Safety of Starting Wellbutrin and Buspar Together
Yes, it is safe to start Wellbutrin (bupropion) and Buspar (buspirone) together—this combination is commonly used in clinical practice and is explicitly recommended by the American Academy of Family Physicians for conditions like treatment-resistant depression. 1
Evidence Supporting Combined Use
The combination of bupropion and buspirone has been studied specifically in patients with depression who failed initial antidepressant therapy:
In the STAR*D trial, augmenting an SSRI with either bupropion or buspirone showed similar remission rates (29.7% vs 30.1% respectively), demonstrating that both agents are effective and safe augmentation strategies. 2
No significant safety concerns emerged when these medications were combined in controlled trials, with both showing comparable tolerability profiles. 2
Clinical experience from uncontrolled series demonstrates that combining bupropion with other antidepressants (including buspirone) appears safe with conservative dosing and close monitoring, with no seizures reported in 27 patients followed for a mean of 11 months. 3
Key Safety Considerations
Seizure Risk (Primary Concern)
- Bupropion lowers the seizure threshold and requires dose limitation to 300 mg per day maximum to minimize this risk. 1
- Buspirone does not significantly increase seizure risk, so this concern relates primarily to bupropion alone. 1
- Avoid this combination in patients with active seizure disorders, brain metastases, or conditions that lower seizure threshold. 1
Cardiovascular Monitoring
- Both medications can affect heart rate and blood pressure, requiring baseline and periodic vital sign monitoring, particularly in patients with cardiovascular disease or hypertension. 1
Dystonia Risk (Rare but Documented)
- One case report documented acute dystonia (neck stiffness, trismus, TMJ pain) when bupropion was combined with buspirone, though symptoms resolved with dose reduction and did not recur with buspirone alone. 4
- This appears to be a rare, dose-related phenomenon that may involve dopaminergic and serotonergic system interactions. 4
Recommended Dosing Strategy
Start bupropion at 150 mg once daily, increase to 150 mg twice daily after 3-7 days if tolerated, with a maximum of 300 mg/day. 1
For buspirone, typical augmentation dosing reaches up to 60 mg per day in divided doses. 2
Absolute Contraindications
Do not use this combination in patients with:
- Active seizure disorder or conditions lowering seizure threshold 1
- Uncontrolled hypertension 1
- Concurrent MAO inhibitor use 1
- Pregnancy or active attempts to conceive 1
Required Monitoring
- Baseline and periodic vital signs (blood pressure, heart rate) 1
- Signs of serotonin syndrome 1
- Neuropsychiatric effects including suicidal ideation 1
- Seizure activity, particularly with dose escalation 1
- Dystonic reactions (neck stiffness, jaw tightness) 4
Common Pitfalls to Avoid
Do not exceed 300 mg/day of bupropion when combining with other medications, as seizure risk increases significantly at higher doses. 1
Watch for dose-related dystonic reactions if patients develop neck stiffness or jaw symptoms within 24-48 hours of dose increases—reduce bupropion dose immediately if this occurs. 4