association include the effects of nicotine withdrawal symptom or the manifestation of comorbid psychiatric illnesses.

Grand Rounds June 21, 2024: Efficacy and Safety of Electronic Cigarettes for Smoking Cessation: Keeping a Trial on a Polarizing Topic Running Under Regulatory and Epidemic Changes (Reto Auer, MD, MAS)

Speaker

Reto Auer, MD, MAS
Associate Professor in Primary Health Care, Head Substance Use Unit, Institute of Primary Health Care (BIHAM), University of Bern
Adjunct Physician, University Center for Primary Care and Public Health (Unisanté), Switzerland

Keywords

Smoking; cessation; e-cigarettes; nicotine

Key Points

  • For cigarette smokers who are struggling to quit, e-cigarettes may be a viable and less risky alternative. When it comes to smoking cessation, there is substantial evidence that nicotine e-cigarette usage increases quit rates compared to nicotine replacement therapies (NRTs). Because the nicotine is inhaled, rather than delivered more slowly by way of a patch or gum, e-cigarettes provide quick relief from cravings much in the way a traditional cigarette would.
  • E-cigarette use is a polarizing topic in the medical field. The somatic health risks posed by e-cigarettes are lower than that of conventional cigarettes. However, their addictive potential is similar. So, while the availability of e-cigarettes could substantially reduce the health risks of nicotine dependence for existing smokers, it poses a substantial risk of nicotine addiction to a new generation.
  • A study team led by Dr. Reto Auer ran a randomized clinical trial to assess the efficacy and safety of free e-cigarettes in addition to standard care vs standard care alone. Their secondary aim was to assess the effect of the intervention on respiratory symptoms.
  • 1,246 participants at five study sites in Switzerland were randomized at a 1:1 ratio to the control group (standard-of-care smoking cessation counseling, AKA SOC) and the intervention group (SOC + free e-cigarettes, along with advice on use of products). The intervention included a choice between 6 different aromas and 4 different nicotine concentrations. Researchers followed up with participants at 6-months (later extended to 12-, 24-, and 60 months).
  • At the end of the six months, the proportion of participants who reported zero tobacco use was 21% higher in the intervention group than in the control group; however, the percentage of participants in the intervention group who abstained from nicotine entirely altogether was almost 14% lower. In other words, the intervention group ended up smoking less tobacco, but consuming more nicotine. The intervention resulted in more adverse events but not more serious adverse events.
  • In conclusion, their study found that e-cigarette use plus standard counseling may be a viable option for tobacco smokers who want to abstain from smoking without necessarily abstaining from nicotine but may be less appropriate for those who want to abstain from both tobacco and nicotine.
  • Dr. Auer also discussed ethical considerations for the trial, namely the potential consequences if health care professionals were to state that e-cigarettes are less harmful that tobacco cigarettes. On the one hand, some smokers may quit smoking tobacco thanks to e-cigarettes; on the other hand, non-smokers may be more likely to use e-cigarettes and become addicted to nicotine as a result.

 

Discussion Themes

– There isn’t always heterogeneity in the products presently on the market. So, I have a little consternation about the devices that people are picking up in vape shops. Do you have any thoughts or comments on that? Of course, you need regulation. You cannot have a drug like this without oversight. I think in the U.S., you might be in a better place with FDA review. And there are now e-cigarettes [in the U.S.] that have been have gone through all the regulatory oversight… I’m completely with you, there’s a lot of research to be done before everyone can embrace recommending these.

From your perspective, how has the conversation about this trade off, this ethical balance that you described, evolved over time? Are you seeing movement, or do people tend to be entrenched in their positions? That question was at the core of our work. If you speak with some people in England, they say “Why do this trial? This is evident, you don’t need to.” But others will say “We will never allow e-cigarettes.” Our job was to be in the middle of it; to be the boring researchers who produced the evidence, who are not involved in the politics, and who try to understand the difference and see how the conversation moves.

– The trial focused on switching away from combustible cigarettes as opposed to nicotine cessation. As a physician, I would not want indefinite e-cigarette use for my patients. Do you think that was the optimal goal, or was it about what was feasible to achieve with a trial? Smoking is a chronic condition. As a clinician, how I translate this, is that the discussion is about shared decision making and your preference as a patient. If someone says, “I want to quit both [cigarettes and nicotine],” I’ll say, “Well, e-cigarettes might not be the best way.” But if someone says, “I don’t care about nicotine, I’ll be using nicotine for the rest of my life,” … At least they don’t smoke. The approach is different, and with e-cigarettes we can address a population we could never address before.

 

 

Tags

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