Does bupropion (Wellbutrin) XL help with smoking cessation?

Bupropion XL for Smoking Cessation

Yes, bupropion XL is highly effective for smoking cessation and should be offered as a first-line pharmacological aid, increasing long-term quit rates by approximately 64% compared to placebo. 1, 2

Evidence for Efficacy

Bupropion significantly improves smoking cessation outcomes across multiple high-quality studies:

• Quit rates increase from approximately 11% with placebo to 19% with bupropion at one year, representing a substantial clinical benefit 1
• A Cochrane systematic review of 45 studies involving 17,866 participants found high-certainty evidence that bupropion increases long-term cessation rates (RR 1.64,95% CI 1.52 to 1.77) 2
• The mechanism appears independent of antidepressant effects, working primarily through dopamine and norepinephrine reuptake inhibition 1, 3

Dosing and Administration

Standard dosing for bupropion XL is 300 mg once daily in the morning, while bupropion SR is dosed as 150 mg twice daily (total 300 mg/day). 4, 5

The titration schedule should be:

• Days 1-3: 150 mg once daily 4, 5
• Day 4 onward: 150 mg twice daily (SR formulation) or 300 mg once daily (XL formulation) 4, 5
• Begin treatment 1-2 weeks before the target quit date to establish therapeutic drug levels 1, 4, 5
• Continue for 7-12 weeks, with efficacy assessed at the end of this period 1, 4, 5

Comparative Effectiveness

Bupropion's efficacy relative to other cessation aids:

• Varenicline is superior to bupropion, with quit rates of 28% versus 19% respectively 1, 2
• Bupropion and NRT have equivalent efficacy (RR 0.99,95% CI 0.91 to 1.09) 2
• Nortriptyline has similar efficacy to bupropion but is considered second-line due to side effects 1, 2

Combination Therapy

Evidence for combining bupropion with other agents is mixed:

• Combining bupropion with NRT may provide additional benefit over NRT alone, though evidence is insufficient to confirm superiority (RR 1.19,95% CI 0.94 to 1.51) 1, 2
• Combining bupropion with varenicline does not clearly improve outcomes over varenicline alone (RR 1.21,95% CI 0.95 to 1.55) 2

Safety Profile and Monitoring

Bupropion is generally safe but requires specific monitoring and has important contraindications:

Seizure Risk

• Risk is approximately 1 in 1,000, similar to other antidepressants 1, 4
• Maximum dose must not exceed 300 mg/day for smoking cessation to minimize seizure risk 4, 5
• Absolutely contraindicated in patients with seizure disorders, eating disorders (bulimia/anorexia), or abrupt discontinuation of alcohol/benzodiazepines 4, 5

Neuropsychiatric Effects

• Monitor for hostility, agitation, depressed mood, and suicidal thoughts, particularly in patients under 24 years 1, 4
• Obtain psychiatric history and assess suicide risk before prescribing 1
• Consider postponing bupropion and using NRT alone if current psychiatric distress is present 1

Common Side Effects

• Insomnia and dry mouth are most common, affecting up to 50% of patients 3, 2
• Patients are 37% more likely to discontinue treatment due to adverse events compared to placebo (RR 1.37,95% CI 1.21 to 1.56) 2
• Psychiatric adverse events occur 25% more frequently than with placebo (RR 1.25,95% CI 1.15 to 1.37) 2

Drug Interactions

• Contraindicated with MAOIs or within 14 days of MAOI discontinuation 4, 5
• Inhibits CYP2D6, potentially raising levels of antidepressants, antiarrhythmics, and antipsychotics 3, 6
• Avoid in patients taking tamoxifen due to metabolic interference 5

Special Populations

Hepatic Impairment

• Maximum dose is 150 mg daily (one tablet) for moderate to severe hepatic impairment 4, 5

Renal Impairment

• Reduce total daily dose by half for moderate to severe renal impairment (GFR <90 mL/min) 4, 5

Cardiovascular Disease

• Monitor blood pressure; avoid in uncontrolled hypertension 4, 5
• Can be used safely in patients with established cardiovascular disease, including peripheral artery disease 1

Depression

• Bupropion may be particularly beneficial for patients with comorbid depression who want to quit smoking, addressing both conditions simultaneously 1, 4, 5

Behavioral Support Integration

Bupropion should be combined with behavioral counseling for optimal outcomes:

• Published trials demonstrating efficacy included behavioral support with medium to heavy smokers (≥15 cigarettes/day) 1, 4
• Comprehensive programs with individualized counseling plus pharmacotherapy increase 6-month cessation rates from 6.8% to 21.3% compared to verbal advice alone 1
• At minimum, provide tailored self-help materials and arrange follow-up 1

Clinical Decision Algorithm

Use bupropion XL when:

1. Patient smokes ≥15 cigarettes/day and desires pharmacological assistance 1
2. No contraindications (seizure disorder, eating disorder, MAOI use, uncontrolled hypertension) 4, 5
3. Patient prefers once-daily dosing or has comorbid depression 4, 5
4. Varenicline is declined, contraindicated, or previously unsuccessful 2

Choose varenicline over bupropion when:

• Maximum efficacy is the priority and no psychiatric contraindications exist 1, 2

Choose NRT over bupropion when:

• Patient has psychiatric history raising concerns about neuropsychiatric effects 1
• Drug interactions are a concern 3, 6
• Patient is pregnant (bupropion lacks safety data in pregnancy) 1