What is the initiation protocol for bupropion (Wellbutrin) in treating major depressive disorder?

From the Guidelines

Bupropion for depression is typically started at 150 mg once daily in the morning using the extended-release formulation (XL or SR), and after 3-4 days of tolerating this dose, it can be increased to the target dose of 300 mg once daily, as recommended by the American College of Physicians 1.

Key Considerations

• The medication should be taken in the morning to minimize sleep disturbances, and patients should avoid taking it too late in the day.
• It's essential to allow 4-6 weeks at the therapeutic dose to assess full effectiveness, though some improvement may be noticed earlier.
• Bupropion works differently from SSRIs by primarily affecting dopamine and norepinephrine rather than serotonin, making it particularly helpful for depression with fatigue, low motivation, or concentration difficulties.
• Patients should be monitored for increased anxiety, insomnia, and seizure risk, especially in those with eating disorders, seizure history, or alcohol withdrawal.

Monitoring and Follow-up

• Clinicians should assess patient status, therapeutic response, and adverse effects of antidepressant therapy on a regular basis beginning within 1 to 2 weeks of initiation of therapy, as advised by the U.S. Food and Drug Administration 1.
• The American College of Physicians recommends that clinicians modify treatment if the patient does not have an adequate response to pharmacotherapy within 6 to 8 weeks of the initiation of therapy for major depressive disorder 1.

Special Considerations

• Bupropion is associated with a lower rate of sexual adverse events than fluoxetine or sertraline, whereas paroxetine has higher rates of sexual dysfunction than fluoxetine, fluvoxamine, nefazodone, or sertraline 1.
• SSRIs are associated with an increased risk for suicide attempts compared with placebo, and patients should be closely monitored for increases in suicidal thoughts and behaviors, especially during the first 1 to 2 months of treatment 1.

From the FDA Drug Label

1. 2 Dosage for Major Depressive Disorder (MDD) The recommended starting dose for MDD is 150 mg once daily in the morning. After 4 days of dosing, the dose may be increased to the target dose of 300 mg once daily in the morning.

To start bupropion for depression, the recommended starting dose is 150 mg once daily in the morning. After 4 days, the dose may be increased to 300 mg once daily in the morning 2.

• Key points:
  • Start with 150 mg once daily
  • Increase to 300 mg after 4 days if necessary
  • Administer in the morning
  • May be taken with or without food
  • Swallow tablets whole, do not crush, divide, or chew 2

From the Research

Starting Bupropion for Depression

To start bupropion for depression, it is essential to understand the medication's properties and usage guidelines.

• Bupropion is a dopamine-norepinephrine reuptake inhibitor and is an effective antidepressant 3.
• It is available as three oral formulations: immediate release (IR), sustained release (SR), and extended/modified release (XR) 3.
• The dosage is typically maintained at 450 mg/day or less in a divided schedule to minimize the risk of seizures 4.

Dosage and Administration

• Bupropion IR is administered three times daily, while SR is administered twice daily, and XR is administered once daily 3.
• All three formulations are bioequivalent in terms of systemic exposure to bupropion 3.
• The medication should be started at a low dose and gradually increased to minimize side effects.

Efficacy and Safety

• Bupropion has been shown to be as effective as tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) in treating major depressive disorder (MDD) 3, 5.
• It is generally well tolerated, with minimal anticholinergic effects and a low risk of cardiac conduction problems 4.
• Common side effects include dry mouth, and it may lower the convulsive threshold, making it not recommended for individuals predisposed to seizures 4.

Special Considerations

• Bupropion may have a modest advantage over SSRIs in treating anxious depression, although the difference is relatively small 6.
• It has been shown to be effective in treating anxiety symptoms in MDD, with comparable efficacy to SSRIs 7.
• The medication should be used with caution in patients with a history of seizures or other conditions that may increase the risk of seizures.