What is the recommended dose of Wellbutrin (bupropion) for smoking cessation?

Wellbutrin Dosing for Smoking Cessation

The recommended dose of Wellbutrin (bupropion SR) for smoking cessation is 150 mg twice daily (300 mg total per day), starting 1-2 weeks before the target quit date and continuing for 7-12 weeks. 1

Standard Dosing Protocol

Initiation Schedule:

• Start with 150 mg once daily for the first 3 days 1
• Increase to 150 mg twice daily (300 mg total) on day 4 if tolerated 1
• Begin treatment 1-2 weeks before the planned quit date to establish therapeutic drug levels 1
• The maximum daily dose should not exceed 300 mg for smoking cessation to minimize seizure risk 1

Treatment Duration:

• Continue therapy for 7-12 weeks 1
• Assess efficacy at the end of this period 1
• If no significant progress toward abstinence is achieved by week 7-12, treatment should be reassessed 1

Timing of Administration

To minimize insomnia risk:

• Take the first dose in the morning 2
• Take the second dose before 3 PM 2, 3
• This timing is critical as bupropion has activating properties that can disrupt sleep if taken late in the day 2

Special Population Dose Adjustments

Hepatic Impairment:

• For moderate to severe hepatic impairment, reduce the total daily dose to 150 mg daily (one tablet only) 1, 2

Renal Impairment:

• For moderate to severe renal impairment (GFR <90 mL/min), reduce the total daily dose by half 1, 2
• Bupropion and its metabolites are cleared renally and may accumulate, requiring close monitoring 2

Older Adults:

• Start with 37.5 mg once daily in the morning 3
• Increase by 37.5 mg every 3 days as tolerated 3
• Maximum dose remains 150 mg twice daily (300 mg total) 3

Absolute Contraindications

Do not prescribe bupropion if the patient has:

• Seizure disorders (risk approximately 1 in 1,000) 4, 1
• Current or history of bulimia or anorexia nervosa (increased seizure risk) 2, 3
• Current use of MAOIs or within 14 days of discontinuing MAOIs 1, 2
• Hypersensitivity to bupropion (risk of allergic reaction 1 in 1,000 to 1 in 10,000) 4, 1
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs 2

Important Monitoring Requirements

Neuropsychiatric Monitoring:

• Monitor for hostility, agitation, depressed mood, and suicidal thoughts, particularly in patients under 24 years 1, 3
• Obtain psychiatric history and assess suicide risk before prescribing 1

Cardiovascular Monitoring:

• Monitor blood pressure at baseline and during treatment 1, 3
• Bupropion should be avoided in patients with uncontrolled hypertension 1, 2
• However, bupropion can be used safely in patients with established cardiovascular disease, including peripheral artery disease 1

Efficacy Evidence

Clinical Outcomes:

• Bupropion improves 12-month sustained abstinence rates from approximately 11% with placebo to 19% with bupropion 1
• This represents a 64% increase in long-term quit rates compared to placebo 1
• The efficacy appears independent of its antidepressant effect 4, 1
• One landmark trial showed 30.3% abstinence at 12 months with bupropion versus 15.6% with placebo 5

Combination Therapy:

• Combining bupropion with nicotine replacement therapy (NRT) may provide additional benefit, with one study showing 35.5% abstinence versus 30.3% with bupropion alone, though this difference was not statistically significant 5
• Bupropion and NRT have equivalent efficacy when used separately 1

Behavioral Support Integration

Critical for Success:

• Published trials demonstrating efficacy included behavioral support with medium to heavy smokers (≥15 cigarettes per day) 4, 1
• Combining bupropion with behavioral counseling can increase 6-month cessation rates from 6.8% to 21.3% compared to verbal advice alone 1
• Comprehensive programs with individualized counseling plus pharmacotherapy provide optimal outcomes 1

Common Side Effects and Management

Most Frequent Adverse Events:

• Insomnia (most common—administer second dose before 3 PM) 5, 6
• Dry mouth 5, 6
• Headache 5, 6
• Nausea 6
• These are generally transient and often resolve without intervention 6

Discontinuation Rates:

• In clinical trials, 6-12% of patients discontinued due to adverse events 6
• The most common reason for stopping was insomnia, which can be managed by dose timing or temporary dose reduction 6

Clinical Pearls

Ideal Candidates:

• Patients with comorbid depression who want to quit smoking (addresses both conditions simultaneously) 1, 2
• Patients concerned about weight gain (bupropion combined with naltrexone can mitigate smoking cessation-associated weight gain) 2
• One study showed weight gain at 7 weeks was 1.7 kg with bupropion versus 2.1 kg with placebo 5

Cost-Effectiveness:

• The estimated cost per life-year saved from bupropion use is approximately £1,000 or $1,500 7