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

Patient portrayal.
Individual results may vary.

Clinical Data

What might the role of efficacy be in the next chapter?

Adult MDD patients may suffer with different symptoms. In 6 clinical trials, TRINTELLIX was proven to relieve overall MDD symptoms1

Primary endpoints in randomized, double-blind, placebo-controlled, 6- to 8-week studies (5 mg to 20 mg once daily) in adult MDD patients.*1-7

  • 2 US studies (not reflected in data below) failed to show effectiveness at 5‑mg dose1

Efficacy demonstrated in multiple 6- to 8-week clinical trials of TRINTELLIX1

TRINTELLIX (vortioxetine) efficacy short term chart

The most common adverse reactions (incidence ≥5% and at least twice the rate of placebo in 6- to 8-week studies) were nausea, constipation, and vomiting.1

*Adult patients aged 18-75 in 5 studies and aged 64-88 in 1 elderly study.1
†Doses significantly superior to placebo after adjusting for multiplicity.1
‡Elderly patients can be at greater risk for hyponatremia.1

Abbreviations: HAM-D24, Hamilton Depression 24-item Rating Scale; LOCF, last observation carried forward; MADRS, Montgomery-Åsberg Depression Rating Scale; MDD, major depressive disorder; MMRM, mixed model repeated measures.

Only TRINTELLIX offers data on speed of processing during treatment of MDD in its US Prescribing Information

During the treatment of MDD, TRINTELLIX improved speed of processing, an aspect of cognitive function that may be impaired in MDD1

  • In adults with acute MDD, TRINTELLIX improved performance on the DSST, which most specifically measures speed of processing, in two 8-week, randomized, double-blind, placebo-controlled studies (dosed once daily)

The effects observed on DSST may reflect improvement in depression.1 Comparative studies have not been conducted to demonstrate a therapeutic advantage over other antidepressants on the DSST.

  • Common AEs (incidence ≥5% for TRINTELLIX) in Study 7 were nausea (16.4%, 20.8%, 4.1%) and headache (8.2%, 12.6%, 7.1%) for TRINTELLIX 10 mg/day, TRINTELLIX 20 mg/day, and placebo, respectively.8 SAEs were reported by two patients in the TRINTELLIX 20 mg group and two patients in the placebo group. Withdrawals due to TEAEs were 2.6% (TRINTELLIX 10 mg), 4.3% (TRINTELLIX 20 mg), and 4.1% (placebo).
  • Common AEs (incidence ≥5% for TRINTELLIX) in Study 8 were nausea (20.4%, 4.2%), headache (10.2%, 8.4%), and diarrhea (5.6%, 2.6%) for TRINTELLIX and placebo, respectively.9 Withdrawals due to TEAEs were 3.6% (TRINTELLIX 10 mg/20 mg) and 3.7% (placebo). One patient in the TRINTELLIX group attempted suicide, and one patient in the placebo group was hospitalized for worsening of depression.

†Doses are statistically significantly superior to placebo: P<.001 for Study 7 and P<.05 for Study 8.1,8-11

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TRINTELLIX has been studied in over 5,800 adults
with MDD between the ages of 18 and 88.1

Gregory Mattingly, MD headshot

Gregory Mattingly, MD

Washington University, Midwest Research Group, St. Charles, Missouri

"Data from 2 randomized long‑term studies demonstrated TRINTELLIX maintained efficacy in patients aged 18 to 75. In each study, patients who achieved remission during the open-label phase were randomized to TRINTELLIX or placebo in the double-blind phase.1 In both studies, patients randomized to TRINTELLIX were at a significantly less risk of recurrence in the double-blind phase,1,2 demonstrating that TRINTELLIX helped these patients reduce their risk of recurrence of depressive episodes."

Dr Mattingly is a physician and principal investigator in clinical trials for Midwest Research Group. He is also a founding partner of St. Charles Psychiatric Associates, where he treats adults, adolescents, and children with ADHD. Dr Greg Mattingly is board-certified in adult and adolescent psychiatry and has been a principal investigator in over 300 clinical trials focusing on ADHD and related conditions.

Having served on numerous national and international advisory panels, Dr Mattingly has received awards and distinctions for clinical leadership and neuroscience research. He currently serves on the board of directors for the American Professional Society of ADHD and Related Disorders (APSARD).

Dr Mattingly was paid as a consultant for Takeda and Lundbeck.

