Bupropion is a monocyclic antidepressant, thought to inhibit the reuptake of both dopamine and norepinephrine. It may exert multiple mechanisms, producing craving relief from dopaminergic activity, and antagonism of nicotinic acetylcholine receptors. The U.S. Public Health Service (PHS) guidelines and other analyses show that bupropion doubles long-term abstinence compared with placebo (Eisenberg et al., 2008; Fiore et al., 2008). Dosing begins 1 week before the quit date: 150 mg for 3 days, then 150 mg twice daily for the remainder of the week until quit day, and long-term maintenance at that dose. Bupropion may also be effective in relapse prevention, although a recent Cochrane review questions that conclusion (Hajek et al., 2008). Bupropion carries a small risk of seizures, as with other antidepressants, and is contraindicated in patients with a significant history of head trauma, eating disorders, or seizure disorders. Bupropion is effective in delaying weight gain associated with smoking cessation. The FDA has issued a black-box warning for both bupropion and varenicline, highlighting the risk of serious mental health events, including changes in behavior, depressed mood, hostility, agitation, suicidal thoughts, and attempted suicide.

Combination Therapy

Just as long-acting and short-acting NRT can be combined to augment cessation success, bupropion can be used with the patch or other forms of NRT. Combination therapy appears to be a promising approach. A 9-week study combining bupropion SR with transdermal nicotine found much greater efficacy than with either medication alone (Jorenby et al., 1999), and subsequent review in the PHS guidelines confirms the utility of combination therapy (Fiore et al., 2008). One might think of bupropion or the patch as the "controller" medication and the short-acting NRT as the "rescue" drug, much as dual therapy is used in asthma control. A recent trial of "triple therapy" using the patch, bupropion, and the nicotine vapor inhaler for up to 6 months showed a 2.57 odds ratio for abstinence compared with patch alone (Steinberg et al., 2009).

Clinicians at the Mayo Clinic Nicotine Dependence Center have routinely used combination therapy and base initial NRT patch dosing on venous cotinine levels. If that is not available, the intensity of smoking or spit tobacco use can be a useful guide (Table 50-1) (Dale et al., 2000).

Table 50-1 Recommended Dosages for Nicotine Replacement Therapy

Cigarettes (per day)

Nicotine Patch Dose (mg/day)

Less than 10






More than 40


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