guidelines smoking cessation meds

The American thoracic Society just published guidelines for medications to help with smoking cessation, strongly supporting the primary use of varenicline (see smoking cessation ATS guidelines2020 in dropbox, DOI: 10.1164/rccm.202005-1982ST, or https://www.atsjournals.org/doi/pdf/10.1164/rccm.202005-1982ST )

 

Recommendations: medications for tobacco-dependent adults

 

1. varenicline is recommended over nicotine patch (strong recommendation, moderate certainty in the estimated effects)

    -- 14 RCTs: varenicline had a 20% increased likelihood of seven-day abstinence at 6 months follow-up, RR 1.20 (1.09-1.32), absolute risk reduction 40 more per 1000 patients; also more effective during the treatment period Itself

    -- varenicline also had a slightly lower risk of serious adverse effects vs nicotine patch, 3 fewer per 1000 patients

    -- though the cost of varenicline is about 8 times higher than the patch, cost-effective analysis favored varenicline

 

2. varenicline is recommended over bupropion (strong recommendation, moderate certainty in the estimated effects)

    -- 7 RCTs: 30% increase in tobacco abstinence in seven-day point prevalence at 6 months, RR 1.30 (1.19-1.42), absolute risk reduction of 147 more per 1000 patients; also more effective during the treatment period itself

    -- serious adverse effects seem to be decreased with varenicline over bupropion

    -- varenicline also was cost-effective as compared to generic bupropion

 

3. varenicline plus nicotine patch recommended over varenicline alone (conditional recommendation, very low certainty in the estimated effects)

    -- though it is counterintuitive that this combination would be effective (varenicline acts as a nicotinic acetylcholine receptor agonist-antagonist), nicotine addiction is likely to be more complex than that

    -- 3 treatment trials comparing varenicline with varenicline plus nicotine patch: 36% benefit for the combo in seven-day point prevalence abstinence at 6 months, RR 1.36 (1.07-1.72), absolute risk reduction of 105 more per 1000 patients; also decreased smoking during the treatment period itself

    -- trivial increase in serious adverse effects by the combination

    -- this was considered a conditional recommendation because of serious imprecision related to a very small number of events

    -- the combination therapy may be more acceptable if introduced sequentially

 

4. varenicline is recommended over electronic cigarettes (conditional recommendation, very low certainty in the estimated effects)

    -- only one observational study, network meta-analysis done: though shaky evidence, varenicline probably did better in smoking cessation

    -- varenicline probably had fewer serious adverse effects

    -- and concern was raised about new evidence that was not included in this evaluation, indicating deaths or disability due to electronic cigarette/vaping associated lung injury, burns during product explosion, acute nicotine poisoning, and seizures, and that this recommendation would be reevaluated if there continued to be such reports

 

5. for people who are not ready to stop tobacco, varenicline treatment is still recommended over waiting until the patients are ready to stop tobacco use (strong recommendation, moderate certainty in its estimated effects)

    -- the basis of this argument is that behavior change seems to be more dynamic than the old model of behavior change, a significant number of patients undergo unplanned cessation attempts, some suggestive data that pretreatment of tobacco users might increase the number of patients who stop smoking, and that patients who do not seem ready to abstain may be willing to try to tobacco-dependence treatment. The concept is that pharmacotherapy is a therapeutic intervention aimed at improving readiness to stop smoking

    -- 5 trials: twice as many were able to stop smoking using the seven-day point prevalence of abstinence at 6 months, RR 2.00 (1.70-2.35), 173 more were able to quit per 1000 patients; and more were able to quit during the study itself

    -- serious adverse effects were likely increased with varenicline

    -- cost-effective analysis favored intervention

    -- the authors also suggest that providers no longer consider the only goal to be smoking cessation, but also an increased willingness to consider an abstinence attempt; also, cessation rates steadily increased  through the 24 weeks of pretreatment, suggesting that attempts to set a “quit date” too early in treatment may be counterproductive

 

6. in those with comorbid psychiatric conditions, including substance use disorder, depression, anxiety, schizophrenia, and/or bipolar disorder, clinicians should start with the optimal medication for the patient without psychiatric conditions

    -- although varenicline did have a black box warning of serious neuropsychiatric side effects, this was rescinded by the FDA. The concern was neuropsychiatric adverse effects found in post-market surveillance, though in the RCTs there was no increase even in those with preexisting mental illness

    --overall, studies have found the following: those with psychiatric conditions are more likely to be tobacco users (30%) and overall less likely to quit smoking with meds (though in 2 RCTs varenicline was better than nicotine patch in people with mental illness), no clear relationship between varenicline on the use of substances in those with substance use disorders, there is little evidence suggesting neuropsych serious adverse effects from varenicline even in those with preexisting mental health issues, but those with psych illness are less likely to get evidence-based meds for smoking cessation.

