The correct answer is: D. Varenicline 0.5 mg PO once daily on days 1 to 3, followed by appropriate titration.

Option A would not be the best option. Though FDA approved for smoking cessation, Zyban® (bupropion SR) is a second line agent according to the ACC 2018 Expert Consensus Decision Pathway on Tobacco Cessation Treatment. In the EAGLES (Study Evaluating The Safety And Efficacy Of Varenicline and Bupropion For Smoking Cessation In Subjects With And Without A History Of Psychiatric Disorders) trial, bupropion was found to have a lower continuous quit rate compared to varenicline (16.2% and 21.8%, respectively). It may be an option for patients who are unable to take or were previously unsuccessful with a first-line option for smoking cessation but would not be an optimal agent for this patient as the combination of sertraline and Zyban® may increase the patient's risk of seizures and serotonin syndrome. For smoking cessation, the bupropion SR titration is 150 mg PO daily for 3 days then 150 mg PO twice daily for 3-6 months. The medication should be started 1-2 weeks prior to the quit date. Potential side effects include insomnia, agitation, dry mouth, and headache. Bupropion should not be used in a patient with a history of seizures as it lowers the seizure threshold.

Option B would not be the best option as nicotine replacement therapy (NRT) with one agent is a second-line therapy. In the EAGLES trial, varenicline was found to have higher rates of abstinence than monotherapy with nicotine patches (odds ratio [95% Confidence interval (CI)]: 1.74 [1.43 to 2.10]). Additionally, combination NRT was found to be more effective than a single type of NRT (risk ratio [95% CI]: 1.34 [1.18 to 1.51]). A single NRT product may be an option based on patient preference or if unable to tolerate combination NRT therapy. Dosing for the nicotine patch depends on the number of cigarettes a patient smokes daily. If a patient smokes 10 or more cigarettes/day, dosing would be as follows: 21 mg patch/day for 6 weeks followed by the 14 mg patch/day for 2-6 weeks then reduced to the 7 mg patch/day if the patient's cravings are controlled. Nicotine gum, nicotine lozenges, a nicotine inhaler, or nicotine nasal spray can be used in combination with the nicotine patch for combination NRT.

Nicotine gum and lozenges are both available over-the-counter in 2 mg and 4 mg doses. For both, patients should be started at the 4 mg dose if the patient smokes within 30 minutes of waking or the 2 mg dose if the patient smokes more than 30 minutes after waking. Patients should be instructed to chew the gum until their mouth tingles and then "park" the gum inside the cheek until the tingling fades. Patients should continue to "chew and park" and discard the gum after 30 minutes of use. One piece of gum can be used per hour (max 24 pieces/day). Nicotine lozenges should be placed between the cheek and gum and allowed to dissolve. Patients can use 1 piece every 1-2 hours (max 20 pieces/day). Potential side effects of the gum and lozenge include mouth irritation, heartburn, hiccups, and nausea.

Nicotine inhalers are available by prescription only and consist of a 10 mg/cartridge inserted into the inhaler device. Inhaler use entails puffing into the mouth or throat until cravings recede. One cartridge can be used every 1-2 hours and should be replaced with a new cartridge when the nicotine taste disappears (max 16 cartridges/day). Patients may experience mouth and throat irritation as well as coughing. Nicotine nasal spray (prescription only) is available in a 10 mL bottle that contains about 200 sprays (0.5 mg/spray). Patients should administer 1 spray to each nostril every 1-2 hours (max 80 sprays/day). Patients may experience nasal and throat irritation, rhinitis, and tearing. NRT should be continued for at least 3 months. NRT should be used on or after the patient's designated quit date.

Option C would not be the best option. Nortriptyline is a third line agent for smoking cessation in patients with cardiovascular disease and is not FDA-approved for smoking cessation. This would not be an optimal agent for this patient as the combination of nortriptyline and sertraline would increase the patient's risk for QTc prolongation and serotonin syndrome. For smoking cessation, nortriptyline is initiated at 25 mg daily 10 to 28 days before the quit date and titrated to 75-100 mg/day with continuation for 12 weeks or longer. It may be considered if first- and second- line agents have failed.

Option D is the best option. The ACC 2018 Expert Consensus Decision Pathway on Tobacco Cessation Treatment recommends either combination nicotine replacement therapy (nicotine transdermal patch and nicotine lozenge or gum or oral inhaler or nasal spray) or varenicline as a first-line option for smoking cessation in patients with stable cardiovascular disease in the outpatient setting. Previous case reports had reported negative neuropsychiatric effects with varenicline, but the black box warning for effects on mood, behavior or thinking was removed by the FDA in 2016. This was secondary to results from the EAGLES trial, which included psychiatric patients and did not result in a higher incidence of neuropsychiatric effects in psychiatric patients on varenicline versus nicotine replacement therapy or placebo. Thus, varenicline would be a reasonable option for this patient with stable major depressive disorder as well as safe to use with the current medication regimen. The varenicline titration is 0.5 mg once daily on days 1-3; 0.5 mg twice daily on days 4-7; 1 mg twice daily on day 8 until varenicline is stopped. Varenicline duration of use can range from 3-6 months. Of note, it is available as a starter pack (contains 11 tablets of 0.5 mg and 42 tablets of 1 mg). Varenicline should be started 1-4 weeks prior to the quit date though the quite date can be up to 3 months after starting the medication. Side effects to counsel the patient about include nausea, insomnia, vivid dreams, and headache.

References

1. Barua RS, Rigotti NI, 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;72:3332-65.
2. Anthenelli RM, Benowitz NL, West R, et al. Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial. Lancet 2016;387:2507-20.
3. Stead LF, Perera R, Bullen C, et al. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev 2012.
4. 2008 PHS Guideline Update Panel, Liaisons, and Staff. Treating tobacco use and dependence: 2008 update US Public Health Service Clinical Practice Guideline executive summary. Respir Care 2008;53:1217-22.
5. U.S. Food & Drug Administration. https://www.fda.gov/Drugs/DrugSafety/ucm532221.htm [Accessed 27 Feb 2019]