#27 Pharmacotherapy for Smoking: Which work and what to consider (Part II)?
CLINICAL QUESTION
In patients ready to make a smoking cessation attempt, how effective are registered first-line medications and what are the potential concerns?
BOTTOM LINE
Bupropion, nortriptyline and varenicline are all effective in smoking cessation, with varenicline more-so. Adverse events vary and may in part relate to quitting smoking, and require monitoring.
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EVIDENCE
See Part 1 for nicotine replacement therapy (NRT).
- Antidepressants: Cochrane review of bupropion 65 and nortriptyline 10 randomized controlled trials (RCTs).1
- Risk Ratio (RR) for cessation over placebo,
- Bupropion (at 6-12 months): 1.62 (1.49-1.76)
- Nortriptyline (at 6 months): 2.03 (1.48-2.78)
- Serious adverse events:
- Bupropion: Seizure (about 1/1000) and suicidal thoughts/behavior (association unclear) are rare.
- SSRI (6 RCTs) and venlafaxine (1 RCTs): not effective.
- Risk Ratio (RR) for cessation over placebo,
- Varenicline:
- Cochrane review2 of 39 RCTs: RR for cessation at 6-12 months over placebo= 2.24 (2.06-2.43)
- RR over bupropion= 1.39 (1.25-1.54)
- RR over NRT = 1.25 (1.14-1.37)
- Serious Adverse Events: RR 1.25 (1.05-1.49)
- Neuropsychiatric safety: Early studies2,3 suggested possible increase in depression, irritability, and suicidal thoughts/attempts, however:
- Systematic review4 of 39 RCTs: No increase versus placebo
- RCT5 0f 8,144 (50% with psychiatric disorder): No difference versus placebo, NRT or bupropion
- Cohort6 of ~120,000 patients: No difference between varenicline, bupropion or NRT.
- Cardiovascular events: No increase (see updated Tools for Practice #71).
- Cochrane review2 of 39 RCTs: RR for cessation at 6-12 months over placebo= 2.24 (2.06-2.43)
- Assuming 10% placebo cessation rates (mean across studies), number needed to treat: Varenicline 8, Nortriptyline 10 and Buproprion 10.
- Risk of bias in varenicline evidence:
- Superiority of varenicline > buproprion is at risk of funding bias
- Previously noted publication bias: In 2011, 75% of varenicline trials were unpublished.7
- Health Canada recommends “thorough consideration” of NRT before varenicline or bupropion.8
- Dosing:
- Lower doses are effective:
- Bupropion 150 mg is equivalent to 300 mg1,9
- Varenicline 0.5 mg BID may be slightly less effective than 1 mg BID (with fewer adverse events)2,10
- Nortriptyline: Can start at 25 mg qhs and increase by 25 mg every 3-4 days, if needed, to a maximum of 75-100 mg. Encouraged quit date 10 days in (or so) and continue for 10-12 weeks.
- Lower doses are effective:
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