What is the best approach to switch a patient from bupropion (Bupropion) 450 mg to Auvelity (dextromethorphan/bupropion)?

Switching from Bupropion 450 mg to Auvelity (Dextromethorphan/Bupropion)

When switching from bupropion 450 mg to Auvelity, reduce the standalone bupropion dose to account for the 105 mg of bupropion contained in each Auvelity tablet (210 mg total daily when taking the standard twice-daily dosing), then initiate Auvelity using a direct cross-taper approach without a washout period. 1, 2

Understanding the Bupropion Content in Auvelity

• Auvelity contains 45 mg dextromethorphan combined with 105 mg bupropion per tablet 2, 3
• The standard Auvelity dosing is one tablet twice daily, providing 210 mg total daily bupropion 2, 3
• Your patient is currently on 450 mg bupropion daily, which exceeds the bupropion content in standard-dose Auvelity by 240 mg 1

Recommended Switching Strategy

Step 1: Calculate the Bupropion Gap

• Current dose: 450 mg bupropion daily 1
• Bupropion in Auvelity (2 tablets daily): 210 mg 2
• Gap to bridge: 240 mg bupropion 1

Step 2: Direct Cross-Taper Approach

• Since both medications contain bupropion, no washout period is required 4
• Begin Auvelity at one tablet twice daily (morning and early afternoon, before 3 PM to minimize insomnia) 1
• Simultaneously reduce standalone bupropion to 300 mg daily (either as XL once daily or SR 150 mg twice daily) for 3-7 days 1, 4
• After 3-7 days, reduce standalone bupropion to 150 mg daily for another 3-7 days 1, 4
• After this second reduction period, discontinue standalone bupropion entirely and continue Auvelity alone 4

Step 3: Monitor Total Daily Bupropion Exposure

• During the initial cross-taper, total bupropion will be 510 mg daily (210 mg from Auvelity + 300 mg standalone), which exceeds the maximum recommended 450 mg 1, 5
• This brief period of higher exposure (3-7 days) carries increased seizure risk (approximately 0.4% at doses >450 mg) but is necessary to prevent withdrawal symptoms 1, 5
• After the first reduction, total bupropion will be 360 mg daily (210 mg from Auvelity + 150 mg standalone), which is within safe limits 1

Critical Safety Considerations

Seizure Risk Management

• The maximum recommended bupropion dose is 450 mg daily to maintain seizure risk at 0.1% 1, 5
• During the brief period of 510 mg total daily bupropion, screen for seizure risk factors: history of seizure disorder, eating disorders (bulimia/anorexia), abrupt alcohol or benzodiazepine discontinuation, head trauma, or concurrent medications that lower seizure threshold 1, 5
• If any of these risk factors are present, use a more conservative taper with longer intervals between dose reductions 1, 4

Timing of Doses

• Administer the first Auvelity dose in the morning 1
• Administer the second Auvelity dose before 3 PM to minimize insomnia risk, as both bupropion and dextromethorphan have activating properties 1, 2

Monitoring Parameters

• Begin close monitoring within 1-2 weeks of the switch for worsening depression, suicidal ideation (especially in patients <24 years), agitation, or behavioral changes 6, 1
• Monitor blood pressure and heart rate at baseline and periodically during the first 12 weeks, as both bupropion and the combination can elevate these parameters 1, 2
• Assess for common adverse effects of Auvelity including dizziness, nausea, headache, somnolence, and anxiety 2

Alternative Conservative Approach (If Seizure Risk Factors Present)

If your patient has seizure risk factors or you prefer a more cautious approach:

• Taper standalone bupropion from 450 mg to 300 mg over 1-2 weeks 1, 4
• Then taper from 300 mg to 150 mg over another 1-2 weeks 1, 4
• Initiate Auvelity only after reaching 150 mg standalone bupropion 4
• Continue both for 1 week, then discontinue standalone bupropion 4
• This approach takes 3-5 weeks total but avoids exceeding 450 mg total daily bupropion at any point 1, 4

Contraindications to Verify Before Switching

• Confirm no current MAOI use or use within the past 14 days 1
• Verify no current opioid use if considering this switch (relevant for naltrexone-containing combinations, though not directly applicable to Auvelity) 1
• Confirm no uncontrolled hypertension, as Auvelity can further elevate blood pressure 1, 2
• Rule out seizure disorders, eating disorders, or conditions predisposing to seizures 1, 5

Expected Timeline for Clinical Effect

• Auvelity demonstrates rapid onset with improvement in depressive symptoms potentially within 1 week, faster than traditional antidepressants 3
• Full therapeutic effect should be assessed at 6-8 weeks 6, 1
• The dextromethorphan component provides NMDA receptor antagonism and sigma-1 receptor agonism, which may contribute to the rapid onset 3

Common Pitfalls to Avoid

• Do not abruptly discontinue the 450 mg bupropion when starting Auvelity, as this creates a sudden 240 mg reduction that may precipitate withdrawal symptoms or depressive relapse 4
• Do not forget to account for the bupropion content in Auvelity when calculating total daily bupropion exposure 1, 2
• Do not administer the second Auvelity dose late in the day, as this significantly increases insomnia risk 1
• Do not switch without verifying renal and hepatic function, as dose adjustments may be needed (reduce by 50% in moderate-severe renal impairment; maximum 150 mg daily in moderate-severe hepatic impairment) 1