 

7. extended duration (>12 weeks) treatment is recommended over standard duration (6-12 weeks), (strong recommendation, moderate certainty in the estimated effects)

    --12 RCTs comparing standard vs extended duration of meds: 22% increased 7-day point prevalence of abstinence at 1 year, RR 1.22 (1.07-1.30), with 53 more able to quit per 1000 patients

    --serious adverse effects probably slightly more with extended therapy

    --extended treatment is cost-effective

    --the recommended timecourse is not specified, but “the panel made a strong recommendation for extended-duration treatment of tobacco dependence beyond 3 months, including regimens of up to 12 months in duration” and the balance of effect outweighs its higher price (3 months of varenicline costs $1220-$1584). Other societies (eg Am College of Cardiol) suggest 3-6 months for varenicline or bupropion

 

Commentary:

-- the real changes in this recommendation over prior ones are: dramatic preference for varenicline over other initial therapies, with the potential benefit of simultaneous nicotine patches; the focus on discussing starting therapy even in those who do not feel they are ready to quit; and no difference in choice of varenicline if underlying neuropsych disorder or substance use disorder

--the likelihood of pharmacotherapy leading to tobacco cessation is on the order of 308 additional people per 1000 smokers

--there are many, many studies on the importance of smoking cessation, with several finding that smoking is the single most important cardiac risk factor and the highest benefit from any single intervention would be from smoking cessation

    --smoking even 1 cigarette/d is still associated with ½ the cardiac risk of smoking 20/day: http://gmodestmedblogs.blogspot.com/2018/01/smoking-just-one-cigarette-one-too-many.html

 --relevant prior blogs on smoking (there are lots…)

    --for the benefit of varenicline for almost-ready smokers: http://gmodestmedblogs.blogspot.com/2015/02/varenicline-for-almost-ready-smoker.html

    --for one on smoking cessation meds in those with psych disorders: http://gmodestmedblogs.blogspot.com/2016/04/smoking-cessation-meds-in-pts-with.html

    --one suggesting that pretreatment with nicotine patch by 2 weeks improves quit rates: http://gmodestmedblogs.blogspot.com/2016/03/abrupt-vs-gradual-smoking-cessation.html

 

limitations:

-- most of the cost-effective analyses were done by the drug companies

-- recommendations are only for meds, and no consideration (or even mention) of other therapies: behavioral changes, etc

    -- and, no specifics of risk stratification: are there subgroups of patients who respond differently to different meds, or different nonpharmacologic approaches? for example, bupropion is a pretty great drug for depression. and underlying depression is likely for many patients to be a less-motivator to stop smoking. would be interesting to have an actual RCT comparing varenicline vs bupropion (perhaps with counseling) in those with varying degrees of depression

-- there are impressive studies in the past showing that bupropion plus nicotine patches works better than bupropion alone. is varenicline better than that combo??  is the combo of varenicline plus patches better than bupropion plus patches?? i have not seen any of these studies, and this lacune in our knowledge may be a very important one, especially in light of the benefits of bupropion in those with depression

so, these guidelines represent quite a shift to varenicline, varenicline, varenicline. i would still treat depressed smoking patients preferentially with bupropion, and preferentially in combination with nicotine patchs/gum to improve the chances of smoking cessation (with counseling for depression, per patient wishes) as my first line therapy. and, if prescribing varenicline in those with underlying psych issues, i would still check-in more frequently with them: there are still increased reported problems with sleep, weird dreams, sleep walking, along with the reports of agitation in the past, all of which can exacerbate many underlying psych problems. so, i am still concerned despite the reassurances by the above studies, which are pretty much all drug-company sponsored. but this guideline and their literature assessment definitely increases varenicline's stature as overall first line drug, with perhaps adding nicotine patches if needed. 

geoff

 

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