What is the optimal dose of bupropion (Wellbutrin) for a patient seeking to quit smoking?

Optimal Bupropion Dose for Smoking Cessation

The optimal dose of bupropion for smoking cessation is 150 mg twice daily (300 mg total daily) of the sustained-release (SR) formulation, started 1-2 weeks before the target quit date and continued for 7-12 weeks. 1, 2

Standard Dosing Protocol

Titration Schedule:

• Start with 150 mg once daily for the first 3 days 1, 2
• Increase to 150 mg twice daily (300 mg total) from day 4 onward 1, 2
• Begin treatment 1-2 weeks before the target quit date to establish therapeutic drug levels 1, 2
• Continue for 7-12 weeks total, with efficacy assessed at the end of this period 1, 2

Critical Maximum Dose:

• Never exceed 300 mg per day for smoking cessation to maintain seizure risk at 0.1% 1, 2
• This maximum is lower than the 450 mg daily limit used for depression treatment 1

Efficacy Data

The evidence strongly supports this dosing regimen:

• Bupropion 300 mg/day increases 12-month quit rates from approximately 11-16% with placebo to 19-30% 2, 3
• This represents a 9-10 percentage point improvement in sustained abstinence rates 1, 4
• The efficacy appears independent of bupropion's antidepressant effects 2
• Combination with behavioral support is essential, as published efficacy data primarily comes from studies including behavioral interventions 1, 2

Timing Considerations to Minimize Side Effects

To prevent insomnia (the most common side effect):

• Take the first dose in the morning 1, 5
• Take the second dose before 3 PM 1, 5
• This timing leverages bupropion's activating properties while minimizing sleep disturbance 1

Dose Adjustments for Special Populations

Hepatic Impairment:

• Moderate to severe hepatic impairment: Maximum 150 mg daily (one tablet total) 1, 2

Renal Impairment:

• GFR <90 mL/min: Reduce total daily dose by half 1, 5, 2
• Close monitoring required as bupropion and metabolites accumulate with renal dysfunction 5

Older Adults (≥55 years):

• Start with 37.5 mg once daily in the morning 5
• Increase by 37.5 mg every 3 days as tolerated 5
• Maximum dose remains 150 mg twice daily (300 mg total) 5

Absolute Contraindications

Do not prescribe bupropion if the patient has:

• Any seizure disorder (seizure risk approximately 1 in 1,000) 1, 2, 4
• Current or recent MAOI use (within 14 days) 1, 2
• Eating disorders (bulimia or anorexia nervosa) due to increased seizure risk 1, 5
• Severe hepatic cirrhosis 2, 4
• Abrupt discontinuation of alcohol, benzodiazepines, or antiepileptic drugs 1
• Uncontrolled hypertension 1, 5, 2

Critical Monitoring Parameters

Before Starting:

• Screen for seizure risk factors 2, 4, 6
• Obtain psychiatric history and assess suicide risk, especially in patients <24 years 2
• Check baseline blood pressure 5, 2

During Treatment:

• Monitor blood pressure periodically, especially in first 12 weeks 5, 2
• Watch for neuropsychiatric symptoms: hostility, agitation, depressed mood, suicidal thoughts (particularly in patients <24 years) 1, 2
• Assess efficacy at 7-12 weeks; if no significant progress toward abstinence, reassess treatment 1, 2

Clinical Advantages

Bupropion may be particularly beneficial for:

• Patients with comorbid depression who want to quit smoking, addressing both conditions simultaneously 1, 2
• Patients concerned about weight gain, as bupropion limits post-cessation weight gain compared to placebo 1, 7, 3

Common Pitfalls to Avoid

• Do not exceed 300 mg/day for smoking cessation - higher doses increase seizure risk without improving efficacy 1, 2
• Do not start treatment on the quit date - begin 1-2 weeks early to establish therapeutic levels 1, 2
• Do not dose late in the day - second dose after 3 PM increases insomnia risk 1, 5
• Do not use in patients taking tamoxifen - bupropion may reduce tamoxifen efficacy 1, 5