How should Wellbutrin (bupropion) 75 mg be prescribed?

How to Prescribe Wellbutrin 75 mg

Wellbutrin 75 mg is not a standard therapeutic dose for any indication; you should prescribe bupropion SR starting at 150 mg once daily for 3 days, then increase to 150 mg twice daily (300 mg total) for major depressive disorder, or use a gradual titration starting at 37.5 mg daily in older adults or patients requiring cautious dosing. 1

Standard Dosing for Major Depressive Disorder

For bupropion SR (sustained-release), initiate at 150 mg once daily in the morning for the first 3 days, then increase to 150 mg twice daily (300 mg total daily dose) if tolerated. 1 This represents the standard therapeutic regimen for depression. 1

• The maximum dose for bupropion SR is 400 mg per day, while bupropion XL can be dosed up to 450 mg daily. 1
• The typical maintenance dose for depression is 300 mg/day, which is sufficient for most patients. 2
• Full antidepressant efficacy typically emerges at 6–8 weeks after achieving therapeutic dosing. 1

Gradual Titration for Special Populations

For older adults (≥65 years) or patients requiring cautious initiation, start with 37.5 mg every morning, then increase by 37.5 mg every 3 days as tolerated, targeting a maximum of 150 mg twice daily (300 mg total). 1 This approach minimizes adverse reactions in vulnerable populations. 1

• Lower starting doses (approximately 50% of standard dose) are appropriate for older adults due to increased risk of adverse reactions. 1
• The second dose must be administered before 3 PM to minimize insomnia risk. 1, 2
• Bupropion has minimal anticholinergic effects compared to tricyclic antidepressants, making it a preferred option for elderly patients. 1

Dose Adjustments for Hepatic and Renal Impairment

In moderate to severe hepatic impairment, the maximum dose is 150 mg daily (one tablet). 1 Bupropion is extensively metabolized by the liver, and impaired hepatic function leads to drug accumulation. 1

In moderate to severe renal impairment (eGFR <90 mL/min), reduce the total daily dose by 50%. 1 Bupropion and its active metabolites are cleared renally and accumulate when kidney function is reduced. 1

Avoid bupropion entirely in end-stage renal disease or patients on dialysis, as hemodialysis does not effectively clear the primary active metabolite hydroxybupropion. 1

Critical Timing Considerations

• Administer the first dose in the morning to leverage bupropion's activating properties. 1
• Give the second dose before 3 PM to prevent insomnia, particularly in patients on multiple CNS-active medications. 1, 2
• For smoking cessation, begin bupropion 1–2 weeks before the target quit date to allow therapeutic drug levels to be established. 1

Absolute Contraindications

Never prescribe bupropion in patients with:

• Seizure disorders or any condition predisposing to seizures (prior head trauma, brain tumor, stroke), as bupropion lowers the seizure threshold. 1, 2
• Current or recent MAOI use (within 14 days of discontinuation), due to hypertensive crisis risk. 1, 2
• Eating disorders (bulimia or anorexia nervosa), which increase seizure risk. 1
• Abrupt discontinuation of alcohol, benzodiazepines, or antiepileptic drugs, which dramatically increases seizure risk. 1
• Uncontrolled hypertension, as bupropion can elevate blood pressure and heart rate. 1, 2

Seizure Risk and Safety Monitoring

At the standard 300 mg/day dose, the seizure rate is approximately 0.1% (1 in 1,000 patients). 1 This risk increases markedly above 450 mg/day or with rapid dose escalation. 1, 3, 4

• Do not exceed 450 mg/day total to maintain seizure risk at 0.1%. 1
• Screen for seizure risk factors including eating disorders, alcohol withdrawal, or head trauma history. 1, 2
• Gradual titration is necessary to minimize seizure risk while achieving therapeutic levels. 1

Monitoring Requirements

Monitor the following parameters:

• Blood pressure and heart rate, especially during the first 12 weeks, as bupropion can cause elevations. 1, 2
• Suicidal ideation and behavioral changes during weeks 1–2, as the risk of suicide attempts is highest in the first 1–2 months, particularly in patients younger than 24 years. 1
• Agitation or behavioral activation, as bupropion's activating properties can exacerbate agitation. 1, 2

Clinical Advantages

Bupropion offers distinct advantages over SSRIs:

• Significantly lower rates of sexual dysfunction compared to SSRIs like escitalopram and paroxetine. 1
• Minimal weight gain or even weight loss, unlike many other antidepressants. 1
• Lower rates of sedation than SSRIs. 1
• Dual benefit for patients with depression who also want to quit smoking, addressing both conditions simultaneously. 1

Common Pitfalls to Avoid

• Do not use a 75 mg dose as monotherapy—it is subtherapeutic for depression. 1
• Do not skip the intensive monitoring window during weeks 1–2, as this period carries the highest risk for emergent suicidal ideation. 1
• Do not administer the second dose late in the day, as this increases insomnia risk. 1
• Do not discontinue treatment prematurely before 6–8 weeks unless significant adverse effects occur. 1
• Do not combine with MAOIs or initiate within 14 days of MAOI discontinuation. 1, 2

Formulation Differences

Bupropion SR (Wellbutrin SR) is dosed at 150 mg twice daily for a total of 300 mg/day. 1 The SR formulation uses a wax-matrix vehicle that provides slow release throughout the day. 1

Bupropion XL (Wellbutrin XL) is typically administered as 300 mg once daily in the morning. 1 The XL formulation has prolonged absorption with Tmax at approximately 5 hours versus 3 hours for SR. 5

All three formulations (IR, SR, XL) are bioequivalent in terms of systemic exposure to bupropion. 5, 6 However, some generic versions of bupropion SR were historically found not to be bioequivalent to brand-name Wellbutrin SR, so monitor closely when switching formulations. 1