What is the appropriate bupropion dosing regimen as adjunctive therapy for SSRI‑induced sexual dysfunction in a 45‑year‑old male?

Bupropion Dosing for SSRI-Induced Sexual Dysfunction

For a 45-year-old male with SSRI-related sexual dysfunction, add bupropion SR 150 mg once daily in the morning, then increase to 150 mg twice daily (300 mg total) after 3–4 days if tolerated, with the second dose administered before 3 PM to minimize insomnia risk. 1, 2

Initial Dosing Protocol

• Start bupropion SR 150 mg once daily in the morning for the first 3–4 days to assess tolerability and minimize adverse effects 1, 2
• Increase to 150 mg twice daily (total 300 mg/day) after the initial titration period if the patient tolerates the starting dose 1, 2, 3
• Administer the second dose before 3 PM to reduce the risk of insomnia, which is a common activating side effect of bupropion 1, 2, 3

Expected Timeline for Improvement

• Most improvement in sexual function (>50%) occurs within the first 2 weeks of bupropion treatment, often at doses of 100–200 mg/day 4
• Formal efficacy assessment should occur at 6–8 weeks at therapeutic dosing before considering treatment modification 1, 2, 3
• Continue the SSRI at its current dose while adding bupropion; do not discontinue or reduce the SSRI if depression is well-controlled 1

Evidence for Efficacy

• Open-label studies show global response rates of 66–75% for reversing SSRI-induced sexual dysfunction with bupropion SR at doses up to 300 mg/day 4, 5
• Bupropion successfully reversed 69% of sexual complaints (including erectile dysfunction, delayed ejaculation, and anorgasmia) in patients receiving SRIs 5
• However, one placebo-controlled trial found no significant benefit with a fixed 150 mg/day dose, suggesting that higher doses (up to 300 mg/day) may be necessary for efficacy 6

Critical Safety Screening Before Initiation

Absolute contraindications that must be ruled out before prescribing bupropion:

• Seizure history or any condition predisposing to seizures (head trauma, brain tumor, stroke) because bupropion lowers the seizure threshold 1, 2, 3
• Current or recent MAOI use (within 14 days) due to risk of hypertensive crisis 1
• Eating disorders (bulimia or anorexia nervosa) because of increased seizure risk 1, 2
• Abrupt discontinuation of alcohol, benzodiazepines, or antiepileptic drugs within the past 2 weeks 1, 2
• Uncontrolled hypertension because bupropion can elevate blood pressure 1, 2, 3

Monitoring Parameters

• Blood pressure and heart rate should be checked at baseline and monitored periodically, especially during the first 12 weeks, as bupropion can cause modest elevations 1, 3
• Neuropsychiatric symptoms including agitation, restlessness, and behavioral changes should be assessed, particularly in patients under 24 years old 1, 3
• Suicidal ideation requires close monitoring in the first 1–2 months, especially in younger patients, due to the FDA black-box warning for all antidepressants 1, 3

Dose Adjustments for Special Populations

• Moderate to severe renal impairment (GFR <90 mL/min): Reduce total daily dose by 50% (e.g., maximum 150 mg/day) because bupropion metabolites accumulate renally 1, 2, 3
• Moderate to severe hepatic impairment: Maximum dose should not exceed 150 mg/day 1, 3
• Older adults: Start with 37.5 mg daily and increase by 37.5 mg every 3 days as tolerated, with a maximum of 150 mg twice daily 1, 2

Maximum Dosing and Seizure Risk

• Do not exceed 450 mg/day total to maintain seizure risk at approximately 0.1% (1 in 1,000 patients) 1, 3
• For adjunctive therapy targeting sexual dysfunction, the standard therapeutic dose is 300 mg/day (150 mg twice daily), which balances efficacy and safety 1, 4, 5

Clinical Advantages of This Approach

• Bupropion has significantly lower rates of sexual dysfunction compared to SSRIs, making it an ideal augmenting agent for this indication 1, 7, 8
• The combination addresses both depression and sexual dysfunction through complementary mechanisms—SSRIs affect serotonin while bupropion works via noradrenergic/dopaminergic pathways 1
• Bupropion augmentation has lower discontinuation rates (12.5%) compared to other augmentation strategies like buspirone (20.6%), indicating superior tolerability 1

Common Pitfalls to Avoid

• Do not use a fixed 150 mg/day dose as the sole therapeutic dose; the placebo-controlled trial showing no benefit used only this lower dose, whereas open-label studies demonstrating efficacy titrated up to 300 mg/day 6, 4
• Do not administer the second dose late in the day (after 3 PM) as this significantly increases insomnia risk 1, 2, 3
• Do not discontinue treatment before 6–8 weeks unless significant adverse effects occur, as sexual function improvement may take several weeks to manifest fully 1, 2, 3