TRINTELLIX helped adult MDD patients in remission reduce their risk of recurrence of depressive episodes1  

Study 10 (US-based)

Randomized, double-blind, placebo-controlled, 2-phase study of 48 weeks in adult patients with MDD aged 18 to 75 years.1,10 Patients who met remission criteria* after 16-week, open-label treatment phase of TRINTELLIX 10 mg/day were randomized into double-blind phase 1:1:1:1 ratio to TRINTELLIX 5 mg/day, 10 mg/day, 20 mg/day, or placebo for 32 weeks.

TRINTELLIX (vortioxetine) efficacy long term chart (US)

Primary endpoint: Risk of recurrence† of a depressive episode was significantly greater for patients on placebo (n=151) vs TRINTELLIX (n=429) during the first 28 weeks of the double-blind phase (5 mg: HR, 1.9; 95% CI, 1.2-3.1; P=0.006. 10 mg: HR, 2.1; 95% CI, 1.3-3.4; P=0.002. 20 mg: HR, 2.1; 95% CI, 1.3-3.4: P=0.003).1,10 Significantly fewer patients taking TRINTELLIX experienced recurrence (19% [n=27], 18% [n=26], and 17% [n=25] for 5 mg, 10 mg, 20 mg, respectively; vs 33% [n=49] taking placebo, P<0.05).

Open-label period, AEs (≥5%)10

TRINTELLIX (vortioxetine) US Long Term Study Adverse Events Table (open-label)
  • 6% of patients withdrew due to TEAEs
  • 9 SAEs; only TRINTELLIX-related SAE was active suicidal ideation with a plan; 1 SAE was passive suicidal ideation

Double-blind period, AEs (≥5%) in at least 1 TRINTELLIX group10

TRINTELLIX (vortioxetine) US Long Term Study Adverse Events Table (double-blind)
  • Discontinuations (due to TEAEs): 2.0%, 2.1%, 0.7%, 4.9%, respectively
  • 9 SAEs; none deemed related to TRINTELLIX; 1 SAE was a completed suicide

IMPORTANT NOTE ABOUT MAINTENANCE STUDIES: The TRINTELLIX maintenance studies, Studies 9 and 10 in the Prescribing Information, are not comparable.1,10,12 Study 9 was conducted only ex-US while Study 10 was conducted in the US. In addition, patients in Study 10 were required to have been experiencing their current MDE longer, and to have had more previous MDEs. Also, lengths of the open-label and double-blind phases, dosing in each of these phases, criteria for randomization to the double-blind period, and primary endpoints differed between the studies. Each study should be considered independently.

*Remission was defined as MADRS total score ≤12 at both Weeks 14 and 16.1

†Recurrence of a depressive episode was defined as MADRS total score ≥22 or lack of efficacy as judged by the investigator.1

Abbreviations: AEs, adverse events; CI, confidence interval; HR, hazard ratio; MDE, major depressive episode; SAEs, serious adverse events; TEAEs, treatment-emergent adverse events.

Michele Novella, APRN-BC headshot

Michele Novella, APRN‑BC

Fairfield University, Medical Director and Owner of Star Psychiatric Healthcare, LLC, Danbury, Connecticut

"I will emphasize that TRINTELLIX has safety data up to 64 months in hundreds of patients."

Michele Novella, APRN-BC, is the medical director and owner of Star Psychiatric Healthcare in Danbury, CT. She is a past member of Western Connecticut Health Network’s (WCHN) medical staff where she worked in the Behavioral Health Department including Crisis Intervention, Intensive Outpatient Program running groups and teaching Dialectical Behavioral Therapy (DBT). In the Outpatient setting, Michele held several critical incident debriefings following traumatic events and losses that were experienced by the staff there.

After graduating from Fairfield University, Michele worked as a Registered Nurse at Memorial Sloan-Kettering Cancer Center in New York City. Later, she worked at WCHN’s inpatient oncology unit before being asked to serve as Nurse Manager for the Outpatient Oncology & Chemotherapy Infusion Services at Associated Internists of Danbury. During that time, she received the prestigious American Cancer Society’s State‑Wide “Excellence in Oncology Nursing Award” in 1991.

Michele later pursued her Master’s Degree of Nursing from Yale University, graduating with Honors. She is Board Certified by the ANCC as both a Clinical Nurse Specialist in Adult Psychiatric Nursing, as well as a Psychiatric Nurse Practitioner.

She holds specialized training in DBT and cognitive behavioral therapy (CBT) and Critical Incident Stress Debriefing. She held a pivotal role in the aftermath of the Sandy Hook Shootings and helped to organize and run the crisis services offered to the public at Newtown’s Reed Intermediate School and treated several of the Newtown Police Department’s first responders. She has been asked to speak to several groups on post‑traumatic stress disorder and stress responses after trauma.

