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

Bupropion (Wellbutrin): Indications and Dosing

Bupropion is FDA-approved for major depressive disorder (MDD) and seasonal affective disorder (SAD), with established efficacy for smoking cessation, and should be dosed at 150 mg once daily initially, titrating to 300 mg daily for most indications while avoiding use in patients with seizure disorders or eating disorders. 1

FDA-Approved Indications

• Major Depressive Disorder (MDD): Bupropion is indicated for treatment of MDD as defined by DSM criteria, with efficacy established in controlled trials of adult patients 1
• Seasonal Affective Disorder (SAD): Approved for prevention of seasonal major depressive episodes in patients with autumn-winter seasonal pattern 1
• Smoking Cessation: While the provided FDA label focuses on depression indications, bupropion has demonstrated superior abstinence rates compared to placebo (OR 2.07; 95% CI 1.75-2.45) with efficacy similar to nicotine patch 2

Dosing Guidelines

Major Depressive Disorder

• Starting dose: 150 mg once daily in the morning 1, 3
• Titration: After 4 days, may increase to target dose of 300 mg once daily 1
• Maximum dose: 450 mg per day for XL formulation; 400 mg per day for SR formulation 3, 4
• SR formulation alternative: 150 mg once daily for 3 days, then 150 mg twice daily (300 mg total) 3

Seasonal Affective Disorder

• Starting dose: 150 mg once daily 1
• Titration: After 7 days, may increase to 300 mg once daily 1
• Timing: Initiate in autumn prior to onset of depressive symptoms; continue through winter season 1, 5
• Discontinuation: Taper to 150 mg once daily before stopping in early spring 1

The prevention approach is highly effective—across three trials, bupropion XL reduced depression recurrence rates by 44% relative to placebo (19% vs 30%, 13% vs 21%, and 16% vs 31%) when started while patients were still well 5

Smoking Cessation

• Standard dose: 150 mg twice daily (300 mg total) of SR formulation 2, 3
• Timing: Begin 1-2 weeks before target quit date to establish therapeutic levels 2, 3
• Duration: 7-12 weeks of treatment, with efficacy assessed at end of this period 2, 3
• Special consideration: May be particularly beneficial for patients with comorbid depression 2, 4

Special Population Dosing

Hepatic Impairment

• Moderate to severe impairment (Child-Pugh 7-15): Maximum 150 mg every other day 1, 3
• Mild impairment (Child-Pugh 5-6): Consider reducing dose and/or frequency 1

Renal Impairment

• GFR <90 mL/min: Reduce total daily dose by half due to renal clearance of bupropion and metabolites 1, 3
• Close monitoring required for adverse reactions as drug may accumulate 3

Older Adults

• Starting dose: 37.5 mg every morning 3
• Titration: Increase by 37.5 mg every 3 days as tolerated 3
• Maximum dose: 150 mg twice daily (300 mg total) 3
• Timing consideration: Administer second dose before 3 PM to minimize insomnia 3

Critical Safety Considerations

Absolute Contraindications

• Seizure disorders: Bupropion lowers seizure threshold with 0.1% seizure risk at recommended doses 2, 1
• Brain metastases with seizure history or elevated risk: Must avoid bupropion 2
• Eating disorders (bulimia, anorexia nervosa): Increased seizure risk contraindicates use 1, 3
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs: Contraindicated due to seizure risk 1
• MAOI use: Do not use within 14 days of MAOI discontinuation 1

Important Warnings

• Suicidality: Black box warning for increased risk of suicidal thoughts and behavior in children, adolescents, and young adults; monitor closely for worsening and emergence of suicidal thoughts 1
• Neuropsychiatric effects: While serious events are rare, monitor for mood changes, psychosis, hallucinations, agitation, and anxiety 2
• Cardiovascular safety: Recent meta-analyses show no elevated cardiovascular risk, but monitor blood pressure as bupropion can increase BP 2
• Seizure risk is dose-dependent: Gradual titration is essential; maximum 450 mg/day for XL, 400 mg/day for SR 1, 4

Administration Pearls

• Swallow whole: Extended-release tablets must not be crushed, divided, or chewed 1
• Timing: Administer in the morning; may take with or without food 1
• Tapering: When discontinuing 300 mg daily dose, decrease to 150 mg once daily before stopping 1
• Formulation switching: When switching from immediate-release or SR to XL, use same total daily dose when possible 1

Clinical Efficacy Context

Bupropion demonstrates efficacy comparable to SSRIs with median time to relapse of 44 weeks in MDD 4, 6. Its unique mechanism—dopamine and norepinephrine reuptake inhibition without serotonergic effects—provides advantages including minimal sexual dysfunction, lower rates of weight gain and sedation, and potential benefit in patients with atypical depression 2, 4, 6. The Cochrane review of 44 trials showed relative risk of 1.62 (95% CI 1.49-1.76) for smoking cessation 2.