VORTIOXETINE HYDROBROMIDE

Clinical safety rating: safe

MAOIs can cause serotonin syndrome Can cause nausea and increased risk of bleeding.

How it works

Vortioxetine is a serotonin modulator and stimulator. It acts as a 5-HT3 receptor antagonist, 5-HT1A receptor agonist, 5-HT1B receptor partial agonist, and inhibits the serotonin transporter (SERT), leading to increased serotonin concentrations in the synaptic cleft.

What the body does with it

Metabolism	Extensively metabolized primarily via CYP2D6, with minor contributions from CYP3A4, CYP2C9, CYP2C19, and CYP2A6. The major metabolite is an inactive carboxylic acid.
Excretion	Renal: <1% unchanged, fecal: primarily as metabolites (~59% fecal, ~26% urinary as conjugated metabolites)
Half-life	Terminal elimination half-life: ~66 hours (range 59-72 hours), allowing once-daily dosing.
Protein binding	~98-99% bound, primarily to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	Apparent Vd: ~2600 L (approximately 37 L/kg for a 70 kg individual), indicating extensive extravascular distribution.
Bioavailability	Oral: ~75% (range 73-83%), unaffected by food.
Onset of Action	Oral: clinical improvement (antidepressant effect) may begin within 1-2 weeks, with full effect often seen by 4-6 weeks.
Duration of Action	Due to long half-life, therapeutic effects persist for several days after discontinuation; steady state reached in ~2 weeks.

Classification & Brands

Dosing & administration

10 mg orally once daily; may increase to 20 mg once daily. Maximum 20 mg/day.

Dosage form	TABLET
Renal impairment	No dose adjustment required for GFR ≥15 mL/min. Not recommended for GFR <15 mL/min.
Liver impairment	Child-Pugh A: no adjustment. Child-Pugh B: reduce dose to 10 mg once daily. Child-Pugh C: not recommended.
Pediatric use	Not approved for patients <18 years of age.
Geriatric use	The recommended dose is 10 mg once daily; maximum dose 20 mg once daily, with careful titration due to increased sensitivity.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

MAOIs can cause serotonin syndrome Can cause nausea and increased risk of bleeding.

FDA category	Animal
Breastfeeding	Very limited data. VORTIOXETINE is excreted in rat milk; unknown in human milk. M/P ratio is not determined. Due to potential for adverse effects (sedation, reduced feeding), breastfeeding is not recommended during therapy, or consider discontinuing drug or breastfeeding.
Teratogenic Risk	Pregnancy category C. First trimester: limited human data; animal studies show no teratogenicity at exposures up to 20 times MRHD, but increased fetal mortality and delayed ossification at maternally toxic doses. Second/third trimester: neonatal adaptation syndrome (respiratory distress, feeding difficulties, jitteriness) reported with late third trimester use. Risk of persistent pulmonary hypertension of the newborn (PPHN) is not established.

Warnings & precautions

■ FDA Black Box Warning

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

Side Effect Profile

Common Effects	Nausea
Serious Effects

Absolute Contraindications

["Hypersensitivity to vortioxetine or any excipients","Concomitant use with monoamine oxidase inhibitors (MAOIs) or within 21 days of discontinuing MAOIs","Concomitant use with linezolid or intravenous methylene blue"]

Clinical Precautions

Precautions

["Suicidal thoughts and behaviors in pediatric and young adult patients","Serotonin syndrome or neuroleptic malignant syndrome-like reactions","Activation of mania/hypomania in patients with bipolar disorder","Angle-closure glaucoma (pupillary dilation)","Hyponatremia (especially in elderly or volume-depleted patients)","Abnormal bleeding (increased risk with NSAIDs, aspirin, anticoagulants)","Sexual dysfunction","Potential for cognitive and motor impairment"]

Clinical Tips & Counseling

Drug interactions

Loading safety data…

VORTIOXETINE HYDROBROMIDE

Clinical safety rating: safe

MAOIs can cause serotonin syndrome Can cause nausea and increased risk of bleeding.

How it works

What the body does with it

Metabolism	Extensively metabolized primarily via CYP2D6, with minor contributions from CYP3A4, CYP2C9, CYP2C19, and CYP2A6. The major metabolite is an inactive carboxylic acid.
Excretion	Renal: <1% unchanged, fecal: primarily as metabolites (~59% fecal, ~26% urinary as conjugated metabolites)
Half-life	Terminal elimination half-life: ~66 hours (range 59-72 hours), allowing once-daily dosing.
Protein binding	~98-99% bound, primarily to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	Apparent Vd: ~2600 L (approximately 37 L/kg for a 70 kg individual), indicating extensive extravascular distribution.
Bioavailability	Oral: ~75% (range 73-83%), unaffected by food.
Onset of Action	Oral: clinical improvement (antidepressant effect) may begin within 1-2 weeks, with full effect often seen by 4-6 weeks.
Duration of Action	Due to long half-life, therapeutic effects persist for several days after discontinuation; steady state reached in ~2 weeks.

Classification & Brands

Dosing & administration

10 mg orally once daily; may increase to 20 mg once daily. Maximum 20 mg/day.

Dosage form	TABLET
Renal impairment	No dose adjustment required for GFR ≥15 mL/min. Not recommended for GFR <15 mL/min.
Liver impairment	Child-Pugh A: no adjustment. Child-Pugh B: reduce dose to 10 mg once daily. Child-Pugh C: not recommended.
Pediatric use	Not approved for patients <18 years of age.
Geriatric use	The recommended dose is 10 mg once daily; maximum dose 20 mg once daily, with careful titration due to increased sensitivity.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

MAOIs can cause serotonin syndrome Can cause nausea and increased risk of bleeding.

FDA category	Animal
Breastfeeding	Very limited data. VORTIOXETINE is excreted in rat milk; unknown in human milk. M/P ratio is not determined. Due to potential for adverse effects (sedation, reduced feeding), breastfeeding is not recommended during therapy, or consider discontinuing drug or breastfeeding.
Teratogenic Risk	Pregnancy category C. First trimester: limited human data; animal studies show no teratogenicity at exposures up to 20 times MRHD, but increased fetal mortality and delayed ossification at maternally toxic doses. Second/third trimester: neonatal adaptation syndrome (respiratory distress, feeding difficulties, jitteriness) reported with late third trimester use. Risk of persistent pulmonary hypertension of the newborn (PPHN) is not established.

Warnings & precautions

■ FDA Black Box Warning

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

Side Effect Profile

Common Effects	Nausea
Serious Effects