Vilazodone
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Serotonin partial agonist reuptake inhibitor (SPARI)
Vilazodone
Viibryd
Vilazodone (brand name Viibryd) is a serotonin partial agonist reuptake inhibitor (SPARI) FDA-approved in 2011 for major depressive disorder. Combines SERT inhibition with 5HT1A receptor partial agonism — similar in spirit to buspirone-augmented SSRI therapy, but in a single molecule. Stahl positions SPARIs as a mechanistic refinement of SSRIs intended to accelerate the typical 4-6 week onset and improve tolerability via 5HT1A modulation.
In practice, head-to-head trials have not consistently shown superiority over generic SSRIs. The drug carries the typical SSRI side effect profile though sexual dysfunction may be somewhat reduced. Must be taken with food (substantial bioavailability difference).
SERT inhibition (Ki ~0.1 nM); 5HT1A partial agonist (Ki ~0.2 nM). Minimal NET, DAT, or non-5HT1A serotonin receptor activity.
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Effects
Nausea, diarrhea, headache, somnolence, insomnia, vomiting. Sexual dysfunction (variably reported as similar to or less than SSRIs). SSRI discontinuation syndrome possible. Class warning for suicidal thoughts in pediatric/young adult patients.
Pharmacodynamics
Interactions
Fluoxetine via Category:Antidepressants exp n/a/5 outcome n/a (n=1) exp 1.0/5 outcome +33.0 (n=1)
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Summary
Classes
Serotonin partial agonist reuptake inhibitor (SPARI)
Common uses
Major depressive disorder in adults (FDA-approved 2011)
Pharmacy
Starting dose
10 mg PO once daily × 7 days, then 20 mg × 7 days, then 40 mg as target dose (take with food)
Preparations
10 mg, 20 mg, 40 mg tablets
US FDA Max
40 mg/d
Pharmacology
Routes
Oral
Onset
4-6 weeks for full antidepressant effect (claimed earlier onset for some patients due to 5HT1A partial agonism)
Duration
Daily dosing
Half-life
~25 hours
Bioavailability
~72% (with food); much lower fasting (~36%)
Pregnancy
Limited data; weigh benefits/risks
Legal status
Rx
Purported mechanism
Combines SERT inhibition (typical SSRI mechanism) with 5HT1A receptor partial agonism. The 5HT1A partial agonism is proposed to: (1) provide intrinsic 5HT1A agonist activity beyond what SERT inhibition produces, and (2) accelerate downregulation of 5HT1A autoreceptors, potentially shortening the typical 4-6 week onset for SSRI effect.