Vortioxetine

MECHANISM OF ACTION

Vortioxetine works by blocking serotonin reuptake, boosting serotonin levels in the brain. It also affects various serotonin receptors, acting as a partial agonist at 5-HT1A (enhancing mood) and an antagonist at 5-HT3, 5-HT7, and 5-HT1D (reducing side effects). This combination helps relieve depressive symptoms and enhance cognitive function.

PHARMACOKINETICS

Absorption:

Vortioxetine is rapidly absorbed after oral intake, with peak levels reached in 7-11 hours. Its absorption is not significantly affected by food, so it can be taken with or without meals.

Distribution:

The drug is widely distributed throughout the body and is 98% bound to plasma proteins, indicating a high degree of protein binding.

Metabolism:

Vortioxetine is primarily metabolized in the liver by the CYP2D6 enzyme, producing inactive metabolites. Genetic variations in CYP2D6 can affect how individuals metabolize the drug, influencing its effectiveness and side effects.

Elimination:

The drug has a half-life of approximately 66 hours, which supports once-daily dosing. It is primarily eliminated through urine as metabolites. Steady-state plasma concentrations are generally achieved within 1 to 2 weeks of daily use.

DOSAGE AND ADMINISTRATION

For major depressive disorder (MDD) in adults, the typical starting dose of vortioxetine is 10 mg once daily, which can be increased to 20 mg if needed. The recommended dose is usually 10 mg daily. Elderly patients or those with liver impairment may start with 5 mg daily. Vortioxetine can be taken at any time of day, with or without food, and should be swallowed whole. When discontinuing, it’s best to gradually reduce the dose to avoid withdrawal symptoms.

DRUG INTERACTIONS

• Serotonergic drugs (e.g., SSRIs, SNRIs, triptans): Increased risk of serotonin syndrome.

• CYP2D6 inhibitors (e.g., fluoxetine, paroxetine): May raise vortioxetine levels, increasing side effects.

• CYP2D6 inducers (e.g., rifampin): May reduce vortioxetine's effectiveness.

• Alcohol: Can worsen side effects like dizziness or drowsiness.

• Anticoagulants/Antiplatelets: Increased risk of bleeding.

• Other antidepressants (e.g., MAO inhibitors): Risk of serotonin syndrome

CONTRAINDICATIONS

• Patients with a hypersensitivity to the drug.

• Those currently using monoamine oxidase inhibitors (MAOIs), due to the risk of serotonin syndrome.

• A 14-day washout period is required when switching from an MAOI to vortioxetine.

SIDE EFFECTS

Common side effects of vortioxetine (Trintellix) include:

• Nausea

• Diarrhea

• Dry mouth

• Dizziness

• Sexual issues (e.g., low libido, difficulty with orgasm)

• Constipation

• Fatigue

• Headaches

Serious side effects are rare but can include serotonin syndrome (e.g., agitation, hallucinations, high fever, and rapid heart rate), bleeding risks, and allergic reactions.

TOXICITY

Vortioxetine toxicity from overdose can cause nausea, vomiting, dizziness, seizures, drowsiness, and increased heart rate. Treatment is usually supportive, with activated charcoal if the overdose is recent. Seek emergency medical help immediately.