HCP Frequently Asked Questions | TRINTELLIX (vortioxetine)

TRINTELLIX® (vortioxetine) is indicated for the treatment of Major Depressive Disorder (MDD) in adults.


Selective serotonin reuptake inhibitors (SSRIs) are a common type of antidepressant used to treat Major Depressive Disorder (MDD) by enhancing specific serotonergic activity in the CNS.14

The mechanism of the antidepressant effect of TRINTELLIX is not fully understood, although it is thought to be related to its enhancement of serotonergic activity through inhibition of the reuptake of serotonin (5-HT).1 It also has several other activities including 5-HT3 receptor antagonism and 5-HT1A receptor agonism. The contribution of these activities to TRINTELLIX's antidepressant effect has not been established.

For descriptions and symptoms of MDD, and a hypothetical patient profile, please see Diagnostic Criteria & Patient Profile

The mean terminal half-life of TRINTELLIX is approximately 66 hours, and steady-state plasma concentrations are typically achieved within two weeks of dosing.1

Multiple drugs have the potential to interact with TRINTELLIX, including prescription and over-the-counter medicines, vitamins, and herbal supplements. TRINTELLIX and some drugs should not be taken concomitantly as co-administration may lead to serious side effects or decreases in efficacy.1

See below for clinically important interactions with TRINTELLIX.1

NOTE: this is not an exhaustive list of TRINTELLIX drug interactions. Please see the Full Prescribing Information for further information.

Monoamine Oxidase Inhibitors (MAOIs)

Clinical Impact

The concomitant use of SSRIs and SNRIs including TRINTELLIX with MAOIs increases the risk of serotonin syndrome.


Concomitant use of TRINTELLIX is contraindicated:

  • With an MAOI intended to treat psychiatric disorders or within 21 days of stopping treatment with TRINTELLIX.
  • Within 14 days of stopping an MAOI intended to treat psychiatric disorders.
  • In a patient who is being treated with linezolid or intravenous methylene blue.

selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue

Other Serotonergic Drugs

Clinical Impact

Concomitant use of TRINTELLIX with other serotonergic drugs increases the risk of serotonin syndrome.


Monitor for symptoms of serotonin syndrome when TRINTELLIX is used concomitantly with other drugs that may affect the serotonergic neurotransmitter systems. If serotonin syndrome occurs, consider discontinuation of TRINTELLIX and/or concomitant serotonergic drugs.


Other SNRIs, SSRIs, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, amphetamines, tryptophan, and St. John’s Wort

Strong Inhibitors of CYP2D6

Clinical Impact

Concomitant use of TRINTELLIX with strong CYP2D6 inhibitors increases plasma concentrations of vortioxetine.


Reduce TRINTELLIX dose by half when a strong CYP2D6 inhibitor is coadministered.


bupropion, fluoxetine, paroxetine, quinidine

Strong CYP Inducers

Clinical Impact

Concomitant use of TRINTELLIX with strong CYP inducer decreases plasma concentrations of vortioxetine.


Consider increasing the TRINTELLIX dose when a strong CYP inducer is coadministered. The maximum dose is not recommended to exceed three times the original dose.


rifampin, carbamazepine, phenytoin

Drugs that interfere with Hemostasis (antiplatlet agents and anticoagulants)

Clinical Impact

Concomitant use of TRINTELLIX with an antiplatelet or anticoagulant drug may potentiate the risk of bleeding.


Inform patients of the increased risk of bleeding associated with the concomitant use of TRINTELLIX and antiplatelet agents and anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio.


aspirin, clopidogrel, heparin, warfarin

Drugs Highly Bound to Plasma Protein

Clinical Impact

TRINTELLIX is highly bound to plasma protein. The concomitant use of TRINTELLIX with another drug that is highly bound to plasma protein may increase free concentrations of TRINTELLIX or other tightly-bound drugs in plasma.


Monitor for adverse reactions and reduce dosage of TRINTELLIX or other protein bound drugs as warranted.



The list price for TRINTELLIX is $466.35 for a 30-day prescription.* Eligible commercially insured patients may pay as little as $10 for either a 30-day or 90-day prescription with the TRINTELLIX savings card. Savings of up to $100 per 30-day or $300 per 90-day prescription, with a maximum total savings of up to $1,300 over one year. Restrictions apply.

TRINTELLIX is available for ~85% of commercially insured patients in the US without prior authorization (PA).

For more information about savings or for coverage in your area, visit Savings & Support.

*As of 01/03/2023.
See the savings card for Eligibility Requirements and Terms & Conditions.
Formulary data are provided by Fingertip Formulary® and are current as of September 2022. Check the patient’s individual health plan for coverage and cost information, which may change without notice.

Contact your local sales rep to request samples; if you don’t have one, you can request a rep here.

If you would like to have TRINTELLIX samples shipped to your office, please visit MySampleCloset and follow the steps below:

  • Login or register to create a new account (upon initial login, you may be prompted to complete a few security questions)
  • View the list of products and select TRINTELLIX
  • Place and submit your order. Maximum order quantities are listed on the site, one order may be placed per month.

