What is the recommended cross-tapering regimen from sertraline (Selective Serotonin Reuptake Inhibitor) 125mg to bupropion (Norepinephrine-Dopamine Reuptake Inhibitor)?

Cross-Tapering from Sertraline 125mg to Bupropion: Recommended Schedule

For most patients, a direct switch approach is recommended: discontinue sertraline 125mg and start bupropion SR 150mg once daily on the same day, then increase bupropion to 150mg twice daily after 3-4 days if tolerated. 1

Week-by-Week Cross-Taper Schedule

Week	Sertraline Dose	Bupropion SR Dose	Key Monitoring Points
Day 1	STOP 125mg	START 150mg once daily (morning)	Monitor for withdrawal symptoms [1]
Days 4-7	Discontinued	150mg twice daily (morning & before 3 PM)	Assess tolerability before increasing [1]
Weeks 2-8	Discontinued	Continue 150mg twice daily	Monitor efficacy and side effects [1]
Week 6-8	N/A	Evaluate response; consider dose adjustment if needed	Allow 6-8 weeks at adequate dose [2]

Rationale for Direct Switch Approach

• Sertraline's pharmacokinetic profile supports abrupt discontinuation at therapeutic doses without requiring gradual taper in most cases, as the 50mg starting dose is typically the optimal therapeutic dose 3

• Alternate-day dosing during taper should be avoided, as recent pharmacokinetic modeling demonstrates this approach causes pronounced receptor occupancy variation and significantly increases withdrawal symptom risk 4

• The direct switch minimizes the period without adequate antidepressant coverage while avoiding polypharmacy complications during transition 1

Critical Timing and Administration Details

• First bupropion dose must be taken in the morning to leverage its activating properties and minimize insomnia risk 2, 5

• Second daily dose (after titration to twice daily) must be administered before 3 PM to prevent sleep disturbances, which is the most common side effect 2, 1, 5

• Do not crush, divide, or chew bupropion SR tablets, as this increases seizure risk by altering the sustained-release mechanism 1

Absolute Contraindications Before Initiating Bupropion

• Seizure disorders or conditions lowering seizure threshold - bupropion reduces seizure threshold with 0.1% risk at standard doses 6, 1

• Eating disorders (bulimia or anorexia nervosa) - significantly increased seizure risk in this population 2, 5

• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs - dramatically increases seizure risk 2

• Uncontrolled hypertension - bupropion can elevate blood pressure and requires baseline monitoring 1, 5

• Current MAOI use or within 14 days of MAOI discontinuation - risk of hypertensive crisis 2

Special Population Dose Adjustments

Older Adults (≥55 years)

• Start with 37.5mg once daily in the morning, increase by 37.5mg every 3 days as tolerated 2, 5
• Maximum dose: 150mg twice daily (300mg total daily) 2, 5
• Lower starting doses minimize adverse reaction risk in this population 2

Renal Impairment (GFR <90 mL/min)

• Reduce total daily dose by half due to accumulation of bupropion and metabolites 2, 1, 5
• Requires close monitoring for adverse reactions 2

Hepatic Impairment (Moderate to Severe)

• Maximum dose: 150mg daily (one tablet) 2
• Significantly impaired metabolism necessitates dose reduction 2

Monitoring Requirements During Transition

First 2 Weeks (Critical Period)

• Monitor for sertraline withdrawal symptoms: dizziness, paresthesias, anxiety, irritability, though these are less common with direct switch 1

• Monitor for bupropion activation effects: agitation, anxiety, insomnia, particularly in first week 2, 5

• Check blood pressure at baseline and during titration - essential given bupropion's potential to elevate BP 1, 5

Weeks 2-8 (Efficacy Assessment Period)

• Monitor for neuropsychiatric symptoms, especially in patients <24 years old: suicidal ideation, mood changes, agitation 1, 5

• Assess for common side effects: insomnia (most common), dry mouth, headache, nausea 2

• Evaluate antidepressant response after 6-8 weeks at adequate dosing - if no response, consider alternative strategies 2, 1

Clinical Advantages of This Transition

• Bupropion has significantly lower rates of sexual dysfunction compared to sertraline - only 15% of men and 7% of women develop sexual dysfunction with bupropion SR versus 63% of men and 41% of women with sertraline 7, 8

• Orgasmic dysfunction specifically is markedly reduced with bupropion compared to sertraline throughout treatment 8

• Weight neutrality: bupropion causes minimal weight changes (-1.06 kg) similar to sertraline (-0.79 kg), making it appropriate for patients concerned about weight gain 8

• Activating properties benefit patients with low energy, apathy, or hypersomnia - common residual symptoms that may have persisted on sertraline 2

Common Pitfalls to Avoid

• Do not use gradual sertraline taper unless patient has history of severe withdrawal symptoms - this unnecessarily prolongs transition and increases complexity 1

• Do not dose bupropion late in the day - this is the primary cause of insomnia, the most common side effect 2, 1, 5

• Do not increase bupropion dose before 3-4 days - allow time to assess tolerability before titration 1

• Do not exceed 300mg daily for standard depression treatment - maximum dose is 450mg daily, but seizure risk increases with higher doses 2

• Do not combine with tamoxifen - bupropion may reduce tamoxifen efficacy through CYP2D6 inhibition 5

When to Consider Alternative Strategies

• If patient has history of severe SSRI discontinuation syndrome: Consider brief overlap (3-7 days) with gradual sertraline reduction while initiating bupropion, though this is not standard practice 1

• If patient develops intolerable activation or insomnia: Reduce bupropion to 150mg once daily and reassess after 1 week before attempting further titration 2

• If no response after 8 weeks at 300mg daily: Consider alternative antidepressant or augmentation strategies rather than increasing bupropion dose 2, 1