Kicking the Habit With Combination Therapy: Updates in Tobacco Cessation Treatment

Tobacco use is the leading preventable cause of death in the United States and causes 1 out of every 6 deaths in the United States each year.¹ In 2018, nearly 14 of every 100 (13.7%) US adults aged 18 years or older currently* smoked cigarettes.² Smoking also causes premature death, as the life expectancy for a smoker is at least 10 years shorter than for a nonsmoker.³

As pharmacists, we often educate our patients about the harms of tobacco use and the benefits they can experience from quitting. Smokers who quit before the age of 40 reduce their risk of death from a smoking-related disease by 90%.³

But how can we as pharmacists help patients have the most successful quit attempt? Addressing the physiological addiction to nicotine and the behavioral habit of using tobacco is key. The Treating Tobacco Use and Dependence: 2008 Update recommends offering all smokers medications in combination with behavioral counseling.⁴

The guidelines recommend all 7 of the FDA-approved medications for treating tobacco use (bupropion, varenicline, nicotine patch, nicotine gum, nicotine lozenge, nicotine inhaler, and nicotine nasal spray) and states that there is no algorithm to guide optimal selection. As medication experts, we are able to interview patients and decipher what may be the best option for them, but what about patients who may benefit from using 2 products to achieve success?

The 2008 guidelines briefly mention the use of combination therapy for patients who are highly dependent on nicotine or have a history of withdrawal.⁴ These guidelines specifically outline using combination nicotine replacement therapy (NRT), or the patch, in combination with bupropion and have no mention of using varenicline for patients who may need combination therapy.

The American College of Cardiology released an Expert Consensus Decision Pathway on Tobacco Cessation Treatment in 2018, in which combination treatment is discussed.⁵ For outpatient treatment of tobacco dependence, patients with stable CVD can use a combination of varenicline and NRT, varenicline and bupropion, or bupropion and NRT, if a single agent is insufficient. A smaller body of evidence supports these combinations; however, these combinations are tolerable to patients and they generated promising efficacy data. With the addition of these guidelines, a new option to use varenicline in combination with other smoking cessation products is available.

Chang and colleagues conducted a systematic review and meta-analysis of 3 randomized controlled trials that looked at the safety and efficacy of varenicline in combination with nicotine patches compared with varenicline alone for smoking cessation in 904 participants.⁶

Combination varenicline and patch increased abstinence rates (44.4% vs. 35.1%, OR=1.50, 95% CI 1.14 to 1.97) and was more effective at 6 months when the patch was used with varenicline before the quit date. Adverse events between the placebo and nicotine patch combined with varenicline were not clinically significant.

Vogeler and colleagues explored another option for combination treatment.⁷ The authors conducted a systematic review of 4 trials that examined the safety and efficacy of varenicline in combination with bupropion for smoking cessation in 1193 participants. The authors concluded that combination therapy of varenicline and bupropion was an effective and safe treatment option.

However, statistical analysis was not conducted in this systematic review. Two of the trials were open-label and 1 was retrospective. The well-designed trial found the combination of varenicline and bupropion to be significantly more effective than varenicline in male smokers (OR=4.26, 95% CI 1.73 to 10.49) and in smokers with a high level of nicotine dependence, defined as a score >5 on the Fagerström Test for Nicotine Dependence (OR=3.51, 95% CI 1.64 to 7.51).⁸ Interestingly, adding bupropion to varenicline did not mitigate weight gain.

Combination therapy with varenicline is likely to benefit patients who have previously failed nicotine replacement, who are highly dependent smokers or experience withdrawal symptoms with monotherapy.^4,5,9,10 The overall decision on which combination therapy to use to treat tobacco dependence should be individualized based on the patient’s preference, previous quit attempts, drug interactions, and insurance coverage. It is important to remember that these interventions should be accompanied by behavioral counseling to ensure patients have the most successful quit attempt.

On January 23, 2020, the US Surgeon General released a report on smoking cessation, the first such report on smoking in 30 years.¹¹ This expands on the findings of a 1990 report and explores the many benefits regarding smoking cessation.

The report also discusses the role of the health care team in promoting cessation and highlights pharmacists as a part of this team. As one of the most visible members of the health care team, pharmacists are uniquely positioned to assist and support patients in tobacco cessation.

This assistance and support may vary in content depending on the practice site and can be as simple as providing the patients with online resources or be as in-depth as giving medication recommendations in combination with behavioral support. Continuing to adequately treat tobacco dependence, pharmacists are saving lives.

References

• U.S. Department of Health and Human Services. The Health Consequences of Smoking: 50 Years of Progress. A Report of the Surgeon General. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2014.
• Creamer MLR, Wang TW, Babb S, et al. Tobacco Product Use and Cessation Indicators Among Adults - United States, 2018. Centers for Disease Control and Prevention. https://www.cdc.gov/mmwr/volumes/68/wr/mm6845a2.htm?s_cid=mm6845a2_w. Published November 15, 2019. Accessed January 31, 2020.
• Jha P, Ramasundarahettige C, Landsman V, et al. 21st-century hazards of smoking and benefits of cessation in the United States. N Engl J Med. 2013;368(4):341-50.
• Tobacco Use and Dependence Guideline Panel. Treating Tobacco Use and Dependence: 2008 Update. Rockville (MD): US Department of Health and Human Services; 2008 May. https://www.ncbi.nlm.nih.gov/books/NBK63952/ Accessed October 1, 2019.
• Barua RS, Rigotti NA, Benowitz NL, et al. 2018 ACC Expert Consensus Decision Pathway on Tobacco Cessation Treatment: A Report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol. 2018;72(25):3332-3365.
• Chang PH, Chiang CH, Ho WC, Wu PZ, Tsai JS, Guo FR. Combination therapy of varenicline with nicotine replacement therapy is better than varenicline alone: a systematic review and meta-analysis of randomized controlled trials. BMC Public Health. 2015; 15:689.
• Vogeler T, Mcclain C, Evoy KE. Combination bupropion SR and varenicline for smoking cessation: a systematic review. Am J Drug Alcohol Abuse. 2016;42(2):129-139.
• Rose JE, Behm FM. Combination treatment with varenicline and bupropion in an adaptive smoking cessation paradigm. Am J Psychiatry. 2014; 171:1199-1205.
• Ebbert JO, Hays JT, Hurt RD. Combination pharmacotherapy for stopping smoking: what advantages does it offer? Drugs. 2010;70(6):643-650.
• Siu AL. Behavioral and Pharmacotherapy Interventions for Tobacco Smoking Cessation in Adults, Including Pregnant Women: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2015;163(8):622-34.
• U.S. Department of Health and Human Services. Smoking Cessation. A Report of the Surgeon General. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2020.