Introduction
Vilazodone (marketed as Viibryd®) is an antidepressant medication approved by the U.S. Food and Drug Administration (FDA) in 2011. It represents a unique pharmacological class as a serotonin partial agonist and reuptake inhibitor (SPARI), combining two distinct mechanisms of action in a single molecule. Vilazodone is indicated for the treatment of major depressive disorder (MDD) in adults.
Mechanism of Action
Vilazodone exerts its therapeutic effects through a dual mechanism: 1. Serotonin Reuptake Inhibition: It acts as a potent selective serotonin reuptake inhibitor (SSRI), blocking the serotonin transporter (SERT), which increases synaptic concentrations of serotonin in the brain. 2. 5-HT1A Receptor Partial Agonism: It acts as a partial agonist at serotonin 5-HT1A receptors. This activity is thought to enhance serotonin transmission while potentially mitigating some side effects associated with pure SSRIs, such as sexual dysfunction and initial anxiety.
This combination may provide a more rapid onset of antidepressant action and improved tolerability profile compared to conventional SSRIs.
Indications
- FDA-approved: Treatment of major depressive disorder (MDD) in adults
Dosage and Administration
- Initial dose: 10 mg orally once daily for 7 days
- Dose titration: Increase to 20 mg once daily for an additional 7 days
- Maintenance dose: 40 mg once daily
- Administration: Must be taken with food to ensure adequate absorption
- Special populations:
- Renal impairment: No dosage adjustment necessary for mild to moderate impairment. Use with caution in severe renal impairment. - Hepatic impairment: No dosage adjustment necessary for mild impairment. Maximum recommended dose is 20 mg daily in moderate to severe impairment. - Geriatric patients: Use caution; consider lower doses due to potential increased sensitivity - Pediatric patients: Safety and effectiveness not established
Pharmacokinetics
- Absorption: Bioavailability is 72% when administered with food. Tmax is 4-5 hours post-dose.
- Distribution: Mean apparent volume of distribution is approximately 22 L. Protein binding is 96-99%, primarily to albumin and α1-acid glycoprotein.
- Metabolism: Extensive hepatic metabolism primarily via CYP3A4, with minor contributions from CYP2C19 and CYP2D6. The major metabolite, M10 and M17, are inactive.
- Elimination: Half-life is approximately 25 hours. Excretion is primarily fecal (≈90%) with minor renal elimination (≈2%).
Contraindications
- Concomitant use with monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuing MAOI therapy
- Known hypersensitivity to vilazodone or any component of the formulation
Warnings and Precautions
- Suicidal thoughts and behaviors: Monitor for emergence or worsening of depression, suicidal thoughts, or unusual changes in behavior, particularly during initial treatment and dose adjustments
- Serotonin syndrome: Risk especially with concomitant serotonergic drugs
- Activation of mania/hypomania: Screen patients for bipolar disorder
- Discontinuation syndrome: Taper gradually when discontinuing treatment
- Abnormal bleeding: May increase risk of bleeding events
- Angle-closure glaucoma: May precipitate attacks in anatomically susceptible patients
- Hyponatremia: May occur due to SIADH, particularly in elderly patients and those taking diuretics
Drug Interactions
- MAOIs: Contraindicated due to risk of serotonin syndrome
- Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin): May increase vilazodone concentrations; consider dose reduction
- Strong CYP3A4 inducers (e.g., rifampin, carbamazepine): May decrease vilazodone concentrations; consider dose adjustment
- Other serotonergic drugs (e.g., tramadol, triptans, other antidepressants): Increased risk of serotonin syndrome
- Drugs that prolong QTc interval: Use with caution
- NSAIDs, aspirin, warfarin: Increased risk of bleeding
- Alcohol: May enhance cognitive and motor effects
Adverse Effects
- Common (≥5% and twice placebo):
- Diarrhea (28% vs 9%) - Nausea (23% vs 5%) - Insomnia (6% vs 2%) - Vomiting (5% vs 1%)
- Serious:
- Suicidal ideation and behaviors - Serotonin syndrome - Mania/hypomania - Seizures - Hyponatremia - Abnormal bleeding
Monitoring Parameters
- Mental status: Mood changes, suicidal ideation, emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity
- Clinical response: Depression rating scales (e.g., PHQ-9)
- Adverse effects: GI symptoms, sexual dysfunction, weight changes
- Laboratory: Electrolytes (particularly in elderly and those on diuretics), liver function tests
- Therapeutic drug monitoring: Not routinely indicated
Patient Education
- Take with food to ensure proper absorption
- Do not abruptly discontinue medication; work with prescriber to taper dose
- Report any worsening depression, suicidal thoughts, or unusual behavior changes immediately
- Be aware of potential side effects including nausea, diarrhea, and insomnia
- Avoid alcohol consumption during treatment
- Inform all healthcare providers about vilazodone use, particularly before starting new medications
- Use caution when operating machinery until effects are known
- Report any signs of bleeding or bruising easily
- Notify prescriber if pregnancy is planned or suspected
References
1. FDA prescribing information for Viibryd (vilazodone hydrochloride). Revised 2021. 2. Citrome L. Vilazodone for major depressive disorder: a systematic review of the efficacy and safety profile for this newly approved antidepressant. Int J Clin Pract. 2011;65(12):1229-1239. 3. Khan A, Cutler AJ, Kajdasz DK, et al. A randomized, double-blind, placebo-controlled, 8-week study of vilazodone, a serotonergic agent for the treatment of major depressive disorder. J Clin Psychiatry. 2011;72(4):441-447. 4. Rickels K, Athanasiou M, Robinson DS, et al. Evidence for efficacy and tolerability of vilazodone in the treatment of major depressive disorder: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2009;70(3):326-333. 5. Stahl SM. Mechanism of action of vilazodone: a novel antidepressant for the treatment of major depressive disorder. CNS Spectr. 2011;16(5):93-97. 6. Schwartz TL, Siddiqui UA, Stahl SM. Vilazodone: a brief pharmacological and clinical review of the novel serotonin partial agonist and reuptake inhibitor. Ther Adv Psychopharmacol. 2011;1(3):81-87.