What is the recommended dosing regimen for bupropion (Wellbutrin)?

Bupropion (Wellbutrin) Dosing Regimen

The recommended dosing regimen for bupropion (Wellbutrin) in Major Depressive Disorder (MDD) is to start at 150 mg once daily in the morning for the first 4 days, then increase to the target dose of 300 mg once daily. 1

Formulations and Administration

• Bupropion is available in three oral formulations:

  • Immediate-release (IR): Administered three times daily
  • Sustained-release (SR): Administered twice daily
  • Extended/modified-release (XL/XR): Administered once daily

• Administration guidelines:

  • Take in the morning
  • Swallow tablets whole (do not crush, divide, or chew)
  • Can be taken with or without food
  • Increase dose gradually to minimize seizure risk 1

Dosing for Major Depressive Disorder (MDD)

1. Initial dose: 150 mg once daily in the morning
2. Titration: After 4 days, increase to 300 mg once daily
3. Maintenance: Continue at effective dose (typically 300 mg daily)
4. Maximum dose: 450 mg per day 2, 1

Dosing for Seasonal Affective Disorder (SAD)

1. Initial dose: 150 mg once daily
2. Titration: After 7 days, increase to 300 mg once daily
3. Treatment duration: Start in autumn before symptom onset, continue through winter, taper in early spring
4. Tapering: Decrease from 300 mg to 150 mg once daily before discontinuation 1

Dosage Adjustments for Special Populations

Hepatic Impairment

• Moderate to severe impairment (Child-Pugh score 7-15): Maximum 150 mg every other day
• Mild impairment (Child-Pugh score 5-6): Consider reducing dose and/or frequency 1

Renal Impairment

• Moderate to severe impairment (GFR <90 mL/min): Reduce dose by 50%
• End-stage renal disease: Avoid bupropion 2, 1

Elderly Patients

• Consider lower starting doses due to increased risk of adverse effects 2

Discontinuation Protocol

• For patients on 300 mg daily, decrease to 150 mg once daily for 1-2 weeks before complete discontinuation
• Gradual tapering is recommended to minimize withdrawal symptoms
• Abrupt discontinuation is not recommended except in cases of serious medical toxicity or confirmed medication diversion 2, 1

Important Monitoring Requirements

• Blood pressure and heart rate: Monitor regularly, especially during first 12 weeks
• Neuropsychiatric symptoms: Watch for anxiety, agitation, insomnia, and suicidal thoughts (particularly in patients under 24 years)
• Seizure risk: Assess for predisposing factors 2

Contraindications

• Uncontrolled hypertension
• History of seizures or conditions lowering seizure threshold
• Current use of MAO inhibitors (allow 14-day washout period)
• Brain metastases
• Concurrent tamoxifen use
• Closed-angle glaucoma
• Current alcohol/substance abuse 2

Common Adverse Effects

• Insomnia
• Dry mouth
• Anxiety/jitteriness
• Decreased appetite
• Headache
• Increased blood pressure and heart rate 2, 3

Clinical Pearls

• Bupropion can be used for multiple indications including MDD, SAD, smoking cessation, and ADHD
• It has a lower risk of sexual dysfunction compared to SSRIs 3, 4
• When switching from other bupropion formulations to XL, maintain the same total daily dose when possible 1
• Bupropion may be combined with SSRIs for treatment-resistant depression or to counteract SSRI-induced sexual dysfunction 2, 4

Remember that bupropion carries a black box warning for increased risk of suicidal thoughts in young adults, requiring careful monitoring, especially during the initial treatment period 2.