Viibryd
Viibryd
Generic Name
Viibryd
Mechanism
- Serotonin Reuptake Inhibition
- *Vilazodone* blocks the serotonin transporter (SERT), raising extracellular 5‑HT levels in the synaptic cleft, similar to conventional SSRIs.
- 5‑HT1A Partial Agonism
- As a *partial agonist* at the postsynaptic 5‑HT1A receptor, it enhances serotonergic tone while attenuating the paradoxical initial spike in serotonin that can cause anxiety or insomnia with traditional SSRIs.
- Clinical Benefit
- The dual action provides rapid antidepressant effects with potentially fewer anxiety‑related side effects.
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Pharmacokinetics
| Parameter | Detail |
| Absorption | Oral bioavailability ≈ 10 – 17 % (rapid rise to peak concentration in 1–2 h). |
| Food Effect | High‑fat meals delay absorption but do not reduce overall exposure. |
| Distribution | Volume of distribution ~ 5–6 L/kg; protein binding ~ 96 % (mostly albumin). |
| Metabolism | Primarily hepatic via CYP3A4 (≈ 90 % of exposure), minor CYP2D6 component. |
| Elimination | Half‑life ≈ 24 h (steady‑state reached in ~ 4 days). Renal clearance minimal; excretion mainly biliary. |
| Drug Interactions | Co‑administration with strong CYP3A4 inhibitors (e.g., ketoconazole) or inducers (e.g., carbamazepine) alters plasma concentrations. |
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Indications
- Major Depressive Disorder (MDD) in adults (≥ 18 years).
- Approved for monotherapy or for maintenance therapy in patients who have responded to acute treatment.
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Contraindications
| Category | Key Points |
| Contraindications | • Hypersensitivity to vilazodone or any excipient. |
| Warnings | • Serotonin Syndrome: Concurrent use with other serotonergic agents (MAOIs, triptans, tramadol, SSRIs, SNRIs). |
| • Suicidal Ideation/Critical Thinking: Must monitor for emergent suicidal thoughts, especially in patients ≤ 25 yrs or first 6 weeks. | |
| • Hyponatremia: Reduced risk vs SSRIs, but still possible. | |
| • Drug–Drug Interactions: Strong CYP3A4 inhibitors/inducers; care with CNS depressants. | |
| • Pregnancy: Animal data suggest potential fetal harm; use only if benefits outweigh risks. |
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Dosing
| Phase | Dose | Frequency | Notes |
| Initiation | 10 mg orally once daily | — | Start at 10 mg to allow dose titration. |
| Titration | 20 mg once daily | — | Increase to 20 mg after 1–2 weeks if tolerated. |
| Maintenance | 20 mg–40 mg once daily | — | Maximum recommended dose 40 mg; higher doses not justified by safety/efficacy data. |
| Escalation | 40 mg once daily | — | If necessary, 10 mg increments should be avoided; incremental dosing is not well studied. |
| Duration | 6–12 months for acute phase; ≥ 12 months for maintenance | — | Treatment should continue as long as benefit > risk. |
| Administration Tips | Take with food to reduce GI upset | — | No need for strict food timing; any meal is acceptable. |
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Adverse Effects
| Category | Examples |
| Common (≥ 10 %) | Nausea, diarrhea, insomnia, somnolence, somberness, hyponatremia (rare), generalized anxiety (initial). |
| Moderate (1–10 %) | Abdominal pain, changes in vision, weight change, dizziness, appetite change. |
| Serious (> 1 %) | Serotonin syndrome (characterized by hyperreflexia, agitation, hyperthermia), severe hyponatremia, acute GI bleeding, seizures in overdose, QT prolongation (rare). |
| Infusion/EMA | Rare (hypersensitivity reactions). |
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Monitoring
| Parameter | Frequency | Rationale |
| Liver Function Tests (ALT, AST, bilirubin) | Baseline, then 6 weeks, then every 3 months if abnormal | Antidepressants can elevate transaminases. |
| Serum Sodium | Baseline, 2–4 weeks, then every 3 months | Risk of hyponatremia. |
| Suicidal Ideation | Baseline, weekly during first 6 weeks, then monthly | FDA box warning. |
| Adherence & Dose Tolerance | Every visit | Detect early GI side effects. |
| Weight & BMI | Baseline, 6 weeks, then every 3 months | Avoid weight‑related complications. |
| QT Interval | Baseline (if risk factors), repeat if symptomatic | Minor QT risk. |
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Clinical Pearls
- Rapid Onset Advantage: The 5‑HT1A partial agonism may accelerate antidepressant response compared with traditional SSRIs, particularly in patients who experience anxiety or somnolence early in treatment.
- Lower Anxiety Profile: Due to partial agonism, initial anxiety or insomnia seen with other SSRIs is typically less pronounced—valuable for patients with comorbid anxiety disorders.
- Weight Neutrality: Unlike many SSRIs (e.g., paroxetine, sertraline), vilazodone shows no consistent weight gain or loss, making it suitable for patients concerned about metabolic side effects.
- CYP3A4 Medications: Because vilazodone is a CYP3A4 substrate, routine drugs such as statins or oral contraceptives may have altered levels; dose adjustments may be needed.
- Pregnancy Precaution: Although data are limited, some animal studies indicate potential teratogenicity; use only if the therapeutic benefit outweighs potential fetal risks.
- Drug–Drug Interaction Challenge: Because vilazodone’s activity relies on CNS serotonin levels, co‑administration with other serotonergic agents can be hazardous; discontinue MAOIs 14 days before starting vilazodone.
- Titration Should Be Slow: Aggressive dose escalation may increase nausea; a 2‑week interval between 10 mg and 20 mg is generally adequate.
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