What are the indications and dosing guidelines for Bupropion (Wellbutrin)?

Indications and Dosing Guidelines for Bupropion (Wellbutrin)

Bupropion is FDA-approved for the treatment of major depressive disorder (MDD) and prevention of seasonal affective disorder (SAD), with specific dosing guidelines that should be followed to minimize seizure risk and optimize therapeutic outcomes. 1

Indications

Major Depressive Disorder (MDD)

• Primary FDA-approved indication 1
• Efficacy established in multiple controlled trials of adult patients with MDD 1
• Effective for both acute treatment and maintenance therapy 1, 2

Seasonal Affective Disorder (SAD)

• FDA-approved for prevention of seasonal major depressive episodes 1
• Should be initiated in autumn prior to onset of seasonal depressive symptoms 1
• Has demonstrated a 44% relative risk reduction in seasonal depression recurrence compared to placebo 3

Dosing Guidelines

General Dosing Principles

• Always increase dose gradually to minimize seizure risk 1
• Tablets should be swallowed whole, not crushed, divided, or chewed 1
• Administer in the morning with or without food 1

Dosing for Major Depressive Disorder

• Starting dose: 150 mg once daily in the morning 1
• After 4 days, may increase to target dose of 300 mg once daily 1
• Maximum recommended daily dose: 450 mg 4

Dosing for Seasonal Affective Disorder

• Starting dose: 150 mg once daily 1
• After 7 days, may increase to target dose of 300 mg once daily 1
• Doses above 300 mg were not assessed in SAD trials 1
• Continue through winter season and taper in early spring 1
• For patients on 300 mg daily, decrease to 150 mg once daily before discontinuation 1

Special Populations

Hepatic Impairment

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

Renal Impairment

• For moderate to severe renal impairment, reduce dose by 50% 4
• Consider reducing dose and/or frequency in patients with GFR <90 mL/min 1
• Avoid in end-stage renal disease 4

Discontinuation

• Gradual tapering is recommended when discontinuing bupropion 4, 1
• For patients on 300 mg daily, decrease to 150 mg once daily for 1-2 weeks before complete discontinuation 4, 1
• More cautious tapering should be considered for long-term users, those on higher doses (≥300 mg daily), patients with history of withdrawal symptoms, and those with comorbid anxiety disorders 4

Contraindications

• Seizure disorder 1
• Current or prior diagnosis of bulimia or anorexia nervosa 1
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs 1
• Concomitant use of MAOIs (allow 14-day washout period between MAOIs and bupropion) 4, 1
• Uncontrolled hypertension 4
• Known hypersensitivity to bupropion or other ingredients 1
• Brain metastases, tamoxifen, and closed-angle glaucoma 4

Safety Considerations

Black Box Warning

• Increased risk of suicidal thoughts and behavior in children, adolescents, and young adults 1
• Monitor closely for worsening and emergence of suicidal thoughts and behaviors 1

Common Adverse Effects

• Dry mouth, insomnia, headache, nausea, dizziness 4, 1, 2
• Anxiety/jitteriness, decreased appetite 4
• Stimulating properties that may exacerbate underlying anxiety symptoms 4

Serious Adverse Effects

• Seizures (dose-related risk) 4, 1, 5
• Increased blood pressure and heart rate 4
• Severe skin reactions or anaphylaxis 4
• Neuropsychiatric symptoms 4, 1

Monitoring Recommendations

• Regular monitoring of blood pressure and heart rate, especially during first 12 weeks 4
• Monitor for anxiety, agitation, insomnia 4
• Increased vigilance for suicidal thoughts, especially in patients under 24 years 4, 1

Drug Interactions

• Contraindicated with MAOIs 4, 1
• Use caution with medications that lower seizure threshold 6
• Inhibits CYP2D6 and may reduce clearance of agents metabolized by this enzyme 7
• Metabolized by CYP2B6; dose adjustments may be needed with CYP2B6 inducers 1

Bupropion offers a unique mechanism of action as a dopamine and norepinephrine reuptake inhibitor, making it a valuable option for patients who may not respond to or tolerate other antidepressants 6, 2.