What is the recommended protocol to taper off Sobril (Clonazepam) and introduce Wellbutrin (Bupropion) for a patient taking 15 mg of Sobril three times a day, switching to 150 mg of Wellbutrin per day for one week and then 300 mg per day?

Tapering Sobril and Initiating Wellbutrin

Critical Safety Issue: Sobril Dosing Error

The stated dose of "Sobril 15 mg x 3" appears to be an error, as Sobril (oxazepam) is not typically available in 15 mg formulations and standard dosing does not reach 45 mg/day for most indications. Assuming this refers to a benzodiazepine at therapeutic doses, the following protocol applies, but the actual current dose must be verified before proceeding.

Recommended Transition Protocol

Do not abruptly discontinue the benzodiazepine while starting Wellbutrin—taper the benzodiazepine gradually over 4-8 weeks using 25% dose reductions every 1-2 weeks, while initiating Wellbutrin at 150 mg daily for 4-7 days before increasing to 300 mg daily. 1, 2

Step 1: Initiate Wellbutrin First

• Start Wellbutrin XL 150 mg once daily in the morning (taken with or without food, swallowed whole) 2
• Continue this dose for 4-7 days minimum before increasing 2
• After the initial period, increase to 300 mg once daily if tolerated 2
• Monitor for seizure risk, especially given concurrent benzodiazepine use 2

Step 2: Begin Benzodiazepine Taper (After Wellbutrin is Stable)

Wait until Wellbutrin has been at therapeutic dose (300 mg) for at least 1-2 weeks before beginning the benzodiazepine taper, as starting the taper too early may destabilize mood and increase anxiety. 1

Benzodiazepine tapering schedule:

• Reduce dose by 25% every 1-2 weeks 1
• Monitor for withdrawal symptoms (rebound anxiety, insomnia, tremor, rarely seizures) after each reduction 1
• If withdrawal symptoms emerge, return to the previous well-tolerated dose and slow the taper 3
• Total taper duration: typically 4-8 weeks depending on tolerance 1

Step 3: Monitoring During Transition

Critical monitoring points:

• Seizure risk is elevated with Wellbutrin, particularly at doses >300 mg/day or with rapid dose escalation 2
• Neuropsychiatric symptoms: Monitor for worsening depression, suicidal ideation, hostility, or agitation during both Wellbutrin initiation and benzodiazepine withdrawal 1, 2
• Benzodiazepine withdrawal symptoms: anxiety, insomnia, tremor, hallucinations, seizures (rare but serious) 1
• Wellbutrin side effects: insomnia, nervousness, nausea (common); myoclonus (rare, dose-related) 4, 5

Key Safety Considerations

Why Taper Benzodiazepines Gradually

Abrupt benzodiazepine discontinuation can cause seizures, delirium tremens, and death in rare cases, making gradual tapering essential. 1 The CDC guideline specifically notes that when patients are on both opioids and benzodiazepines, it may be safer to taper opioids first due to greater risks of benzodiazepine withdrawal—this same caution applies when transitioning to Wellbutrin. 1

Wellbutrin Dosing Limits

• Maximum dose: 450 mg/day 2
• Do not exceed 300 mg/day initially—doses >450 mg/day are associated with increased seizure risk and may trigger mania in susceptible individuals 2, 6
• The planned dose of 300 mg daily is appropriate and within FDA-approved limits 2

Drug Interaction Concerns

Wellbutrin lowers seizure threshold, and concurrent benzodiazepine withdrawal (which can also cause seizures) creates additive risk during the transition period. 2 This reinforces the need to:

1. Stabilize Wellbutrin first
2. Taper benzodiazepine slowly
3. Never abruptly stop the benzodiazepine

Common Pitfalls to Avoid

• Tapering benzodiazepine too quickly: Use the 25% every 1-2 weeks schedule, not faster 1
• Starting benzodiazepine taper before Wellbutrin is stable: Wait 1-2 weeks after reaching Wellbutrin 300 mg 1, 2
• Crushing or splitting Wellbutrin XL tablets: Must be swallowed whole 2
• Ignoring withdrawal symptoms: If anxiety or other withdrawal symptoms emerge, slow or pause the taper 1
• Exceeding 300 mg Wellbutrin without clear indication: Higher doses increase seizure and mania risk 2, 6

Alternative Approach if Anxiety Worsens

If anxiety significantly worsens during benzodiazepine taper despite stable Wellbutrin therapy, consider evidence-based psychotherapy (CBT) or non-benzodiazepine anxiolytics rather than reversing the taper. 1 CBT specifically increases benzodiazepine tapering success rates. 1