What is the use and dosage of Bupropion (Wellbutrin)?

Bupropion (Wellbutrin): Uses and Dosage

Bupropion is an effective antidepressant medication with multiple therapeutic applications including major depressive disorder, seasonal affective disorder, and smoking cessation, with standard dosing of 150-300 mg daily depending on the formulation and indication. 1

Primary Indications

• Major Depressive Disorder (MDD)

  • Starting dose: 150 mg once daily (XL/extended-release formulation) 1
  • Target dose: 300 mg once daily 1
  • After 4 days, may increase to 300 mg once daily 1
  • Maximum dose: 450 mg per day 2

• Seasonal Affective Disorder (SAD)

  • Initiate treatment in autumn prior to onset of seasonal symptoms 1
  • Starting dose: 150 mg once daily 1
  • After one week, may increase to 300 mg once daily 1
  • Continue treatment through winter season 1, 3
  • Preventive treatment has shown 44% relative risk reduction in seasonal depression recurrence 3

• Smoking Cessation

  • Initiate dosing 1-2 weeks prior to quit date 2
  • Days 1-3: 150 mg orally once daily 2
  • Day 4-12 weeks: 150 mg orally twice daily (if tolerated) 2
  • Treatment duration: 7-12 weeks 2
  • May be extended to promote continued cessation (6 months to 1 year) 2

Available Formulations

• Immediate Release (IR): Administered three times daily 4
• Sustained Release (SR): Administered twice daily 4
  • Starting dose: 100-150 mg daily 2
  • Maintenance dose: 100-150 mg twice daily 2
• Extended/Modified Release (XL/XR): Administered once daily 4
  • Starting dose: 150 mg daily 2
  • Maintenance dose: 150-300 mg daily 2

Special Clinical Considerations

Dosage Adjustments

• Hepatic Impairment 1

  • Moderate to severe: 150 mg every other day
  • Mild: Consider reducing dose and/or frequency

• Renal Impairment 1

  • Consider reducing dose and/or frequency

• When Combined with Naltrexone for Weight Management 2

  • Available as tablets containing 8 mg naltrexone and 90 mg bupropion
  • Titration schedule:
    • 1 tablet daily in morning
    • Weekly escalation to 1 tablet twice daily
    • Then 2 tablets in morning and 1 in afternoon
    • Maintenance dose: 2 tablets twice daily
  • Second dose should not be taken late in day to minimize insomnia risk

Contraindications 1, 2

• Seizure disorder 1
• Current or prior diagnosis of bulimia or anorexia nervosa 1
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, antiepileptic drugs 1
• Monoamine Oxidase Inhibitors (MAOIs): Do not use within 14 days of starting/stopping MAOIs 1
• Known hypersensitivity to bupropion or other ingredients 1
• Patients with brain metastases due to seizure risk 2
• Patients taking tamoxifen 2
• Closed-angle glaucoma 2

Side Effects and Monitoring

• Common side effects (incidence ≥5%; ≥2× placebo rate): 1

  • Dry mouth, nausea, insomnia, dizziness, pharyngitis, abdominal pain, agitation, anxiety, tremor, palpitation, sweating, tinnitus, myalgia, anorexia, urinary frequency, rash

• Important warnings:

  • Seizure risk: Dose-related; minimize by limiting daily dose to 450 mg and gradually increasing dose 1
  • Neuropsychiatric effects: Monitor for depression, mania, psychosis, hallucinations, paranoia, suicidal ideation 1
  • Hypertension: Monitor blood pressure before and during treatment 1
  • Activation of mania/hypomania: Screen patients for bipolar disorder 1

• Advantages over other antidepressants:

  • Less sexual dysfunction than SSRIs 4, 5
  • Less somnolence than TCAs and some SSRIs 4, 5
  • Less weight gain than TCAs 4

Clinical Pearls

• Bupropion is presumed to work as a dopamine-norepinephrine reuptake inhibitor 6, 4
• May be beneficial for patients with depression and concurrent need for smoking cessation 2
• Can be used in combination with NRT (nicotine replacement therapy) for smoking cessation 2
• May be particularly useful for patients with depression and low energy/motivation due to its activating properties 2
• When used for weight management with naltrexone, discontinue if patient hasn't lost 5% of body weight after 12 weeks 2
• When used for smoking cessation, discontinue if patient hasn't quit after 12 weeks 2
• Should be discontinued before procedures requiring opioid use due to naltrexone component (when used in combination) 2

Drug Interactions

• Inhibits CYP2D6, raising concern for clinically relevant drug interactions 6
• Avoid use with MAOIs or within 14 days of stopping MAOIs 1
• Dose increase may be necessary if coadministered with CYP2B6 inducers (e.g., ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, phenytoin) 1