Table 1.

Clinical summary of vortioxetine (Brintellix^®)

Class of agent	• N06AX26, other, antidepressants (ATC)a
	• Antidepressant with multimodal mechanism of actionb
Formulation	Solid oral tablets (5, 10, and 20 mg)
Starting dose	10 mg/day, once daily (then increase as tolerated to target dose of 20 mg/day)
Effective dose range	5 to 20 mg, once daily
Approved indication	Major depressive disorder, adults
Pharmacokinetics	• Oral bioavailability: 75%
	• T1/2 : 57–66 hours
	• Metabolism: CYP2D5 (primary), CYP3A4/5, CYP2C9, CYP2C19, CYP2C8, CYP2A6, and CYP2B6
Pharmacodynamics	• SERT inhibitor
	• Antagonist: 5-HT3, 5-HT7, 5-HT1D
	• Partial agonist: 5-HT1B
	• Agonist: 5-HT1A
Drug interactions/dose adjustments	• Reduce dose by 50% when administered to a pharmacogenetic poor CYP2D6 metabolizer, or when given concomitantly with a strong CYP2D6 inhibitor.
	• Higher doses may be required when given concomitantly with a strong CYP3A4 inducer.
	• No dose adjustments are required on the basis of patient age, sex, or race.
	• No dose adjustments are required in patients with mild to moderate renal or hepatic impairment.
Contraindications/precautions	• Coadministration with a monoamine oxidase inhibitor is contraindicated.
	• Use in patients with severe hepatic impairment is not recommended.
	• The vortioxetine drug label has the antidepressant class warning about the potential for increased risk of suicidal thoughts and behavior in children, adolescents, and young adults.c
Pregnancy and breastfeeding	• US Food and Drug Administration safety in pregnancy category: Cd
	• Lactational safety profile of vortioxetine: unknown
Use in children and adolescent	• The effectiveness and safety of vortioxetine for any indication has not been studied in children or adolescents
Geriatric adults	• Positive randomized trial in geriatric adults (Table 3)
	• No dose adjustment required based on age

Notes:

^aRefers to the WHO ATC code for vortioxetine as agreed upon at the March 2014 meeting of the WHO International Working Group for Drug Statistics Methodology (see http://www.who.int/medicines/publications/druginformation/issues/DrugInformation2014_Vol28-4/en/).

^bRefers to vortioxetine’s designation under the psychotropic medication reclassification system proposed by the European College of Neuropsychopharmacology, in collaboration with the American College of Neuropsychopharmacology, the Asian College of Neuropsychopharmacology, the International College of Neuroopsychopharmacology, and the International Union of Basic and Clinical Pharmacology (see http://www.ecnp.eu/projects-initiatives/nomenclature.aspx).

^cClose monitoring for the emergence of suicidal thoughts and behavior is recommended for patients at any age who are started on antidepressant treatment. Vortioxetine has not been studied for any indication in children and adolescents.

^dNo adequately controlled studies of vortioxetine in pregnant women. The package label references no teratogenic effects in rodents administered 58–77 times the maximum recommended human dose (20 mg) during pregnancy. Vortioxetine should be used in pregnancy only if potential benefits outweigh potential risks to the developing fetus.

Abbreviations: ATC, Anatomic Therapeutic Classification; WHO, World Health Organization; T_1⁄2, mean elimination half-life; CYP, cytochrome P450; SERT, serotonin transporter.