Please note that when a TRINTELLIX sample order is placed on the MySampleCloset website, your local Takeda representative will be notified so that they can expedite delivery by bringing them to your office personally. If the representative is unable to deliver your order, the samples will be shipped to your office.

TRINTELLIX is available in 5 mg, 10 mg, and 20 mg tablets.1

For more information, visit our Dosing page, or see Full Prescribing Information.

The recommended starting dose of TRINTELLIX is 10 mg administered orally once daily without regard to meals.1 Dosage can then be titrated 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.

Prior to initiating treatment with TRINTELLIX, screen patients for personal or family history of bipolar disorder, mania, or hypomania.1

Although patients can abruptly discontinue therapy with TRINTELLIX, it is recommended that doses of 15 mg/day or 20 mg/day be reduced to 10 mg/day for one week prior to full discontinuation if possible.1

The maximum recommended dose is 10 mg/day in known CYP2D6 poor metabolizers.1

In placebo-controlled trials, some patients taking more than 10 mg/day experienced transient adverse reactions such as headache and muscle tension following abrupt discontinuation.1

For more information, visit our Dosing page, or see Full Prescribing Information.

This reflects the FDA-approved label dosage information. Neither Takeda nor Lundbeck can suggest treatment approaches or make recommendations for the management of patients.

For full information on treatment-related side effects and adverse reactions, see Safety DataImportant Safety Information, and the Full Prescribing Information.



  • Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies.
  • Closely monitor all antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors.
  • TRINTELLIX is not approved for use in pediatric patients.


  • Hypersensitivity: Hypersensitivity to vortioxetine or any component of the TRINTELLIX formulation. Hypersensitivity reactions including anaphylaxis, angioedema, and urticaria have been reported in patients treated with TRINTELLIX.
  • Monoamine Oxidase Inhibitors (MAOIs): Do not use MAOIs intended to treat psychiatric disorders with TRINTELLIX or within 21 days of stopping treatment with TRINTELLIX, due to an increased risk of serotonin syndrome. Do not use TRINTELLIX within 14 days of stopping an MAOI intended to treat psychiatric disorders.
  • Linezolid and Methylene Blue: Do not start TRINTELLIX in a patient being treated with MAOIs such as linezolid or intravenous methylene blue, due to an increased risk of serotonin syndrome.


  • Suicidal Thoughts and Behaviors in Adolescents and Young Adults: Monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of drug therapy, and at times of dosage changes. Counsel family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider. Consider changing the therapeutic regimen, including possibly discontinuing TRINTELLIX, in patients whose depression is persistently worse, or who are experiencing emergence of suicidal thoughts and behaviors. In pooled analyses of placebo-controlled trials of antidepressants, the incidence of suicidal thoughts and behaviors in antidepressant-treated patients ages 24 and younger was greater than in placebo-treated patients.
  • Serotonin Syndrome: The development of a potentially life-threatening serotonin syndrome has been reported with serotonergic antidepressants, including TRINTELLIX, when used alone but more often when used concomitantly with other serotonergic drugs (including triptans, tricyclic antidepressants, opioids [e.g., fentanyl and tramadol], lithium, tryptophan, buspirone, and St. John's Wort), and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Monitor patients for emergence of serotonin syndrome. If concomitant use of serotonergic antidepressants, including TRINTELLIX, is clinically warranted, make patients aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases. If symptoms occur, immediately discontinue TRINTELLIX and any concomitant serotonergic agents, and initiate supportive symptomatic treatment.
  • Increased Risk of Bleeding: The use of drugs that interfere with serotonin reuptake inhibition, including TRINTELLIX, may increase the risk of bleeding events. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), warfarin, and other anticoagulants may add to this risk. Inform patients about the increased risk of bleeding when TRINTELLIX is coadministered with NSAIDs, aspirin, or other drugs that affect coagulation or bleeding.
  • Activation of Mania/Hypomania: In patients with bipolar disorder, treating a depressive episode with TRINTELLIX or another antidepressant may precipitate a mixed/manic episode. Prior to initiating treatment with TRINTELLIX, screen patients for any personal or family history of bipolar disorder, mania, or hypomania.
  • Discontinuation Syndrome: Adverse reactions have been reported upon abrupt discontinuation of treatment with TRINTELLIX at doses of 15 mg/day and 20 mg/day. A gradual reduction in dosage rather than abrupt cessation is recommended whenever possible.
  • Angle-Closure Glaucoma: The pupillary dilation that occurs following use of many antidepressant drugs, including TRINTELLIX, may trigger an angle-closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy.
  • Hyponatremia: Hyponatremia has occurred as a result of treatment with serotonergic drugs, including TRINTELLIX, and in many cases appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Elderly patients and patients taking diuretics or who are otherwise volume-depleted can be at greater risk. Symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which can lead to falls. More severe and/or acute cases have included hallucination, syncope, seizure, coma, respiratory arrest, and death. Discontinue TRINTELLIX in patients with symptomatic hyponatremia and institute appropriate medical intervention.
  • Sexual Dysfunction: Use of serotonergic antidepressants, including TRINTELLIX, may cause symptoms of sexual dysfunction. In male patients, serotonergic antidepressant use may result in ejaculatory delay or failure, decreased libido, and erectile dysfunction. In female patients, use may result in decreased libido and delayed or absent orgasm.