Ms Novella was paid as a consultant for Takeda and Lundbeck.

Study 09 (Non-US)

Randomized, double-blind, placebo-controlled 2-phase study up to 64 weeks in adult patients with MDD aged 18 to 75 years.1,12 Patients who met remission criteria‡ after 12-week open-label phase of TRINTELLIX 5 mg/day or 10 mg/day were randomized to double-blind phase to continue final fixed dose or placebo.§

TRINTELLIX (vortioxetine) efficacy long term chart (non-US)

Primary endpoint: Risk of recurrence|| of a depressive episode was significantly greater for patients on placebo (n=192) vs TRINTELLIX (n=204) during the first 24 weeks of the double-blind phase (HR, 2.01; 95% CI, 1.26-3.21; P<0.01).1,12 Half as many patients experienced recurrence (13% [n=27] vs 26% [n=50], P<0.01).  

Note: One patient who was randomized to placebo in the double-blind period had an intentional overdose and alcohol poisoning in the post-dose period.12

†An overdose was predefined as an amount, such as number of tablets, greater than what had been prescribed for that patient.12

Open-label period, AEs (≥5%)11,12

TRINTELLIX (vortioxetine) Non-US long term study Adverse Events Table (open-label)
  • 87% of AEs were mild to moderate
  • 7.7% of patients withdrew due to AEs, most commonly: nausea, vomiting, headache, fatigue
  • 2.2% of patients had SAEs, none occurring in >1 patient, except depression (2 patients) 
  • 1 patient withdrawn due to score ≥5 on MADRS item 10 (suicidal thoughts)
  • 1 patient attempted suicide and was withdrawn; 1 patient had suicidal ideation but continued in the study

Double-blind period, AEs (≥5%) in TRINTELLIX group12

TRINTELLIX (vortioxetine) Non-US Long Term Study Adverse Events Table (double-blind)
  • In both groups, ~90% of AEs were mild to moderate
  • 2.6% (placebo) and 7.8% (TRINTELLIX) withdrew due to AEs
  • 4 patients (placebo) and 7 patients (TRINTELLIX) reported SAEs; none occurred in >1 patient except road traffic accident (2 patients)

‡Remission was defined as MADRS total score ≤10 at both Weeks 10 and 12.1
§Approximately 75% of patients were taking 10 mg/day.1
||Recurrence of a depressive episode was defined as MADRS total score ≥22 or lack of efficacy as judged by the investigator.1
An overdose was predefined as an amount, such as number of tablets, greater than what had been prescribed for that patient.12

Abbreviation: FAS, full analysis set.

Gregory Mattingly, MD headshot

Gregory Mattingly, MD

Washington University, Midwest Research Group, St. Charles, Missouri

"In my clinical opinion, the long‑term data for TRINTELLIX represent meaningful clinical data in the treatment of MDD."

Dr Mattingly is a physician and principal investigator in clinical trials for Midwest Research Group. He is also a founding partner of St. Charles Psychiatric Associates, where he treats adults, adolescents, and children with ADHD. Dr Greg Mattingly is board-certified in adult and adolescent psychiatry and has been a principal investigator in over 300 clinical trials focusing on ADHD and related conditions.

Having served on numerous national and international advisory panels, Dr Mattingly has received awards and distinctions for clinical leadership and neuroscience research. He currently serves on the board of directors for the American Professional Society of ADHD and Related Disorders (APSARD).

Dr Mattingly was paid as a consultant for Takeda and Lundbeck.

Efficacy observed as early as Week 2, with full effect seen as early as Week 42

Mean reduction from baseline in MADRS total score in Study 5 by study visit and at Week 8, the primary endpoint (FAS, MMRM)2,7

TRINTELLIX (vortioxetine) onset of action chart

In the 6- to 8-week placebo-controlled studies, the effect of TRINTELLIX, based on the primary efficacy measure, was generally observed starting at Week 2 and increased over subsequent weeks, with the full antidepressant effect generally not seen until Week 4 or later.1

Results from a randomized, double-blind, placebo-controlled, 8-week study (study 5) of adult patients aged 18-75 years with a primary diagnosis of MDD (n=462).6

In Study 5, the most common adverse reactions (incidence ≥5%) were nausea, headache, diarrhea, dizziness, constipation, vomiting, viral upper respiratory infection, and fatigue.6

*Doses significantly superior to placebo after adjusting for multiplicity

Abbreviations: MDD, major depressive disorder; MMRM, mixed model for repeated measures.

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  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.