Can You Take Auvelity and Vibryd Together?
No, you should not take Auvelity (dextromethorphan/bupropion) together with Vibryd (vilazodone) without extreme caution and close monitoring, because this combination significantly increases the risk of serotonin syndrome—a potentially life-threatening condition.
Critical Safety Concern: Serotonin Syndrome Risk
The primary danger of combining Auvelity with Vibryd is serotonin syndrome. While bupropion itself has minimal direct serotonergic activity, dextromethorphan (the other component of Auvelity) is a known serotonergic agent. 1 When combined with Vibryd—a serotonin reuptake inhibitor and 5-HT1A partial agonist—the cumulative serotonergic load can trigger this medical emergency. 1
Signs of Serotonin Syndrome to Monitor
If this combination is used, watch for the following symptoms, which typically emerge within 24–48 hours of initiation or dose escalation: 2
- Mental status changes: confusion, agitation, restlessness 2
- Neuromuscular hyperactivity: tremor, muscle rigidity, clonus (rhythmic muscle jerking), hyperreflexia 2
- Autonomic instability: elevated blood pressure, rapid heart rate, profuse sweating, fever 2
FDA Drug Label Warnings for Auvelity
The FDA-approved labeling for bupropion (a component of Auvelity) explicitly cautions about combining it with other serotonergic drugs. 3 Although the label does not specifically name vilazodone, the warning applies to all serotonergic antidepressants, including SSRIs, SNRIs, and serotonin modulators like Vibryd. 3
Key FDA Contraindications and Precautions
- Seizure risk: Auvelity contains bupropion, which lowers the seizure threshold. The risk is dose-dependent and increases when combined with other medications that also lower seizure threshold. 3, 4
- Maximum bupropion dose: Do not exceed 450 mg/day of total bupropion (from all sources combined) to maintain seizure risk at approximately 0.1%. 2
- MAOI interaction: At least 14 days must elapse between discontinuing an MAOI and starting Auvelity, or vice versa, due to hypertensive crisis risk. 3
Clinical Evidence on Auvelity
Auvelity is a fixed-dose combination of dextromethorphan 45 mg and bupropion 105 mg per tablet, approved for major depressive disorder in adults. 4, 5 The bupropion component serves two roles: it inhibits CYP2D6 to increase dextromethorphan bioavailability, and it provides additional antidepressant effects through dopamine and norepinephrine reuptake inhibition. 6, 7
Efficacy and Onset
- Phase 2 and 3 trials demonstrated significant reductions in depression scores within 1–2 weeks, faster than traditional antidepressants. 6, 7
- Remission rates approached 70% in long-term open-label studies, with response rates exceeding 80%. 6
Common Adverse Effects
The most frequent side effects of Auvelity include dizziness, nausea, headache, diarrhea, somnolence, dry mouth, sexual dysfunction, hyperhidrosis, anxiety, constipation, decreased appetite, and insomnia. 4
Real-World Use Patterns
A 2024 analysis of 22,288 patients initiating Auvelity in the U.S. found that: 8
- 71.2% added Auvelity to existing antidepressants (most commonly SSRIs or SNRIs), while 28.8% used it as monotherapy. 8
- 10.1% were treatment-naïve at initiation. 8
- The majority had previously tried SSRIs (54.9%), bupropion (40.4%), or SNRIs (35.9%). 8
This real-world data confirms that combination therapy with Auvelity is common in clinical practice, but it does not address the specific safety of combining it with vilazodone (Vibryd).
Practical Management Algorithm
Step 1: Assess Absolute Contraindications
Before considering this combination, verify the patient does not have: 2, 3
- History of seizures or conditions predisposing to seizures (brain tumor, stroke, head trauma, eating disorders)
- Current or recent MAOI use (within 14 days)
- Uncontrolled hypertension
- Moderate-to-severe hepatic or renal impairment
Step 2: Calculate Total Bupropion Exposure
- Each Auvelity tablet contains 105 mg bupropion. 4
- Standard Auvelity dosing is one tablet twice daily (total 210 mg bupropion/day). 4
- Do not exceed 450 mg/day total bupropion from all sources. 2, 3
Step 3: Initiate with Extreme Caution
If the combination is deemed necessary after weighing risks and benefits:
- Start with the lowest effective dose of Auvelity (one tablet daily in the morning). 2
- Monitor intensively during the first 24–48 hours for serotonin syndrome symptoms. 2
- Educate the patient to seek immediate medical attention if they develop confusion, muscle rigidity, fever, or rapid heart rate. 2
Step 4: Ongoing Monitoring
- Blood pressure and heart rate: Check at baseline and periodically during the first 12 weeks, as bupropion can elevate both. 2, 9
- Suicidal ideation: Assess weekly during the first month, especially in patients under 24 years old, due to the FDA black-box warning for all antidepressants. 2, 4
- Seizure risk factors: Avoid alcohol, ensure adequate sleep, and counsel against abrupt discontinuation of benzodiazepines or other CNS depressants. 3
Alternative Strategies
If Vibryd Is Ineffective Alone
Rather than adding Auvelity to Vibryd, consider these evidence-based alternatives:
- Switch to Auvelity monotherapy: Discontinue Vibryd and initiate Auvelity alone after an appropriate washout period (typically 5 half-lives of vilazodone, approximately 5–7 days). 2
- Augment Vibryd with bupropion monotherapy (not Auvelity): This avoids the additional serotonergic load from dextromethorphan while still providing dopaminergic/noradrenergic augmentation. 2
If Auvelity Is Ineffective Alone
- Add an SSRI or SNRI (not Vibryd): Low-quality evidence supports augmenting bupropion with SSRIs like sertraline or escitalopram, which have more established safety profiles in combination. 2
Common Pitfalls to Avoid
- Underestimating serotonin syndrome risk: Even though bupropion alone has minimal serotonergic activity, dextromethorphan is a potent serotonin modulator. 1
- Exceeding maximum bupropion dose: Always account for bupropion from all sources (Auvelity, standalone bupropion, naltrexone-bupropion). 2, 3
- Skipping early monitoring: The highest risk for serotonin syndrome and suicidal ideation occurs in the first 1–2 weeks. 2, 4
- Ignoring cardiovascular effects: Bupropion can raise blood pressure and heart rate, particularly in patients with pre-existing hypertension. 2, 9
Bottom Line
The combination of Auvelity and Vibryd carries significant risk of serotonin syndrome and should generally be avoided. If clinical circumstances require this combination, initiate with the lowest dose, monitor intensively for the first 48 hours, and educate the patient about warning signs. In most cases, switching to Auvelity monotherapy or augmenting Vibryd with bupropion alone (rather than the dextromethorphan-bupropion combination) is a safer approach. 1, 2, 3, 4