What is the highest dose of bupropion (Wellbutrin) that can be given?

Maximum Bupropion (Wellbutrin) Dosing Guidelines

The maximum dose of bupropion (Wellbutrin) is 450 mg per day for the immediate-release formulation, 400 mg per day for the sustained-release (SR) formulation, and 450 mg per day for the extended-release (XL) formulation. 1

Formulation-Specific Maximum Dosing

• Immediate-release (IR): Maximum 450 mg per day, typically divided into three doses 1
• Sustained-release (SR): Maximum 400 mg per day, typically divided into two doses 1
• Extended-release (XL): Maximum 450 mg per day, administered once daily in the morning 1

Safety Considerations for Maximum Dosing

• The primary concern with higher doses is increased seizure risk, which is dose-dependent 2, 3
• Doses exceeding recommended maximums significantly increase seizure risk, with reports of seizures occurring even at therapeutic doses 4, 5
• Seizures have been reported in approximately one-third of overdose cases 6
• Doses of 2.7g and higher can lead to severe complications including seizures, encephalopathy, and cardiovascular effects 3

Dose Adjustments for Special Populations

• Hepatic Impairment:

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

• Renal Impairment:

  • For moderate to severe renal impairment: Total daily dose should be reduced by 50% 1
  • Monitor closely for adverse reactions that could indicate high bupropion or metabolite exposures 6

• Older Adults:

  • Maximum recommended dose is 150 mg twice daily (300 mg total) 1
  • Start with lower doses (approximately 50% of standard dose) and titrate slowly 1

Contraindications for Maximum Dosing

• Seizure disorders (absolute contraindication) 1, 6
• Concurrent use of MAOIs or within 14 days of discontinuing MAOIs 1, 6
• Bulimia or anorexia nervosa (increased seizure risk) 1
• Abrupt discontinuation of alcohol, benzodiazepines, or antiepileptic drugs 1
• Uncontrolled hypertension 7, 1

Clinical Pearls for High-Dose Therapy

• Bupropion should be titrated gradually to reduce seizure risk 5
• For SR formulation, administer second dose before 3 p.m. to minimize insomnia 1
• The maximum dose of 450 mg should never be exceeded, even in treatment-resistant cases 1, 2
• Monitor for neuropsychiatric adverse effects, especially in individuals younger than 24 years 1
• When used in combination with naltrexone (as in weight management), maintain standard maximum dosing guidelines 7, 1

Warning Signs of Toxicity at Maximum Doses

• Hallucinations, mental status changes, loss of consciousness 6
• Sinus tachycardia, ECG changes, conduction disturbances, arrhythmias 6
• Clonus, myoclonus, hyperreflexia 6
• Increased agitation, restlessness, or anxiety 2