What is the potential interaction between Viibryd (vilazodone) and nortriptyline?

Potential Interaction Between Vilazodone (Viibryd) and Nortriptyline

The combination of vilazodone (Viibryd) and nortriptyline should be avoided due to the significant risk of serotonin syndrome, which can lead to potentially life-threatening complications. 1

Mechanism of Interaction

Vilazodone and nortriptyline interact through multiple mechanisms that increase serotonergic activity:

1. Pharmacodynamic interaction:

   • Vilazodone is both a selective serotonin reuptake inhibitor (SSRI) and a 5-HT1A receptor partial agonist 2, 3, 4
   • Nortriptyline is a tricyclic antidepressant (TCA) with serotonin reuptake inhibition properties 1
   • Combined use creates additive serotonergic effects that significantly increase risk of serotonin syndrome

2. Pharmacokinetic interaction:

   • Vilazodone may inhibit CYP2D6, which is involved in nortriptyline metabolism
   • This could lead to increased nortriptyline blood levels and enhanced toxicity

Clinical Risks

Serotonin Syndrome

The most serious risk is serotonin syndrome, characterized by:

• Mental status changes: confusion, agitation, anxiety
• Neuromuscular hyperactivity: tremors, clonus, hyperreflexia, muscle rigidity
• Autonomic hyperactivity: hypertension, tachycardia, arrhythmias, tachypnea, diaphoresis, shivering, vomiting, diarrhea
• Advanced symptoms: fever, seizures, arrhythmias, unconsciousness, which can lead to fatalities 1

Serotonin syndrome typically develops within 24-48 hours after combining serotonergic medications 1. Case reports have documented serotonin syndrome with vilazodone overdose 5, 6, highlighting its potent serotonergic effects.

Additional Risks

• Cardiac effects: Nortriptyline can cause cardiac conduction abnormalities, which may be exacerbated by the combination
• Anticholinergic effects: Nortriptyline's anticholinergic properties may be enhanced
• Sedation: Additive sedative effects may occur
• Seizure threshold reduction: Both medications can lower seizure threshold

Management Recommendations

If treatment with both agents is absolutely necessary (which is rarely the case):

1. Start with low doses of both medications and increase slowly
2. Monitor closely for symptoms of serotonin syndrome, especially during the first 24-48 hours after dosage changes
3. Educate patients about warning signs of serotonin syndrome
4. Consider alternative options:
   • For depression: Consider non-serotonergic antidepressants like bupropion 7
   • For neuropathic pain (if that's the indication for nortriptyline): Consider duloxetine or other SNRIs 1

Treatment of Serotonin Syndrome

If serotonin syndrome develops:

• Discontinue all serotonergic agents immediately
• Hospital-based supportive care with continuous cardiac monitoring
• Benzodiazepines for agitation and tremor
• Cyproheptadine (a serotonin antagonist) may be used in severe cases

Conclusion

Given the significant risk of serotonin syndrome and other potential adverse effects, the combination of vilazodone and nortriptyline should generally be avoided. Alternative treatment strategies that don't involve combining multiple serotonergic agents should be strongly considered to minimize risks to patient safety.