Vilazodone (brand name Viibryd) is an antidepressant with a unique pharmacologic profile compared to most other agents in the SSRI class. While not a first-line choice for every patient, understanding its mechanism, adverse effects, and interaction profile is essential for optimizing therapy and preventing downstream prescribing problems.
Mechanism of ActionVilazodone is classified as a selective serotonin reuptake inhibitor (SSRI) and a partial agonist at the 5-HT1A receptor. The SSRI activity increases synaptic serotonin by blocking the serotonin transporter, while partial agonism at 5-HT1A receptors may contribute to antidepressant effects and potentially reduce certain SSRI-associated adverse effects (though clinical evidence for this benefit is mixed).
Adverse Effects
<ul class="wp-block-list">
<li>GI effects – diarrhea, nausea, and vomiting are frequent early in therapy. Taking the medication with food can help minimize these.</li>
<li>Insomnia – often dose-related; morning dosing may help.</li>
<li>Sexual dysfunction – may be slightly lower than with some SSRIs but still present.</li>
<li>Serotonin syndrome – rare but serious, particularly if combined with other serotonergic drugs.</li>
<li>Discontinuation syndrome – abrupt cessation can lead to dizziness, irritability, and flu-like symptoms.</li>
</ul>
Drug InteractionsVilazodone is primarily metabolized by CYP3A4. This means:
<ul class="wp-block-list">
<li>CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir) can increase vilazodone concentrations, potentially worsening side effects—dose reductions may be required.</li>
<li>CYP3A4 inducers (e.g., carbamazepine, rifampin, St. John’s Wort) can lower drug levels, reducing effectiveness.</li>
<li>Other serotonergic agents (e.g., triptans, SNRIs, MAOIs, tramadol, linezolid) increase the risk of serotonin syndrome.</li>
<li>Antiplatelets and anticoagulants – SSRIs can impair platelet aggregation, increasing bleeding risk when combined with aspirin, NSAIDs, or warfarin.</li>
</ul>
Prescribing Cascade ExamplesVilazodone’s adverse effects can easily lead to unnecessary prescriptions if side effects aren’t recognized:
<ol class="wp-block-list">
<li>GI upset → Acid suppression therapy – Diarrhea or nausea prompts the addition of proton pump inhibitors or antiemetics, instead of adjusting vilazodone dose or timing.</li>
<li>Insomnia → Hypnotic initiation – Trouble sleeping results in adding zolpidem or trazodone, without reassessing morning dosing or vilazodone’s role.</li>
<li>Sexual dysfunction → PDE5 inhibitor prescription – Erectile dysfunction leads to sildenafil use, when the root cause is vilazodone’s serotonergic activity.</li>
</ol>
Vilazodone’s combination of SSRI and 5-HT1A partial agonist activity makes it somewhat distinct, but its side effect profile and interactions require the same careful monitoring as other antidepressants. Healthcare professionals can play a key role in catching early signs of adverse effects, preventing prescribing cascades, and ensuring drug–drug interactions are managed appropriately.
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