Vilazodone Hydrochloride

Approved Indication (FDA):

• Major Depressive Disorder (MDD) in Adults:
  Vilazodone is approved for the treatment of major depressive disorder (MDD) in adults. It is used to alleviate symptoms such as persistent sadness, loss of interest, cognitive dysfunction, appetite disturbances, and suicidal ideation.

Clinically Accepted Off-label Uses:

• Generalized Anxiety Disorder (GAD):
  Clinical studies have suggested benefit in managing GAD symptoms due to vilazodone's anxiolytic properties.
• Obsessive-Compulsive Disorder (OCD):
  Occasionally used off-label in patients with OCD, especially in those who do not tolerate standard SSRIs well.
• Premenstrual Dysphoric Disorder (PMDD):
  May be used off-label in managing mood symptoms related to PMDD.

Note: Off-label use should follow professional judgment and guideline support.

Dosage Form: Oral tablets
Strengths Available in Bangladesh (per Medex): 10 mg, 20 mg, 40 mg

Adults (MDD):

• Initial Dose: 10 mg once daily for 7 days
• Titration: Increase to 20 mg once daily for 7 days, then to 40 mg once daily based on tolerability
• Maintenance Dose: 40 mg once daily
• Administration: Administer with food to ensure optimal absorption

Pediatrics:

• Not approved for individuals under 18 years of age

Elderly:

• No dosage adjustment needed, but monitor for heightened sensitivity to adverse effects

Renal Impairment:

• No dosage adjustment necessary

Hepatic Impairment:

• Use with caution in moderate to severe hepatic impairment due to insufficient data

Duration of Therapy:

• Initial evaluation after 6–8 weeks. Long-term maintenance may be required for recurrent depression.

Vilazodone is classified as a Serotonin Partial Agonist-Reuptake Inhibitor (SPARI). It combines two mechanisms: (1) inhibition of the serotonin transporter (SERT), leading to increased extracellular serotonin in the synaptic cleft, and (2) partial agonism at the 5-HT1A receptor, which modulates serotonin signaling. This dual action is believed to produce antidepressant effects and may result in a faster onset and reduced incidence of sexual side effects compared to traditional SSRIs.

• Absorption: Rapidly absorbed with peak plasma concentration (Tmax) at ~4–5 hours post-dose. Food significantly enhances absorption.
• Bioavailability: ~72% when taken with food
• Protein Binding: ~96–99%
• Volume of Distribution: ~7.5 L/kg
• Metabolism: Extensively metabolized in the liver, primarily via CYP3A4, with minor pathways through CYP2C19 and CYP2D6
• Half-life: ~25 hours
• Elimination: Primarily excreted in feces (~86%); <1% excreted in urine as unchanged drug

Pregnancy:

• FDA Pregnancy Risk Summary:
  Data from animal studies show potential embryofetal toxicity at high doses. Human data are limited. Use only if clearly needed and if benefits outweigh potential risks.

Lactation:

• Unknown whether vilazodone is excreted in human milk. Caution is advised when prescribing to lactating women due to potential infant exposure and adverse effects.

Consider maternal need and monitor infant for sedation, feeding issues, or developmental delays.

• Primary Class: Antidepressant
• Subclass:
• Selective Serotonin Reuptake Inhibitor (SSRI)
• 5-HT1A Partial Agonist
• Also referred to as SPARI (Serotonin Partial Agonist and Reuptake Inhibitor)

• Hypersensitivity to vilazodone or any of its excipients
• Use with monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuation of an MAOI
• Initiating MAOIs within 14 days of stopping vilazodone
• Concomitant use with linezolid or IV methylene blue

• Suicidality Risk:
  Antidepressants increase the risk of suicidal thoughts and behaviors in young adults under 25. Monitor closely, particularly during initiation and dose changes.
• Serotonin Syndrome:
  May occur, especially with concomitant serotonergic agents (e.g., SSRIs, SNRIs, triptans, tramadol).
• Seizure Risk:
  Use cautiously in patients with seizure disorders.
• Hyponatremia:
  Risk increased in elderly due to SIADH; monitor serum sodium.
• Bleeding Risk:
  Increased with concurrent use of NSAIDs, aspirin, or anticoagulants.
• Activation of Mania/Hypomania:
  Use cautiously in patients with bipolar disorder.
• Discontinuation Syndrome:
  Avoid abrupt withdrawal; taper gradually under supervision.

Common (≥5% incidence):

• Gastrointestinal: Diarrhea, nausea, vomiting
• CNS: Dizziness, insomnia, fatigue
• Psychiatric: Anxiety, restlessness
• Sexual: Decreased libido, delayed ejaculation

Serious/Severe:

• Suicidal ideation or behavior
• Seizures (rare)
• Serotonin syndrome
• Hyponatremia
• Bleeding episodes

Timing:

• Most side effects occur during the first few weeks and may be dose-dependent

Major Interactions:

• MAOIs, linezolid, methylene blue: Risk of serotonin syndrome – contraindicated
• CYP3A4 inhibitors (e.g., ketoconazole, ritonavir): May increase vilazodone levels – monitor or reduce dose
• CYP3A4 inducers (e.g., rifampin, carbamazepine): May reduce efficacy – avoid if possible
• Serotonergic drugs (e.g., SSRIs, SNRIs, triptans): Additive serotonergic effects
• NSAIDs, anticoagulants: Additive bleeding risk

Enzymatic Pathways:

• Primarily metabolized via CYP3A4
• Minor roles: CYP2C19, CYP2D6

• No recent changes in FDA labeling.
  Warnings on suicidality and serotonin syndrome remain unchanged.
• Clinical guidelines (e.g., APA, NICE):
  Vilazodone is not a first-line agent but may be considered in patients who do not tolerate traditional SSRIs, particularly those with sexual dysfunction.
• Recent studies:
  Suggest possible faster onset of action and reduced sexual side effects compared to SSRIs, although not conclusively superior in efficacy.

• Storage Temperature: 20°C to 25°C (68°F to 77°F)
• Permitted Excursion Range: 15°C to 30°C (59°F to 86°F)
• Humidity/Light Protection: Store in a dry place, protect from excessive moisture and light
• Handling: Keep in original container, tightly closed
• Reconstitution: Not applicable