To Quit Smoking, Combination or Long-Duration Varenicline Is Not the Answer

Smoking has long been a leading cause of premature death. Fortunately, evidence-based behavioral therapy (such as counseling) and medication (such as nicotine chewing gum) can aid in smoking cessation.

Cigarette smoking causes over 480,000 premature deaths each year,[1] and 16 million Americans suffer from serious smoking-induced illnesses such as various cancers, emphysema, asthma and cardiovascular disease.[2]

Accordingly, a major goal of preventive medicine is to identify and successfully deploy strategies to assist individuals in overcoming their nicotine addiction and related dependence on cigarettes.

A recently published, well-designed clinical trial studied the combination therapy of varenicline (CHANTIX) and a nicotine patch (HABITROL, NICODERM CQ) as a method to quit smoking. The trial revealed that such combination therapy was no better than varenicline alone. It also failed to support the use of that drug beyond three months.

The randomized clinical trial[3]

The Oct. 19, 2021, issue of the Journal of the American Medical Association included an article describing a large, randomized, placebo-controlled clinical trial comparing the following four treatments:

(1) varenicline tablets (0.5 milligrams [mg] initially, increasing gradually to 1 mg, per day) for three months, which is the dosage and duration approved by the Food and Drug Administration (FDA)

(2) varenicline tablets plus nicotine patch (14 mg per day) for three months (FDA-approved nicotine patches are supposed to start with 21 mg or 14 mg per day for four to six weeks depending on the product and level of smoking, followed by tapering doses over 2 to 4 weeks before stopping)

(3) varenicline tablets for six months

(4) varenicline tablets plus nicotine patch for six months

A total of 1,251 subjects were randomly assigned in approximately equal numbers (ranging from 311 to 315) to each of the four groups. In addition to the above-described pharmacologic therapies, all subjects also received smoking-cessation counseling focused on medication use, support, coping and motivation. The trial was conducted from November 2017 to July 2019.

All 1,251 subjects smoked at least five cigarettes per day at the beginning of the trial, with an average consumption of 16 cigarettes per day. Just over half of these individuals were female and approximately one-quarter were Black. Their average age was 49 years, with an average smoking history of 28 years. Importantly, nearly 80% of the subjects had previously tried smoking-cessation medication.

Neither the subjects nor the researchers knew the group assignment of the subjects — a procedure known as double-blinding, which is intended to minimize the potential for bias. Such double-blinding was possible because of the use of placebo tablets and placebo patches for subjects not assigned to active treatment with these products.

The primary outcome was self-reported, past-seven-day smoking abstinence at the one-year mark following the initial quit target date. Carbon monoxide (CO) exhalation levels of less than 5 parts per million (ppm) were used to confirm smoking abstinence because higher residual levels of this toxic gas are a marker for recent smoking. Note that at the beginning of the trial the average CO exhalation level across all subjects was 17 ppm.

No statistically significant group differences in smoking cessation were observed across the four experimental groups. Specifically, the seven-day abstinence rates at one year for the three-month versus sixth-month varenicline groups were comparable (24.3% versus 24.8%, respectively), as were those for varenicline with versus without a nicotine patch (24.3% versus 24.8%, respectively). The researchers concluded that their findings do not support the use of long-duration varenicline or varenicline in combination with a nicotine patch as a method to quit smoking.

It should be noted that varenicline use is rarely associated with neuropsychiatric adverse effects, including changes in mood, depression, mania, psychosis, hallucinations, paranoia, delusions, aggression, anxiety and suicidal tendencies.[4] It also is commonly associated with nausea, vomiting, abnormal dreams, constipation and flatulence.

Additionally, the trial described above found that the combination of varenicline and nicotine patch significantly increased the incidence of skin rashes, itching or hives compared with varenicline alone. Such allergic skin reactions are known adverse effects of nicotine patches.[5]

What You Can Do

If you are a smoker and are trying to quit, avoid the use of varenicline and nicotine patches in combination as your therapy. In general, your initial attempts to quit smoking should involve counseling alone or combined with nicotine-replacement products (patches, gum or lozenges), but do not be discouraged if quitting is difficult and elusive.

Only use other medications, including bupropion (ZYBAN) and varenicline, after repeated failed attempts and under the continued and close supervision of a physician.
 

References

[1] Centers for Disease Control and Prevention. Tobacco-related mortality. April 28, 2020. https://www.cdc.gov/tobacco/data_statistics/fact_sheets/health_effects/tobacco_related_mortality/index.htm . Accessed April 7, 2022.

[2] Centers for Disease Control and Prevention. Office on Smoking and Health. Let’s Make the Next Generation Tobacco-Free: Your Guide to the 50th Anniversary Surgeon General’s Report on Smoking and Health. July 2015. https://www.hhs.gov/sites/default/files/consequences-smoking-consumer-guide.pdf. Accessed April 7, 2022.

[3] Baker TB, Piper ME, Smith SS et al. Effects of combined varenicline with nicotine patch and of extended treatment duration on smoking cessation: A randomized clinical trial. JAMA. 2021;326(15):1485-1493.

[4] Pfizer Inc. Label: varenicline (CHANTIX). February 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021928s048lbl.pdf. Accessed April 7, 2022.

[5] ALZA Corporation. Label: Nicotine transdermal system (NICODERM CQ). March 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/020165Orig1s047lbl.pdf. Accessed April 7, 2022.