Wellbutrin (Bupropion) for Smoking Cessation
Bupropion is an effective first-line pharmacological treatment for smoking cessation that significantly improves quit rates compared to placebo, with a standard dose of 150 mg twice daily (300 mg total) started 1-2 weeks before the target quit date and continued for 7-12 weeks. 1, 2, 3
Evidence for Efficacy
Bupropion increases long-term smoking cessation rates substantially. The ACC/AHA guidelines report that at 1 year, quit rates with bupropion range from 19.6% to 23.1% (depending on dose) compared to 12.4% with placebo 1. More recent evidence shows bupropion increases quit rates from approximately 11% with placebo to 19% at one year, representing a 64% relative improvement 3. When combined with intensive behavioral support, bupropion achieves abstinence rates approximately 9-10 percentage points above baseline 3.
The mechanism appears independent of bupropion's antidepressant effects—it works by inhibiting neuronal reuptake of dopamine and norepinephrine, counteracting the reinforcing effects of nicotine 1.
Dosing Protocol
Start bupropion SR 150 mg once daily for 3 days, then increase to 150 mg twice daily (300 mg total). 2, 3 This gradual titration minimizes seizure risk while achieving therapeutic levels 2.
Critical timing: Begin treatment 1-2 weeks before the target quit date to allow therapeutic drug levels to establish before the cessation attempt 2, 3. Do not start smoking cessation without this lead time 2.
Continue treatment for 7-12 weeks after the quit date, with formal efficacy assessment at the end of this period 1, 2, 3. If no significant progress toward abstinence occurs by weeks 7-12, reassess the treatment plan 3.
Maximum dose: Do not exceed 300 mg per day for smoking cessation to maintain seizure risk at approximately 0.1% (1 in 1,000) 2, 3.
Combination Therapy
Combining bupropion with nicotine replacement therapy (NRT) shows the highest abstinence rates. A double-blind RCT demonstrated 12-month abstinence rates of 35.5% with bupropion plus NRT compared to 30.3% with bupropion alone, though this difference was not statistically significant 2. Start nicotine patches on the actual quit date (not when starting bupropion) 2.
The combination is particularly beneficial for highly nicotine-dependent smokers and those who have failed monotherapy 4.
Absolute Contraindications
Do not prescribe bupropion if the patient has:
- Seizure disorder or any condition predisposing to seizures (severe head injury, arteriovenous malformation, CNS tumor, severe stroke) 1, 2, 3, 5
- Eating disorders (anorexia nervosa or bulimia) due to increased seizure risk 2, 3, 5
- Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs 2, 3, 5
- Current or recent MAOI use (within 14 days of discontinuing) 2, 3
- Uncontrolled hypertension 2, 3
Dose Adjustments for Special Populations
Hepatic impairment: For moderate to severe hepatic impairment, maximum dose is 150 mg daily (one tablet) 2, 3. For mild hepatic impairment, reduce dose and/or frequency 2.
Renal impairment: For moderate to severe renal impairment (GFR <90 mL/min), reduce total daily dose by 50% 2, 3. Avoid in end-stage renal disease 2.
Monitoring Requirements
Monitor for neuropsychiatric adverse effects, especially in patients under 24 years old 2, 3, 5. Watch for:
- Agitation, hostility, depressed mood
- Suicidal ideation or behavior
- Changes in behavior or thinking not typical for the patient
- Anxiety, panic attacks, insomnia, irritability 5
If these symptoms occur, stop bupropion immediately and contact healthcare provider 5. In many cases symptoms resolve after discontinuation, but some persist and require ongoing supportive care 5.
Monitor blood pressure and heart rate, particularly in the first 12 weeks, as bupropion can cause elevations 2, 3.
Common Side Effects
The most common side effects include insomnia, dry mouth, headache, and nausea 1, 2. Approximately 8% of patients stop treatment prematurely due to headache, insomnia, or dry mouth 1. These side effects are closely linked to nicotine withdrawal syndrome 6.
To minimize insomnia risk, administer the second dose before 3 PM 2.
Special Clinical Considerations
Bupropion may be particularly beneficial for patients with comorbid depression who want to quit smoking, addressing both conditions simultaneously 1, 2, 3. Evidence suggests a trend toward improved efficacy in patients with a history of depression 2.
Bupropion reduces post-cessation weight gain, which is common in smokers who quit 1, 7.
Behavioral support is essential. Published trials demonstrating efficacy included behavioral counseling with medium to heavy smokers (≥15 cigarettes per day) 1, 3. Combining bupropion with comprehensive behavioral programs can increase 6-month cessation rates from 6.8% to 21.3% compared to verbal advice alone 3.
Comparative Effectiveness
While bupropion is effective, varenicline demonstrates superior efficacy with quit rates of 28% versus 19% for bupropion 3. However, bupropion and NRT have equivalent efficacy 3.
One randomized trial found higher one-year sustained abstinence rates with bupropion than transdermal nicotine patch in the context of behavioral support, though further research is needed for firm conclusions 1.
Safety in Cardiovascular Disease
Bupropion can be used safely in patients with established cardiovascular disease, including those with peripheral artery disease 3. The ACC/AHA guidelines specifically note bupropion as an option for patients who need to quit smoking after acute myocardial infarction 1.