Vilazodone (Viibryd)

Mechanism of action

• Blocks SERT, increasing synaptic serotonin, and simultaneously partially stimulates presynaptic 5-HT1A autoreceptors.
• The theoretical advantage: partial (rather than full) 5-HT1A agonism may desensitize these autoreceptors faster, reducing the initial negative-feedback dampening of serotonin release that normally delays SSRI onset - and the added post-synaptic 5-HT1A stimulation is thought to further boost net serotonergic tone. This was hypothesized to give a faster onset and fewer sexual side effects than plain SSRIs, though large trials have not shown consistent superiority over standard SSRIs (psychiatrist.com review; Psychopharmacology Institute).

Indication

• FDA-approved for Major Depressive Disorder (MDD) in adults. Not approved for pediatric use - safety/efficacy in children has not been established (Kaplan & Sadock's Synopsis of Psychiatry).
• Used off-label for generalized anxiety disorder, social anxiety, and OCD.

Dosing and administration

• Requires titration: typically started low and increased over about 2 weeks to the target dose to minimize GI side effects.
• Must be taken with food. Without food, absorption is markedly reduced and effectiveness may be diminished (Kaplan & Sadock's Synopsis of Psychiatry).

Pharmacokinetics / drug interactions

• Metabolized primarily by CYP3A4.
• Strong CYP3A4 inhibitors (e.g., ketoconazole, grapefruit juice) can raise vilazodone plasma levels by 50% or more, requiring dose reduction; CYP3A4 inducers can lower levels (Katzung's Basic and Clinical Pharmacology; Kaplan & Sadock's Comprehensive Textbook of Psychiatry).
• Vilazodone itself is neither a potent inhibitor nor strong inducer of CYP enzymes.

Adverse effects

• Diarrhea (~28% vs 9% placebo in phase III trials)
• Nausea (~23% vs 5% placebo)
• Dizziness, insomnia, vomiting, abnormal dreams, akathisia/restlessness, palpitations, tremor, feeling jittery

Safety signals / precautions

• Like other serotonergic antidepressants, carries a risk of serotonin syndrome when combined with other serotonergic agents (MAOIs, SSRIs, SNRIs, triptans, tramadol, buspirone, tryptophan) - contraindicated with MAOIs or within 14 days of MAOI use.
• In vitro, vilazodone was clastogenic in some mammalian cell assays though not mutagenic in bacterial reverse mutation testing (per package insert data cited in Kaplan & Sadock's).
• Standard antidepressant class warnings apply (suicidality risk in young adults, discontinuation syndrome if stopped abruptly - see Maudsley Deprescribing Guidelines for tapering advice).

Vilazodone's dual action at SERT and 5-HT1A receptors (Stahl's Essential Psychopharmacology).

Evidence check