What is the recommended dose increase for bupropion (Wellbutrin) if 300mg does not provide adequate therapeutic effect?

Bupropion (Wellbutrin) Dosage Adjustment When 300mg Is Ineffective

When bupropion 300mg daily is not providing adequate therapeutic effect, the dose can be increased to a maximum of 450mg daily, divided into multiple doses, with careful monitoring for adverse effects.

Dosing Considerations for Bupropion

Maximum Recommended Dosage

• The maximum FDA-approved daily dose of bupropion is 450mg per day 1
• Doses should be divided (typically 150mg three times daily for immediate release or appropriate divided doses for extended-release formulations)
• Doses exceeding 450mg daily are associated with:
  • Increased seizure risk 2
  • Higher likelihood of manic episodes in bipolar patients 3
  • Greater frequency of adverse effects 2

Titration Protocol

• When increasing from 300mg to 450mg daily:
  • Add the additional 150mg with at least 8 hours between doses
  • For extended-release formulations, follow specific product labeling for divided dosing
  • Allow 1-2 weeks at the new dose to assess therapeutic effect 1

Monitoring Requirements

• Monitor closely for adverse effects when increasing the dose:
  • Seizures (0.4% risk at 450mg daily) 2
  • Agitation (8.2%) 2
  • Dizziness (7.4%) 2
  • Tremor (7.1%) 2
  • Insomnia (common at higher doses) 1

Special Considerations

Timing of Doses

• Take the last daily dose before 3 p.m. to minimize insomnia risk 1
• Space doses evenly throughout the day to maintain steady blood levels

When Maximum Dose Is Ineffective

If 450mg daily for 4 weeks does not provide adequate response:

1. Consider switching to an alternative antidepressant class (SSRI, SNRI)
2. Consider augmentation strategies with other agents 1
3. Evaluate for comorbid conditions that may be affecting treatment response

Contraindications to Dose Increases

Do not increase beyond 300mg daily if:

• History of seizures or seizure disorder
• Current eating disorder
• Abrupt discontinuation of alcohol or sedatives
• Concurrent medications that lower seizure threshold
• History of head trauma or CNS tumors 1, 2

Common Pitfalls

• Exceeding maximum dose: Never exceed 450mg daily due to exponentially increased seizure risk 4, 2
• Inadequate trial period: Allow at least 4 weeks at the maximum dose before determining lack of efficacy 1
• Ignoring drug interactions: Check for medications that may interact with bupropion before increasing dose
• Missing bipolar disorder: Higher doses of bupropion (>450mg) have been associated with triggering manic episodes 3

Remember that bupropion is used for various indications including depression, ADHD, and smoking cessation 5, 6, but the maximum recommended dose remains 450mg daily regardless of indication.