The most commonly observed adverse reactions for TRINTELLIX in 6- to 8-week placebo-controlled studies (incidence ≥5% and at least twice the rate of placebo) were: nausea, constipation, and vomiting.


Concomitant administration of TRINTELLIX and strong CYP2D6 inhibitors or strong CYP inducers may require a dose adjustment of TRINTELLIX.


Exposure to serotonergic antidepressants, including TRINTELLIX, in late pregnancy may increase the risk for neonatal complications requiring prolonged hospitalization, respiratory support, and tube feeding, and/or persistent pulmonary hypertension of the newborn (PPHN). Monitor neonates who were exposed to TRINTELLIX in the third trimester for PPHN and drug discontinuation syndrome.


TRINTELLIX is indicated for the treatment of Major Depressive Disorder (MDD) in adults.

Please click for Full Prescribing Information.

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at 

  1. Trintellix (vortioxetine) prescribing information. Takeda Pharmaceuticals.
  2. Alvarez E, Perez V, Dragheim M, Loft H, Artigas F. A double-blind, randomized, placebo-controlled, active reference study of LuAA21004 in patients with Major Depressive Disorder. Int J Neuropsychopharmacol. 2012;15(5):589-600.
  3. Henigsberg N, Mahableshwarkar AR, Jacobsen P, Chen Y, Thase ME. A randomized, double-blind, placebo-controlled 8-week trial of the efficacy and tolerability of multiple doses of Lu AA21004 in adults with Major Depressive Disorder. J Clin Psychiatry. 2012;73(7):953-959.
  4. Boulenger J-P, Loft H, Olsen CK. Efficacy and safety of vortioxetine (Lu AA21004), 15 and 20 mg/day: a randomized, double-blind, placebo-controlled, duloxetine-referenced study in the acute treatment of adult patients with Major Depressive Disorder. Int Clin Psychopharmacol. 2014;29(3):138-149.
  5. Mahableshwarkar AR, Jacobsen P, Chen Y, Serenko M, Trivedi MH. A randomized, double-blind, duloxetine-referenced study comparing efficacy and tolerability of 2 fixed doses of vortioxetine in the acute treatment of adults with MDD. Psychopharmacology (Berl). 2015;232(12):2061-2070.
  6. Jacobsen P, Mahableshwarkar AR, Serenko M, Chan S, Trivedi MH. A randomized, double-blind, placebo-controlled study of the efficacy and safety of vortioxetine 10 mg and 20 mg in adults with Major Depressive Disorder. J Clin Psychiatry. 2015;76(5):575-582.
  7. Katona C, Hansen T, Olsen CK. A randomized, double-blind, placebo-controlled, duloxetine-referenced, fixed-dose study comparing the efficacy and safety of Lu AA21004 in elderly patients with Major Depressive Disorder. Int Clin Psychopharmacol. 2012;27(4):215-223.
  8. McIntyre RS, Lophaven S, Olsen CK. A randomized, double-blind, placebo-controlled study of vortioxetine on cognitive function in depressed adults. Int J Neuropsychopharmacol. 2014;17(10):1557-1567.
  9. Mahableshwarkar AR, Zajecka J, Jacobson W, Chen Y, Keefe RSE. A randomized, placebo-controlled, active-reference, double-blind, flexible-dose study of the efficacy of vortioxetine on cognitive function in Major Depressive Disorder. Neuropsychopharmacology. 2015;40(8):2025-2037.
  10. Data on file. Takeda Pharmaceuticals.
  11. Data on file. Lundbeck.
  12. Boulenger J-P, Loft H, Florea I. A randomized clinical study of Lu AA21004 in the prevention of relapse in patients with Major Depressive Disorder. J Psychopharmacol. 2012;26(11):1408-1416.
  13. Jacobsen PL, Mahableshwarkar AR, Chen Y, Chrones L, Clayton AH. Effect of vortioxetine vs. escitalopram on sexual functioning in adults with well-treated Major Depressive Disorder experiencing SSRI-induced sexual dysfunction. J Sex Med. 2015;12(10):2036-2048.
  14. Kambeitz JP, Howes OD. The serotonin transporter in depression: Meta-analysis of in vivo and post mortem findings and implications for understanding and treating depression. J Affect Disord. 2015;186:358-366.
  15. American Psychiatric Association. Depressive disorders. In: Diagnostic and Statistical Manual of Mental Disorders. 5th edition (DSM-5®). Arlington, VA: American Psychiatric Association; 2013:155-188.
  16. ICD-10-CM Tabular list of diseases and injuries. Centers for Medicare & Medicaid Services. Published 2022. https://www.cms.gov/files/zip/2022-code-tables-tabular-and-index-updated-02012022.zip. Accessed August 19, 2022.