Vortioxetine

• Major Depressive Disorder
• Depression with Cognitive Symptoms
• Mood Disorders

Vortioxetine is a multimodal antidepressant that combines serotonin reuptake inhibition with direct modulation of multiple serotonin receptors. It is used to treat major depressive disorder and may have benefits for cognitive symptoms of depression.

Mechanism of Action

Vortioxetine has a complex, multimodal mechanism:

• Serotonin reuptake inhibition: Blocks SERT
• 5-HT3 receptor antagonism: May reduce nausea and improve mood
• 5-HT7 receptor antagonism: May enhance cognition and mood
• 5-HT1D receptor antagonism: May enhance serotonin release
• 5-HT1B receptor partial agonism: Modulates serotonin release
• 5-HT1A receptor agonism: Anxiolytic and antidepressant effects

This multimodal profile may provide cognitive and emotional benefits beyond traditional SSRIs.

Available Formulations

Vortioxetine is available as tablets:

• 5 mg, 10 mg, 20 mg tablets (Trintellix)

Medical Uses

FDA-Approved Indication:

• Major depressive disorder in adults

May be particularly useful for patients with cognitive symptoms of depression.

Dosing Guidelines

Adults:

• Starting dose: 10 mg once daily
• Range: 5-20 mg once daily
• May increase to 20 mg based on response and tolerability
• May reduce to 5 mg if 10 mg not tolerated

CYP2D6 Poor Metabolizers:

• Maximum: 10 mg once daily

With Strong CYP2D6 Inhibitors:

• Reduce vortioxetine dose by half

With Strong CYP Inducers:

• Consider increasing dose (max 3x original dose)

Discontinuation:

• May taper to 10 mg for one week before stopping if on 15-20 mg

Important Safety Information

Black Box Warning:

• Increased risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders

Contraindications:

• Concomitant use with MAOIs or within 21 days of stopping MAOI (or 14 days after stopping vortioxetine before starting MAOI)

Warnings and Precautions:

• Serotonin syndrome: Risk with other serotonergic drugs
• Abnormal bleeding: May increase bleeding risk
• Activation of mania/hypomania: Use with caution in bipolar disorder
• Hyponatremia: SIADH reported, especially in elderly
• Angle-closure glaucoma: May trigger in susceptible individuals

Drug Interactions

• MAOIs: Contraindicated
• Strong CYP2D6 inhibitors (bupropion, fluoxetine, paroxetine, quinidine): Reduce vortioxetine dose by half
• Strong CYP inducers (rifampin, carbamazepine, phenytoin): Consider increasing dose
• Serotonergic drugs: Increased serotonin syndrome risk
• NSAIDs, aspirin, anticoagulants: Increased bleeding risk

Special Populations

• Hepatic Impairment: No adjustment needed for mild to moderate; not studied in severe
• Renal Impairment: No adjustment needed
• CYP2D6 Poor Metabolizers: Maximum 10 mg daily
• Elderly: No routine adjustment; consider slower titration
• Pregnancy: May cause neonatal complications; use only if benefit outweighs risk
• Lactation: Present in milk; consider risk vs benefit
• Pediatric: Safety and efficacy not established