What is the starting dose of Wellbutrin (bupropion) for a typical adult patient with Major Depressive Disorder (MDD)?

Starting Dose of Wellbutrin (Bupropion) for Major Depressive Disorder

For a typical adult with MDD, start Wellbutrin XL at 150 mg once daily in the morning, then increase to the target dose of 300 mg once daily after 4 days. 1

Standard Dosing Protocol

The FDA-approved dosing for bupropion XL (extended-release) follows a straightforward titration schedule 1:

• Days 1-4: 150 mg once daily in the morning
• Day 5 onward: Increase to 300 mg once daily in the morning (target therapeutic dose)

This represents the most direct path to therapeutic dosing for most patients without hepatic or renal impairment 1.

Alternative Formulation: Bupropion SR

If using the sustained-release (SR) formulation instead of XL, the American Family Physician recommends 2:

• Days 1-3: 150 mg once daily in the morning
• Day 4 onward: 150 mg twice daily (300 mg total daily dose)
• Critical timing: The second dose must be taken before 3 PM to minimize insomnia risk 2

Both formulations achieve the same target dose of 300 mg/day but differ in administration frequency 2.

Modified Dosing for Special Populations

Older Adults (≥60 years)

Start lower and go slower in elderly patients due to increased risk of adverse reactions 2:

• Initial dose: 37.5 mg once daily in the morning
• Titration: Increase by 37.5 mg every 3 days as tolerated
• Target dose: 150 mg twice daily (maximum 300 mg/day)
• Timing: Second dose before 3 PM 2

This conservative approach reduces the risk of agitation, insomnia, and other adverse effects in older adults 2.

Patients on Multiple Psychotropic Medications

Use the same conservative titration as for older adults 2:

• Start at 37.5 mg once daily in the morning
• Increase by 37.5 mg every 3 days
• Monitor closely for increased agitation (bupropion is activating) 2
• Target dose of 150 mg twice daily (maximum 300 mg/day) 2

Hepatic Impairment

Moderate to severe hepatic impairment (Child-Pugh 7-15): Maximum dose is 150 mg every other day 1

Mild hepatic impairment (Child-Pugh 5-6): Consider reducing dose and/or frequency 1

Renal Impairment

GFR <90 mL/min: Reduce total daily dose by 50% 2

Consider reducing dose and/or frequency in any degree of renal impairment 1

Critical Safety Considerations Before Initiating

Absolute Contraindications

Do not prescribe bupropion if the patient has 2, 1:

• Seizure disorder or any condition predisposing to seizures (brain tumor, head trauma, stroke)
• Current or recent MAOI use (must wait 14 days after stopping MAOI)
• Eating disorders (bulimia or anorexia nervosa) - significantly increases seizure risk
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs - precipitates withdrawal seizures
• Uncontrolled hypertension - bupropion elevates blood pressure 2

Pre-Treatment Screening

Before writing the first prescription 2:

• Blood pressure and heart rate: Bupropion can elevate both parameters
• Seizure history: Any personal or family history of seizures
• Substance use: Current alcohol or benzodiazepine use (abrupt discontinuation contraindicated)
• Eating disorder history: Even remote history increases seizure risk
• Medication review: Check for MAOIs, tamoxifen (contraindicated), or other seizure threshold-lowering drugs
• Suicidal ideation assessment: Especially critical in patients <24 years (black box warning) 2

Monitoring Timeline

First 1-2 Weeks

Monitor for 2:

• Worsening depression or suicidal ideation (highest risk period in patients <24 years)
• Agitation or restlessness (bupropion is activating)
• Insomnia (dose timing may need adjustment)
• Blood pressure elevation

Week 6-8

Assess for adequate therapeutic response 2:

• If no response after 6-8 weeks at 300 mg/day, consider treatment modification
• Do not discontinue prematurely before this timeframe unless significant adverse effects occur 2
• Some patients may experience improved energy within the first few weeks, but full antidepressant effect requires 6-8 weeks 2

Clinical Advantages of Bupropion

Bupropion may be particularly beneficial for patients with 2:

• Low energy, apathy, or hypersomnia (activating properties)
• Concerns about sexual dysfunction (significantly lower rates than SSRIs)
• Concerns about weight gain (associated with weight loss or minimal weight gain)
• Comorbid smoking cessation goals (FDA-approved for both indications)

Common Pitfalls to Avoid

Do not exceed 450 mg/day total - seizure risk increases significantly above this dose 2, 1

Do not give the second dose of SR formulation after 3 PM - causes insomnia 2

Do not switch between brand and generic formulations without close monitoring - historical bioequivalence issues may lead to loss of efficacy 2

Do not combine with naltrexone-bupropion products if patient is on opioids - naltrexone will precipitate withdrawal 2

Do not start in patients actively using alcohol or benzodiazepines who may abruptly discontinue - withdrawal seizures are contraindicated 2