What is the recommended dose of Wellbutrin (bupropion)?

Wellbutrin (Bupropion) Dosing

For major depressive disorder, start bupropion SR at 150 mg once daily for 3 days, then increase to 150 mg twice daily (300 mg total daily) if tolerated, with a maximum dose of 400 mg/day for SR formulation or 450 mg/day for XL formulation. 1, 2

Standard Dosing by Formulation

Bupropion SR (Sustained Release)

• Initial dose: 150 mg once daily in the morning for days 1-3 1, 2
• Maintenance dose: 150 mg twice daily (300 mg total) starting day 4 1, 2
• Maximum dose: 400 mg per day 2
• Timing: Second dose must be taken before 3 PM to minimize insomnia risk 2, 3

Bupropion XL (Extended Release)

• Initial dose: 150 mg once daily in the morning for 1 week 4
• Maintenance dose: 300 mg once daily 2, 4
• Maximum dose: 450 mg per day 2, 5
• Timing: Take in the morning only 2

The FDA label confirms that 78% of patients in efficacy trials were treated with 300-450 mg per day, with the 450 mg dose demonstrating superior efficacy in one pivotal trial 4. All three formulations (IR, SR, XL) are bioequivalent at steady state, meaning systemic exposure to bupropion and its metabolites are similar 4, 6, 7.

Indication-Specific Dosing

Smoking Cessation

• Dose: 150 mg once daily for days 1-3, then 150 mg twice daily (300 mg total) 1, 2
• Maximum: 300 mg per day for smoking cessation 1, 2
• Timing: Begin 1-2 weeks before target quit date 1, 2
• Duration: 7-12 weeks, with possible extension to 6 months-1 year 1, 2

Seasonal Affective Disorder

• Dose: 150 mg once daily for 1 week, then 300 mg once daily 4
• Timing: Initiate in autumn (September-November) before symptom onset 4
• Duration: Approximately 4-6 months, discontinuing with 2-week taper in spring 4

Special Population Adjustments

Older Adults (≥55 years)

• Initial dose: 37.5 mg once daily in the morning 2, 3
• Titration: Increase by 37.5 mg every 3 days as tolerated 2, 3
• Maximum dose: 150 mg twice daily (300 mg total) 3
• The American Academy of Family Physicians recommends approximately 50% of standard adult starting doses for older adults due to increased risk of adverse reactions 1, 2

Hepatic Impairment

• Moderate to severe impairment: Maximum 150 mg daily (one tablet) 2
• Dose reduction required in both formulations 1, 2

Renal Impairment

• GFR <90 mL/min: Reduce total daily dose by half 2, 3
• Bupropion and metabolites accumulate with renal dysfunction, requiring close monitoring 2, 3

Critical Safety Considerations

Absolute Contraindications

• Seizure disorders or conditions that lower seizure threshold (stroke, brain metastases, eating disorders) 1, 2, 3
• Concurrent MAOI use or within 14 days of discontinuing MAOIs 1, 2
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs 2
• Uncontrolled hypertension requires close blood pressure monitoring 2, 3

The maximum dose must not exceed 450 mg per day to minimize seizure risk, which occurs in approximately 0.4% of patients at doses up to 450 mg/day 2, 5. The NCCN guidelines note that bupropion is contraindicated in patients with brain metastases due to seizure risk 1.

Drug Interactions

• Tamoxifen: Concurrent use may reduce tamoxifen efficacy 2, 3
• CYP2D6 substrates: Bupropion inhibits CYP2D6 and may reduce clearance of these agents 8
• CYP2B6 inhibitors: Use caution as bupropion is metabolized by CYP2B6 3, 8

Monitoring Requirements

• Neuropsychiatric symptoms: Monitor for depression worsening, suicidal ideation (especially in patients <24 years), agitation, anxiety, and mood changes 1, 2, 3
• Blood pressure: Check at baseline and during titration, as bupropion can cause elevations 3
• Efficacy assessment: Allow 6-8 weeks at adequate dose before determining treatment response 2

A recent multicenter RCT found that neuropsychiatric adverse events with bupropion were not significantly increased relative to nicotine patches or placebo in patients with or without psychiatric disorders 1.

Clinical Advantages and Considerations

Bupropion offers distinct advantages over SSRIs: lower rates of sexual dysfunction, less somnolence, and potential for weight loss rather than weight gain 1, 2, 6, 7. Patients lost a mean of 0.5-1.0 kg with bupropion SR compared to 0.2 kg with placebo 9.

The medication may be particularly beneficial for patients with depression characterized by low energy, apathy, or hypersomnia due to its activating properties 2. It is the only antidepressant with no appreciable serotonin activity, working instead through norepinephrine and dopamine reuptake inhibition 5, 6, 7.

Common side effects include insomnia (managed by proper timing of doses), agitation, dry mouth, nausea, headache, and tremor 1, 2, 3, 5. Insomnia is the most common side effect and can be minimized by ensuring the second SR dose is before 3 PM or taking XL formulation in the morning only 2, 3.