What is the proper usage and dosage of Wellbutrin (bupropion) for treating depression?

Wellbutrin (Bupropion) for Depression: Dosing and Administration

Starting Dose and Titration

For major depressive disorder, start bupropion XL at 150 mg once daily in the morning, then increase to the target dose of 300 mg once daily after 4 days if tolerated. 1

For patients requiring more cautious titration (older adults, those on multiple medications, or those at higher risk for adverse effects):

• Begin with 37.5 mg once daily in the morning 2
• Increase by 37.5 mg every 3 days as tolerated 2
• Target the standard therapeutic dose of 150-300 mg daily 2

The maximum daily dose is 450 mg for bupropion XL to minimize seizure risk. 1

Formulation-Specific Dosing

Bupropion XL (Extended Release)

• Initial dose: 150 mg once daily in the morning 2, 1
• Maintenance dose: 150-300 mg once daily 2
• Maximum dose: 450 mg once daily 2, 1

Bupropion SR (Sustained Release)

• Initial dose: 150 mg once daily for 3 days 2
• Maintenance dose: 150 mg twice daily (300 mg total) 2
• Maximum dose: 400 mg per day 2
• Critical timing: Administer the second dose before 3 PM to minimize insomnia risk 2

Special Population Dosing

Hepatic Impairment

• Moderate to severe hepatic impairment: 150 mg every other day (maximum) 2, 1
• Mild hepatic impairment: Consider reducing dose and/or frequency 1

Renal Impairment

• GFR <90 mL/min: Reduce total daily dose by half 2, 1
• Close monitoring for adverse reactions is required as bupropion and metabolites accumulate with renal dysfunction 2

Older Adults

• Start with 37.5 mg every morning 2
• Increase by 37.5 mg every 3 days as tolerated 2
• Maximum dose: 150 mg twice daily (300 mg total) 2

Absolute Contraindications

Do not prescribe bupropion in patients with:

• Seizure disorder or any condition lowering seizure threshold 1
• Current or prior diagnosis of bulimia or anorexia nervosa (increased seizure risk) 2, 1
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs 1
• Concurrent MAOI use or within 14 days of MAOI discontinuation 1
• Known hypersensitivity to bupropion 1
• Uncontrolled hypertension 2

Monitoring and Timeline to Response

Initial Monitoring (Weeks 1-2)

• Monitor closely for suicidal ideation, especially in patients <24 years old (black box warning) 2, 1
• The greatest risk for suicide attempts occurs during the first 1-2 months of treatment 2
• Check blood pressure and heart rate, as bupropion can elevate both 2
• Assess for neuropsychiatric symptoms: agitation, anxiety, mood changes, psychosis 2, 1

Efficacy Assessment (Weeks 6-8)

• Allow 6-8 weeks at an adequate therapeutic dose before determining treatment response 2
• Energy levels may improve more rapidly, sometimes within the first few weeks 2
• If no adequate response by 6-8 weeks, modify the treatment approach 2

Ongoing Monitoring

• Periodically reassess dose and need for maintenance treatment 1
• Monitor blood pressure throughout treatment, especially during the first 12 weeks 2

Clinical Advantages and Patient Selection

Bupropion is particularly beneficial for patients with:

• Depression characterized by low energy, apathy, or hypersomnia (due to activating properties) 2
• Concerns about sexual dysfunction (lower rates than SSRIs) 2, 3
• Concerns about weight gain (less weight gain than many antidepressants) 3, 4, 5
• Comorbid smoking cessation goals 2

Seasonal Affective Disorder

For prevention of seasonal affective disorder:

• Initiate treatment in autumn prior to onset of symptoms 1, 6
• Starting dose: 150 mg once daily 1
• After one week, may increase to 300 mg once daily 1
• Continue treatment through the winter season 1
• Bupropion XL reduces recurrence risk by 44% compared to placebo 6

Critical Safety Considerations

Seizure Risk

The risk is dose-related and can be minimized by:

• Gradual dose titration 1
• Not exceeding maximum daily doses (450 mg XL, 400 mg SR) 2, 1
• Avoiding use in patients with predisposing factors 1
• Discontinue immediately if seizure occurs 1

Neuropsychiatric Effects

Monitor for and instruct patients to report:

• Changes in mood (depression, mania) 1
• Psychosis, hallucinations, paranoia, delusions 1
• Agitation, anxiety, panic attacks 1
• Suicidal ideation or behavior 1

Drug Interactions

• CYP2B6 inducers (ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, phenytoin) may require dose increase, but do not exceed maximum recommended dose 1
• Bupropion inhibits CYP2D6, raising concern for clinically relevant interactions 3

Augmentation Strategy

When augmenting SSRIs with bupropion, this combination decreases depression severity more effectively than augmentation with buspirone (addresses complementary mechanisms: serotonin via SSRI, norepinephrine/dopamine via bupropion) 2

Formulation Switching Considerations

When switching between brand and generic formulations or between SR and XL:

• Monitor patients closely for loss of antidepressant effect 2
• Historical bioequivalence issues with some generic bupropion SR formulations have been documented 2