What is the recommended dosage and duration of a short course of Wellbutrin (bupropion) for a patient with depression or smoking cessation, considering potential side effects and past medical history?

Wellbutrin Short Course: Dosing and Duration Guidelines

For smoking cessation, initiate bupropion SR 150 mg once daily for 3 days, then increase to 150 mg twice daily (300 mg total) starting 1-2 weeks before the target quit date, and continue for 7-12 weeks after quitting. 1, 2

Smoking Cessation Protocol

Pre-Quit Initiation Strategy

• Begin bupropion 1-2 weeks before the target quit date to establish therapeutic drug levels before the cessation attempt 1, 2
• This lead time is critical—do not start treatment on the quit date itself 2

Standard Titration Schedule

• Days 1-3: 150 mg orally once daily 1, 2
• Day 4 through end of treatment: 150 mg orally twice daily (300 mg total) if tolerated 1, 2
• Maximum dose: 300 mg per day for smoking cessation—never exceed this to maintain seizure risk at 0.1% 1, 2, 3

Treatment Duration

• Continue for 7-12 weeks after the quit date 1, 2
• Assess efficacy formally after this 7-12 week period 1, 2
• Therapy may be extended to promote continued cessation (up to 6 months-1 year) while attempting to avoid longer periods if possible 1

Combination Therapy Considerations

• Bupropion plus nicotine replacement therapy (NRT) shows the highest abstinence rates (35.5% at 12 months vs 30.3% with bupropion alone), though the difference is not statistically significant 2
• When combining with NRT, monitor blood pressure more closely as 6.1% of patients develop treatment-emergent hypertension versus 2.5% with bupropion alone 3
• Begin nicotine patches on the actual quit date, not when starting bupropion 2

Depression Treatment Protocol

Initial Dosing for Major Depressive Disorder

• Bupropion SR: 150 mg once daily for 3 days, then increase to 150 mg twice daily (300 mg total) 2
• Bupropion XL: 150 mg once daily initially, with maintenance dose of 150-300 mg once daily 2
• Maximum doses: 400 mg/day for SR formulation; 450 mg/day for XL formulation 2, 3

Treatment Duration Assessment

• Continue for at least 6-8 weeks at therapeutic dose before determining adequacy of response 2
• Monitor patient status, therapeutic response, and adverse effects within 1-2 weeks of initiation 2
• Treatment for a first episode of major depression should last at least 4 months 4
• Do not discontinue prematurely before adequate treatment duration unless significant adverse effects occur 4

Efficacy Timeline

• Energy levels may improve within the first few weeks, faster than with other antidepressants 2
• Full antidepressant response requires 6-8 weeks at adequate doses 2
• Response rates are approximately 42-49% for remission, similar to SSRIs and SNRIs 2

Critical Safety Screening Before Prescribing

Absolute Contraindications

• Seizure disorders or any condition predisposing to seizures (stroke, brain metastases, head trauma, brain tumor) 1, 2, 3
• Current or recent MAOI use (within 14 days of discontinuation) due to increased risk of hypertensive reactions 1, 2
• Eating disorders (bulimia nervosa or anorexia nervosa) due to increased seizure risk 1, 2
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs 1, 2
• Uncontrolled hypertension 2, 3
• Chronic opioid therapy (for naltrexone-bupropion combination products only) 2

Special Population Dose Adjustments

• Moderate to severe hepatic impairment: Maximum 150 mg daily (one tablet) 2
• Moderate to severe renal impairment (GFR <90 mL/min): Reduce total daily dose by 50% 2
• Older adults: Start with 37.5 mg every morning, increase by 37.5 mg every 3 days as tolerated, maximum 150 mg twice daily 2

Monitoring Requirements

Blood Pressure and Cardiovascular Monitoring

• Assess blood pressure before initiating treatment and monitor periodically during therapy, especially in the first 12 weeks 2, 3
• Mean systolic blood pressure increase of 1.3 mmHg in clinical trials 3
• When combined with NRT, 6.1% develop treatment-emergent hypertension versus 2.5% with bupropion alone 3

Neuropsychiatric Monitoring

• Monitor for development or worsening of depression, suicidal ideation/behavior, hostility, agitation, and behavioral changes, especially in patients under 24 years 1, 2
• Risk for suicide attempts is greatest during the first 1-2 months of treatment 2
• Discontinue if serious neuropsychiatric issues develop 1
• Recent multicenter RCT showed neuropsychiatric adverse events with bupropion were not significantly increased relative to placebo in patients with or without psychiatric disorders 1

Seizure Risk Management

• Seizure risk is approximately 0.1% (1 in 1,000) at 300 mg/day 2, 5
• Risk increases with doses above 300 mg/day for smoking cessation or 450 mg/day for depression 2, 3
• Gradual titration is necessary to minimize seizure risk 2

Common Side Effects and Management

Most Frequent Adverse Events

• Insomnia and dry mouth are the most common side effects, occurring significantly more frequently than placebo 5, 6
• Insomnia, headache, dry mouth, nausea, and anxiety are most commonly reported 5
• Insomnia and anxiety are also recognized symptoms of nicotine withdrawal 5
• These side effects are generally transient and often resolve quickly without intervention 5

Side Effect Management

• Administer second dose before 3 PM to minimize insomnia risk 2
• If side effects occur, consider dose reduction rather than discontinuation 5
• Discontinuation rates due to adverse events are low (6-12%) in clinical trials 5
• Weight loss of 0.5-1.0 kg is common, which may be beneficial for some patients 7

Clinical Advantages for Specific Populations

Dual Benefit Scenarios

• Patients with depression who also want to quit smoking benefit from addressing both conditions simultaneously 1, 2
• Patients with depression characterized by low energy, apathy, or hypersomnia benefit from bupropion's activating properties 2
• Patients concerned about sexual dysfunction (significantly lower rates than SSRIs) or weight gain 2

Treatment-Resistant Depression

• When bupropion monotherapy fails after 6-8 weeks, augment with an SSRI or SNRI rather than switching 2
• Augmenting SSRIs with bupropion decreases depression severity more effectively than buspirone augmentation 2
• Bupropion augmentation shows significantly lower discontinuation rates due to adverse events (12.5% vs 20.6%, P<0.001) compared to buspirone 2

Discontinuation Strategy

Tapering Approach

• Gradual dose reduction is recommended to minimize potential withdrawal symptoms 2, 4
• While explicit tapering protocols are not provided in guidelines, a practical approach based on hepatic impairment dosing suggests reducing to 150 mg daily, then 150 mg every other day before stopping 4
• Monitor patient status within 1-2 weeks of any dosing change 4

Critical Timing Considerations

• Do not discontinue before adequate treatment duration (at least 4 months for first episode of depression) unless significant adverse effects occur 4
• Risk for suicide attempts may persist during discontinuation, particularly in patients under 24 years 4

Important Clinical Pearls

• Formulation switching requires close monitoring due to historical bioequivalence issues between brand and generic or SR and XL formulations 2, 4
• No significant pharmacokinetic interactions preclude combining bupropion with SSRIs, though both lower seizure threshold 2
• Bupropion is present in breast milk at low levels; two case reports of seizures in breastfed infants warrant caution 2
• Limited data suggest no major congenital malformations with bupropion use during pregnancy, though small increases in specific cardiovascular defects have been reported 2