Is Wellbutrin (bupropion) effective for smoking cessation in patients with a history of depression or anxiety?

Wellbutrin (Bupropion) for Smoking Cessation in Patients with Depression or Anxiety

Bupropion is highly effective for smoking cessation in patients with a history of depression or anxiety, achieving 23% sustained abstinence at one year compared to 12% with placebo, and may be particularly beneficial in this population. 1

Evidence for Efficacy in Depression and Anxiety

Bupropion demonstrates superior efficacy for smoking cessation regardless of psychiatric history. The EAGLES trial (n=8,144) showed bupropion achieved significantly better abstinence rates than placebo (OR 2.07; 95% CI 1.75-2.45), with efficacy similar to nicotine patch though less than varenicline. 1 A 2014 Cochrane review of 44 trials revealed a relative risk of 1.62 (95% CI 1.49-1.76) for smoking cessation with bupropion. 1

Patients with depression history respond particularly well to bupropion. A large UK trial (n=1,071) noted a trend toward improved efficacy in patients with a history of depression (χ2=2.86; P=0.091). 1 A separate study of 615 smokers found bupropion efficacy was independent of former history of major depression or alcoholism, with significant dose-response effects maintained across all psychiatric subgroups. 2

For anxiety specifically, patients with higher baseline anxiety scores showed better long-term outcomes. In a 6-month follow-up study, patients who remained abstinent had significantly higher anxiety scores at baseline than those who relapsed (p=0.017 at 6 months). 3 Depression levels influenced outcome only during the first month of treatment. 3

Dosing Protocol

Start bupropion SR 150 mg once daily for 3 days, then increase to 150 mg twice daily (300 mg total), beginning 1-2 weeks before the target quit date. 1, 4 This lead time allows therapeutic drug levels to establish before cessation attempts. 4

• Administer the first dose in the morning and the second dose before 3 PM to minimize insomnia risk. 4
• Continue treatment for 7-12 weeks after the quit date, with formal efficacy assessment after this period. 1, 4
• The maximum dose for smoking cessation is 300 mg per day—do not exceed this to maintain seizure risk at 0.1%. 1, 4

Combination with Nicotine Replacement Therapy

Adding NRT to bupropion shows the highest abstinence rates, though the difference is not statistically significant. A double-blind RCT demonstrated 12-month abstinence rates of 35.5% with bupropion plus NRT compared to 30.3% with bupropion alone. 1 A 2014 meta-analysis of 12 trials showed a nonsignificant trend favoring the combination. 1

For patients with comorbid depression and nicotine dependence, this combination addresses both conditions simultaneously. 4

Safety Considerations in Psychiatric Populations

Neuropsychiatric adverse events are rarely associated with bupropion, even in patients with mental illness. The EAGLES trial found no significant increase in neuropsychiatric events with bupropion relative to nicotine patch or placebo. 1 Recent systematic reviews confirm serious neuropsychiatric adverse events were rare, including in studies of patients with mental illness. 1

Bupropion carries a 0.1% seizure risk at recommended doses. 1, 4 Absolute contraindications include:

• Current seizure disorder or history of seizures 1, 4
• Eating disorders (bulimia or anorexia nervosa) 4
• Abrupt discontinuation of alcohol, benzodiazepines, or antiepileptic drugs 1, 5
• Current or recent MAOI use (within 14 days) 4
• Uncontrolled hypertension 4

Monitor blood pressure and heart rate periodically, especially during the first 12 weeks, as bupropion can elevate both parameters. 4

Depression Monitoring During Treatment

Increases in depressive symptoms during initial abstinence predict return to smoking. Among patients continuously abstinent for two weeks following the quit date, increased Beck Depression Inventory scores were associated with relapse at end of treatment. 2 However, no evidence of emergent depression occurred in patients maintained on SSRIs who added bupropion for smoking cessation. 6

For patients on SSRI maintenance therapy, adding bupropion SR 300 mg/day for smoking cessation is safe and modestly effective (32% abstinent at 9 weeks). 6 Additional benefits include minimal weight gain (0.5 lb over 9 weeks) and spontaneous improvement in SSRI-associated sexual dysfunction (16% of patients). 6

Common Side Effects

Side effects are more common with bupropion than NRT alone but are generally manageable. The most frequent include disturbed sleep, dry mouth, headaches, and nausea. 1 Five serious adverse events occurred in 1,071 patients in the UK trial, including allergic reactions (n=3), neuropsychiatric symptoms (n=1), and chest pain (n=1). 1

Weight gain is minimal with bupropion. Among continuously abstinent patients, mean weight gain was inversely associated with dose: 2.9 kg with placebo, 2.3 kg with 150 mg, and 1.5 kg with 300 mg. 7

Clinical Advantages in Psychiatric Populations

Bupropion addresses both smoking cessation and depressive symptoms simultaneously. This dual benefit makes it particularly valuable for patients with depression who want to quit smoking. 1, 4 Longer duration of bupropion treatment may help prevent relapse in those who successfully quit. 1

For highly nicotine-dependent smokers with depression, bupropion decreases depressive symptoms during active treatment. However, these patients may experience rebound depressive symptoms when bupropion is discontinued, suggesting consideration for extended treatment duration. 8

Treatment Discontinuation

Patients should discontinue bupropion immediately if they experience a seizure, severe allergic reaction, or significant neuropsychiatric symptoms including suicidal ideation, severe mood changes, or psychotic symptoms. 5 Instruct patients and families to monitor for emergence of anxiety, agitation, panic attacks, hostility, aggressiveness, unusual behavior changes, or worsening depression, especially during early treatment. 5