A new joint US Department of Veterans Affairs and US Department of Defense clinical practice guideline broadens treatment recommendations for tobacco and nicotine dependence while extending treatment to patients who are not ready to quit.
A multidisciplinary work group of 21 US Department of Veterans Affairs (VA) and US Department of Defense (DoD) experts developed 19 key questions addressing tobacco and nicotine treatment in military service members and veterans. In a systematic review, they assessed 952 full-text articles published between 2014 and 2024, with 109 studies ultimately included in the evidence base. The work group used the GRADE framework and considered evidence quality, benefits and harms, patient and clinician preferences, and feasibility when determining recommendation strength.
The guideline included 32 recommendations across 10 topic areas, with complete abstinence from tobacco or nicotine as the primary desired outcome. The work group prioritized biochemically verified long-term abstinence of at least 6 months, preferably 12 months when available, while also considering self-reported abstinence, quit attempts, and safety.
For combustible tobacco cessation, the guideline strongly recommended US Food and Drug Administration–approved nicotine replacement therapy (NRT), bupropion sustained release, or varenicline. Pharmacotherapy may have doubled to tripled abstinence rates compared with placebo. The guideline strongly recommended varenicline monotherapy over bupropion or single-agent NRT based on high-certainty evidence from 20 randomized controlled trials. No statistically significant difference in abstinence was identified between varenicline and combination NRT, although direct comparisons were limited.
Combination NRT was strongly recommended over NRT monotherapy. Sixteen trials involving more than 12,000 participants provided high-certainty evidence that combining a nicotine patch with a short-acting NRT product improved abstinence compared with a single NRT product. Higher-dose nicotine gum and patches also resulted in greater treatment success comapred with lower-dose formulations.
Among patients who are not ready to quit within the next 30 days, the guideline weakly recommended either NRT or varenicline. Across 7 randomized controlled trials, NRT increased quit attempts but did not improve abstinence compared with no treatment or brief intervention. Varenicline was supported by 2 randomized controlled trials and a separate trial of 1,510 participants in which 24 weeks of treatment improved quit attempts and abstinence compared with placebo.
The guideline strongly recommended varenicline to increase abstinence from smokeless tobacco and weakly recommended NRT. For electronic nicotine delivery systems (ENDS), either varenicline or NRT was weakly recommended. A systematic review involving 3 randomized controlled trials with 184 participants favored varenicline for ENDS cessation compared with placebo. Evidence supporting NRT was rated very low because of small samples and other limitations.
The guideline also weakly recommended immediate retreatment with pharmacotherapy and counseling following a return to tobacco use. No studies directly evaluated treatment following confirmed abstinence and subsequent relapse. Evidence instead came from trials using broader eligibility criteria, including those recycling or reengaging patients in cessation treatment who reported higher abstinence with retreatment but were rated as poor to fair quality.
Among patients with stable mental health conditions, the guideline weakly recommended pharmacotherapy for tobacco cessation. Evidence included a randomized controlled trial of more than 8,000 participants, more than half of whom had psychiatric disorders. Varenicline produced greater abstinence than nicotine patch, bupropion, or placebo, while nicotine patch and bupropion were more effective than placebo. The trial found no increased neuropsychiatric effects with varenicline or bupropion compared with nicotine patch or placebo. The guideline weakly recommended concurrent behavioral treatment and pharmacotherapy for tobacco cessation among patients receiving treatment for alcohol or other substance use disorders.
In an accompanying editorial, Michael B. Steinberg, MD, MPH, and Lauren R. Pacek, PhD, of Rutgers Robert Wood Johnson Medical School, highlighted the recommendations supporting combination NRT, varenicline, and treatment among patients not yet ready to quit. They noted that the guideline gave limited attention to relative risk and the continuum of harm among tobacco and nicotine products, particularly in its weak recommendation against using ENDS as a smoking cessation treatment. The editorialists argued that emerging evidence regarding ENDS and smoking cessation warranted consideration when discussing harm reduction.
The guideline had several limitations. Evidence quality varied across recommendations, ranging from multiple meta-analyses for some interventions to only 1 or a few randomized controlled trials for others. Much of the evidence was derived from civilian populations, requiring extrapolation to military service members and veterans. Evidence was particularly limited for newer nicotine products, and the work group identified additional research needs involving ENDS, nicotine pouches, polyproduct use, active-duty populations, and direct comparisons of pharmacotherapy combinations.
“Clinical practice guidelines are intended to promote the delivery of evidence-based care while allowing flexibility for individual clinical judgment and patient preferences,” wrote Mark G. Myers, PhD, of the VA San Diego Healthcare System and University of California, San Diego School of Medicine, and colleagues.
Full disclosures of the authors can be found in the published articles.
Source: Annals of Internal Medicine, Editorial, Patient Summary