How should I taper carbamazepine (Tegretol) before initiating Auvelity (dextromethorphan‑bupropion) for mood treatment?

Carbamazepine Tapering Before Auvelity Initiation

You must taper carbamazepine completely off before starting Auvelity, because carbamazepine induces bupropion metabolism so dramatically that it reduces bupropion levels by 87-90%, rendering Auvelity therapeutically ineffective. 1

Critical Drug Interaction

Carbamazepine is a potent enzyme inducer that destroys bupropion's therapeutic effect:

• Carbamazepine decreases bupropion peak concentrations by 87% and 24-hour area under the curve by 90% 1
• This interaction reduces bupropion to non-detectable plasma levels in some patients 2
• Carbamazepine simultaneously increases hydroxybupropion (the metabolite) by 71-94%, but this does not compensate for the loss of parent drug 1
• This interaction makes Auvelity (which contains bupropion) essentially useless while on carbamazepine 1, 2

Recommended Carbamazepine Tapering Protocol

Taper carbamazepine gradually over 1-2 weeks minimum:

• Reduce the dose by 25% of the current dose every 3-7 days 3
• For example, if on 800 mg/day: reduce to 600 mg/day for 3-7 days, then to 400 mg/day for 3-7 days, then to 200 mg/day for 3-7 days, then discontinue 3
• Never stop carbamazepine abruptly, as this can precipitate seizures if the patient has epilepsy 3
• Monitor for return of original symptoms (seizures if used for epilepsy, mood instability if used for mood stabilization) 3

Timing of Auvelity Initiation

Wait at least 5-7 days after the last carbamazepine dose before starting Auvelity:

• Carbamazepine has a half-life requiring several days for enzyme induction effects to reverse 1
• Starting Auvelity too soon means the residual enzyme induction will still reduce bupropion levels 1
• A 5-7 day washout period allows hepatic enzyme activity to normalize 1

Auvelity Dosing After Carbamazepine Discontinuation

Follow standard Auvelity titration once carbamazepine is fully cleared:

• Week 1: 1 tablet (45 mg dextromethorphan/105 mg bupropion) once daily in the morning 4
• Week 2: 1 tablet twice daily (morning and afternoon, not late in day to avoid insomnia) 5, 4
• Do not take the second dose late in the day to minimize insomnia risk 5

Monitoring During Transition

Watch for these specific issues during the carbamazepine taper and Auvelity initiation:

• Seizure risk: If carbamazepine was prescribed for epilepsy, coordinate with neurology before tapering 3
• Mood destabilization: If carbamazepine was used for mood stabilization, monitor closely for manic or depressive symptoms during the taper 2
• Auvelity side effects: Dizziness, nausea, headache, insomnia, anxiety, and seizures (especially at higher doses) are the most common adverse effects 4
• Seizure threshold: Bupropion (in Auvelity) lowers seizure threshold; avoid in patients with seizure disorders or factors that increase seizure risk 5

Critical Safety Warnings for Auvelity

Auvelity carries specific contraindications and warnings:

• Seizure risk: More likely at higher doses; contraindicated in patients with seizure disorders 5, 4
• Suicidal ideation: Black box warning for increased risk of suicidal thoughts in pediatric and young adult patients 4
• MAOI interaction: Avoid within 14 days of MAOI use 5
• Neuropsychiatric effects: Monitor for depression, suicidal thoughts, hostility, especially in patients under 24 years 5

Common Pitfalls to Avoid

• Do not start Auvelity while still on carbamazepine – the drug interaction makes it ineffective 1, 2
• Do not rush the carbamazepine taper – abrupt discontinuation risks seizures 3
• Do not skip the washout period – residual enzyme induction will persist for days 1
• Do not dose Auvelity late in the day – the second dose should be in the afternoon to avoid insomnia 5
• Do not use in patients with uncontrolled seizure disorders – bupropion lowers seizure threshold 5