What is the recommended dosage and usage of Bupropion (Wellbutrin) for treating major depressive disorder and smoking cessation?

Bupropion Dosing and Administration

Major Depressive Disorder

For major depressive disorder, start bupropion SR at 150 mg once daily for 3 days, then increase to 150 mg twice daily (300 mg total daily dose), or use bupropion XL 150 mg once daily initially, increasing to 300 mg once daily after 4 days if tolerated. 1, 2

Standard Dosing Regimen

• Bupropion SR (Sustained Release): Begin with 150 mg once daily for the first 3 days, then escalate to 150 mg twice daily (300 mg total) 1
• Bupropion XL (Extended Release): Start at 150 mg once daily, then increase to 300 mg once daily after 4 days 2
• The maximum dose for SR formulation is 400 mg per day, while XL formulation has a maximum of 450 mg per day 1

Timing of Administration

• Administer the first dose in the morning to leverage bupropion's activating properties 1
• For SR formulation taken twice daily, give the second dose before 3 PM to minimize insomnia risk 1
• XL formulation should be taken once daily in the morning 1

Efficacy Assessment

• If no response is observed after 6-8 weeks at an adequate dose, consider alternative treatment 1
• Periodically reassess the dose and need for maintenance treatment 2

Smoking Cessation

For smoking cessation, initiate bupropion SR 1-2 weeks before the target quit date at 150 mg once daily for days 1-3, then increase to 150 mg twice daily (300 mg total) for 7-12 weeks. 3

Dosing Protocol

• Begin dosing 1-2 weeks prior to the target quit date to establish therapeutic drug levels before cessation attempts 3, 1
• Days 1-3: 150 mg orally once daily 3
• Day 4 through week 12: 150 mg orally twice daily if tolerated 3
• Maximum dose: 300 mg per day for smoking cessation 3

Treatment Duration

• Standard treatment duration is 7-12 weeks 3, 1
• Therapy may be extended to promote continued cessation (6 months to 1 year) while attempting to avoid longer periods if possible 3
• Assess efficacy after 7-12 weeks of treatment 1

Clinical Advantages

• Bupropion may be particularly beneficial for patients with comorbid depression who want to quit smoking, addressing both conditions simultaneously 1, 4
• Combining bupropion with naltrexone can help with smoking cessation while mitigating associated weight gain 1

Special Population Adjustments

Hepatic Impairment

• Moderate to severe hepatic impairment: Maximum dose of 150 mg daily (one tablet) or 150 mg every other day 1, 2
• Mild hepatic impairment: Consider reducing the dose and/or frequency of dosing 2

Renal Impairment

• For moderate to severe renal impairment (GFR <90 mL/min), reduce the total daily dose by half 1, 2
• Close monitoring for adverse reactions is required as bupropion and its metabolites are cleared renally and may accumulate 1

Older Adults

• Start with 37.5 mg every morning for older adults 1, 5
• Gradually increase by 37.5 mg every 3 days as tolerated 1, 5
• Maximum dose: 150 mg twice daily (300 mg total daily dose) 1, 5
• Administer the second dose before 3 PM to prevent sleep disturbances 1
• Lower starting doses (approximately 50% of standard dose) are appropriate due to increased risk of adverse reactions 1

Critical Safety Considerations

Absolute Contraindications

• Seizure disorders: Bupropion lowers the seizure threshold; risk is dose-related and increases at higher doses 3, 2
• Current or prior diagnosis of bulimia or anorexia nervosa due to increased seizure risk 2
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs 2
• Patients with brain metastases due to seizure risk 3
• Closed-angle glaucoma 3
• Concurrent use with MAO inhibitors or within 14 days of discontinuing MAOIs due to increased risk of hypertensive reactions 3, 2
• Patients taking tamoxifen 3

Neuropsychiatric Monitoring

• Monitor for the development or worsening of serious neuropsychiatric issues including depression, suicidal ideation/behavior, hostility, agitation, and psychosis 3, 2
• This monitoring is essential even in patients without a previous psychiatric history 3
• Discontinue use if these signs occur 3
• Increased risk of suicidal thinking and behavior exists in children, adolescents, and young adults taking antidepressants 2
• Patients should be monitored particularly in individuals younger than 24 years 1

Cardiovascular Monitoring

• Monitor blood pressure before initiating treatment and periodically during treatment, as bupropion can increase blood pressure 1, 2
• Avoid in patients with uncontrolled hypertension 1

Bipolar Disorder Precautions

• Screen patients for bipolar disorder before initiating treatment 2
• Monitor closely for signs of hypomania or mania, particularly in the first 24-48 hours after any dose changes and during the first several weeks of treatment 5
• Watch for neuropsychiatric adverse effects, especially agitation, insomnia, or increased energy that could signal an emerging manic episode 5

Common Adverse Effects

• Most common adverse reactions (incidence ≥5%; ≥2× placebo rate) include: dry mouth, nausea, insomnia, dizziness, pharyngitis, abdominal pain, agitation, anxiety, tremor, palpitation, sweating, tinnitus, myalgia, anorexia, urinary frequency, and rash 2
• Side effects are generally minimal and considered an acceptable risk compared to smoking 3
• Serious side effects are extremely rare 3
• A multicenter RCT found that rates of neuropsychiatric adverse events in individuals receiving bupropion were not significantly increased relative to those receiving nicotine patches or placebo in both psychiatric and non-psychiatric cohorts 3

Drug Interactions

• Bupropion is a cytochrome P450 2D6 inhibitor; exercise caution when coprescribing with drugs cleared by this enzyme 4
• CYP2B6 inducers (e.g., ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, phenytoin) may require dose increases, but should not exceed the maximum recommended dose 2
• Avoid coprescribing with drugs that lower seizure threshold 4

Clinical Pearls

• Gradual dose titration is necessary to minimize seizure risk while achieving therapeutic levels 1
• The maximum dose should not exceed 450 mg per day to minimize seizure risk 1
• Bupropion has activating properties that can improve energy levels and reduce apathy, making morning administration ideal 1
• Unlike other antidepressants, bupropion has no serotonergic activity and is associated with less somnolence, weight gain, and sexual dysfunction compared to SSRIs and some TCAs 6, 7