Vortioxetine is indicated for the treatment of major depressive disorder (MDD) in adults.

The exact mechanism behind the antidepressant effect of Vortioxetine is not fully understood. However, it is believed to enhance serotonergic activity within the central nervous system through inhibition of serotonin (5-HT) reuptake. Vortioxetine also exhibits multiple receptor activities, including 5-HT3 receptor antagonism and 5-HT1A receptor agonism.

Recommended dose: The recommended starting dose is 10 mg administered orally once daily without regard to meals. The dosage should then be increased to 20 mg/day, as tolerated. The efficacy and safety of doses above 20 mg/day have not been evaluated in controlled clinical trials. A dose decrease down to 5 mg/day may be considered for patients who do not tolerate higher doses. The lowest effective dose of 5 mg/day should always be used as the starting dose for elderly patients (>65 years of age).

Maintenance dose: For MDD, Vortioxetine can be administered for several months or longer. For a long period use patients should be re-evaluated to assess the usefulness of the drugs for individual patients.

Discontinuation treatment: Although Vortioxetine can be abruptly discontinued, in placebo-controlled trials patients experienced transient adverse reactions such as headache and muscle tension following abrupt discontinuation of Vortioxetine 15 mg/day or 20 mg/day. To avoid these adverse reactions, it is recommended that the dose should be decreased to 10 mg/day for one week before full discontinuation of Vortioxetine 15 mg/day or 20 mg/day.

Switching a patient to or from a Monoamine Oxidase Inhibitor (MAOI) intended to treat Psychiatric Disorders: At least 14 days must elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with Vortioxetine to avoid the risk of Serotonin Syndrome. Conversely, at least 21 days must elapse after stopping Vortioxetine before starting an MAOI intended to treat psychiatric disorders.

Monoamine Oxidase Inhibitors: Serious and potentially fatal adverse reactions may occur in patients using MAOIs, or in those who have recently discontinued an MAOI and started serotonergic antidepressants, or recently stopped SSRI or SNRI therapy before initiating an MAOI.

Serotonergic drugs: Concomitant use of Vortioxetine with other medications affecting serotonergic neurotransmitter systems (such as SSRIs, SNRIs, triptans, buspirone, tramadol, and tryptophan-containing products) may increase the risk of serotonin toxicity or serotonin syndrome. Patients should be closely monitored for symptoms of serotonin syndrome, and treatment should be discontinued immediately if it occurs.

Other CNS active agents: No clinically significant effects were observed on steady-state lithium exposure following co-administration with repeated doses of Vortioxetine.

Potential for other drugs to affect Vortioxetine: Reduce the dose of Vortioxetine by half when administered with strong CYP2D6 inhibitors (e.g. bupropion, fluoxetine, paroxetine, quinidine). Consider increasing the Vortioxetine dose when co-administered with strong CYP inducers such as rifampin, carbamazepine, or phenytoin.

Vortioxetine Hydrobromide is contraindicated in patients with known hypersensitivity to Vortioxetine or any excipient of this formulation, and in patients receiving concomitant Monoamine Oxidase Inhibitors (MAOIs).

Patients receiving Vortioxetine may experience adverse reactions such as hypersensitivity, worsening depression or suicidal thoughts, serotonin syndrome, abnormal bleeding, activation of mania or hypomania, angle-closure glaucoma, and hyponatremia.

The safety of Vortioxetine during human pregnancy has not been established. Therefore, it should not be used during pregnancy or in women planning pregnancy unless the expected benefits clearly outweigh the potential risks to the fetus. Animal studies have demonstrated excretion of Vortioxetine metabolites into milk. Since risk to the nursing infant cannot be excluded, breastfeeding is not recommended during treatment with Vortioxetine.

Clinical Worsening and Suicide Risk: All patients receiving antidepressant therapy for any indication should be monitored carefully for clinical worsening, suicidal thoughts or behavior, and unusual behavioral changes, especially during the first few months of treatment or during dosage adjustments.

Serotonin Syndrome: Potentially life-threatening serotonin syndrome has been reported with serotonergic antidepressants including Vortioxetine, particularly when used together with other serotonergic agents such as triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John’s Wort, and drugs that impair serotonin metabolism, including MAOIs, linezolid, and intravenous methylene blue.

Abnormal Bleeding: Drugs that interfere with serotonin reuptake inhibition, including Vortioxetine, may increase the risk of bleeding. Concomitant use of aspirin, NSAIDs, warfarin, or other anticoagulants may further increase this risk.

Mania/Hypomania: As with other antidepressants, Vortioxetine should be used cautiously in patients with a history or family history of bipolar disorder, mania, or hypomania.

Angle Closure Glaucoma: Pupillary dilation associated with antidepressants including Vortioxetine may precipitate an angle-closure attack in susceptible patients with anatomically narrow angles who do not have a patent iridectomy.

Hyponatremia: Hyponatremia has been reported during treatment with serotonergic medications.

Pediatric use (<18 years of age): The safety and effectiveness of Vortioxetine in pediatric patients have not been established.

Geriatric use (>65 years of age): No dosage adjustment is recommended based on age. Pharmacokinetic studies demonstrated generally similar pharmacokinetics between elderly subjects (>65 years) and younger adults (24 to 45 years).

Renal impairment: No dosage adjustment is required.

Hepatic impairment: No dosage adjustment is necessary in patients with mild to moderate hepatic impairment. Vortioxetine is not recommended in patients with severe hepatic impairment.

CYP2D6 poor metabolizers: Plasma concentrations of Vortioxetine may be approximately twice as high in CYP2D6 poor metabolizers compared to extensive metabolizers. Exposure may further increase in the presence of strong CYP3A4/2C9 inhibitors, and dose adjustment may be necessary.

Use in other patient populations: No dose adjustment is required based on race, gender, or ethnicity.

Limited data are available regarding Vortioxetine overdose. Medical monitoring and supportive care in a specialized healthcare setting are recommended.

Serotonin-norepinephrine reuptake inhibitor (SNRI)

Store at or below 30°C in a dry place, protected from light. Keep out of the reach of children.