What is the recommended protocol for increasing the dosage of bupropion (Wellbutrin) XL?

Protocol for Increasing Bupropion XL Dosage

For increasing the dosage of bupropion XL, start with 150 mg once daily in the morning for 4 days, then increase to the target dose of 300 mg once daily in the morning. 1

Initial Dosing and Titration Schedule

• Bupropion XL (extended-release) should be administered in the morning and may be taken with or without food 1
• The recommended starting dose for Major Depressive Disorder (MDD) is 150 mg once daily in the morning 1
• After 4 days of dosing at 150 mg, the dose may be increased to the target dose of 300 mg once daily in the morning 1
• Bupropion XL tablets should be swallowed whole and not crushed, divided, or chewed to maintain the extended-release properties 1

Maximum Dosing Considerations

• For bupropion XL, the maximum recommended dose is 450 mg per day 2
• To minimize the risk of seizure, it is essential to increase the dose gradually 1
• Doses above 300 mg of bupropion XL were not assessed in seasonal affective disorder trials, suggesting caution when exceeding this dose 1

Special Population Considerations

• For patients with moderate to severe hepatic impairment (Child-Pugh score: 7 to 15), the maximum dose should be limited to 150 mg every other day 1
• For patients with mild hepatic impairment (Child-Pugh score: 5 to 6), consider reducing the dose and/or frequency of dosing 1
• For patients with renal impairment (glomerular filtration rate less than 90 mL/min), consider reducing the dose and/or frequency of bupropion XL 1
• For older adults, lower starting doses (approximately 50% of standard dose) may be appropriate due to increased risk of adverse reactions 2

Monitoring During Dose Increases

• Monitor closely for worsening depression and emergence of suicidal thoughts and behaviors, especially when initiating therapy or changing doses 1
• Watch for common side effects that may occur during dose increases, including insomnia, headache, dry mouth, nausea, and anxiety 3
• Insomnia and dry mouth are the most common side effects that occur significantly more frequently with bupropion SR than with placebo 3
• Be alert for signs of acute dystonia (neck stiffness, trismus, jaw pain), which may be dose-related and require dose reduction 4

Discontinuation Protocol

• When discontinuing treatment in patients taking bupropion XL 300 mg once daily, decrease the dose to 150 mg once daily prior to discontinuation 1
• This tapering approach helps minimize discontinuation symptoms 1

Clinical Pearls

• If a patient experiences intolerable side effects at a higher dose, reducing to 150 mg once daily may still provide therapeutic benefit while minimizing adverse effects 4
• Bupropion has a lower incidence of sexual dysfunction and somnolence compared to some SSRIs, which may be beneficial for certain patients 5
• If no response is seen after 6-8 weeks at an adequate dose, consider alternative treatment 2
• Bupropion should be avoided in patients with seizure disorders as it may lower the seizure threshold 2
• Avoid use with monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuing MAOIs 2