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

Clinical Data

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

In 6 clinical studies, TRINTELLIX monotherapy delivered significant relief by reducing the overall symptoms of MDD1

Primary endpoint: improvement in MADRS or HAM-D24 total score.

Studies 1-6: short-term efficacy*

TRINTELLIX (vortioxetine) efficacy short-term chart

Results from the randomized, double‑blind, placebo‑controlled, 6‑ to 8‑week studies (5 mg to 20 mg once daily) in adult patients with MDD.

  • Two US studies (not reflected in the data below) failed to show effectiveness at the 5‑mg dose


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

HAM-D24, Hamilton Depression 24-item Rating Scale; LOCF, last observation carried forward; MADRS, Montgomery‑Åsberg Depression Rating Scale; MMRM, mixed model repeated measures.

More than 2300 patients were enrolled across these 6 clinical trials1

During the treatment of MDD, TRINTELLIX significantly improved speed of processing, which may be impaired in MDD.1

Endpoint measured: number of correct responses on the DSST

  • In adults with acute MDD, TRINTELLIX improved performance on the DSST, a neuropsychological test that most specifically measures speed of processing, in two 8-week, randomized, double-blind, placebo-controlled studies (dosed once daily).1 Speed of processing can be described as how quickly a person can accurately process information.8

Studies 7 and 8: improvement in speed of processing during the treatment of MDD1

TRINTELLIX (vortioxetine) study 7 and 8 chart

Doses are statistically significantly superior to placebo: P<.001 for Study 7 and P<.05 for Study 8.1,9-12

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.

ONLY TRINTELLIX has data on speed of processing during the treatment of MDD in its US Prescribing Information13

  • 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, and TRINTELLIX 20 mg/day, and placebo, respectively.9 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.10 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.


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

In long-term studies, TRINTELLIX monotherapy reduced the risk of recurrence of a depressive episode1

Study 10 (US-based)

Primary endpoint: risk of recurrence during the first 28 weeks of the double‑blind phase

Randomized, double‑blind, placebo‑controlled, 48-week, 2-phase study in adult patients with MDD aged 18 to 75 years.1,11 In the initial, open‑label phase, all patients (n=1106) were treated with TRINTELLIX 10 mg/day for 16 weeks. Patients who met remission criteria* after 16-week, open‑label treatment phase of TRINTELLIX 10 mg/day were randomized into a double-blind phase 1:1:1:1 ratio to TRINTELLIX 5 mg/day, 10 mg/day, 20 mg/day, or placebo for 32 weeks.

Study 10: risk of recurrence after remission1,11

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

*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

Percentage of patients with recurrence and percentage of patients recurrence-free at Week 28 were each divided by the total number of patients in study.11

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).1,11 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).

Study 10: long-term, 48-week study11

TRINTELLIX (vortioxetine) US Long-Term Study Adverse Events Table (open-label)

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

Open-label phase

  • 9 SAEs; only TRINTELLIX-related SAE was active suicidal ideation with a plan; 1 SAE was passive suicidal ideation11

Double-blind phase

  • 9 SAEs; none deemed related to TRINTELLIX; 1 SAE was a completed suicide11

IMPORTANT NOTE ABOUT MAINTENANCE STUDIES: The TRINTELLIX maintenance studies, Studies 9 and 10 in the Prescribing Information, are not comparable.1,11,14 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.

Study 09 (Non-US)1,14

Primary endpoint: time to recurrence within the first 24 weeks of the double‑blind period

Randomized, double-blind, placebo‑controlled 2-phase study up to 64 weeks in adult patients with MDD aged 18 to 75 years. In the initial, open‑label phase, all patients (n=639) received flexible doses of TRINTELLIX (5 mg or 10 mg)* once daily for 12 weeks. 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.§

Study 9: long-term efficacy

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). Half as many patients experienced recurrence (13% [n=27] vs 26% [n=50], P<0.01).  

Study 9 open-label phase, AEs (incidence, ≥5%)12,14

TRINTELLIX (vortioxetine) 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; neither attempt nor ideation was related to TRINTELLIX.

Study 9 double-blind phase, AEs in at least 1 TRINTELLIX group (incidence, ≥5%)14

TRINTELLIX (vortioxetine) Non-US Long-Term Study Adverse Events Table (double-blind)
  • In both groups, ~90% of AEs were mild to moderate4
  • 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)

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.

*The dose of TRINTELLiX was fixed during Weeks 8 to 12.1
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.14

Abbreviation: FAS, full analysis set.

Patients experienced relief from symptoms as early as Week 2 with the full antidepressant effect not seen until Week 4 or later1

Study 5: time course of treatment response6

TRINTELLIX (vortioxetine) onset of action chart

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 Chart shows mean reduction from baseline in MADRS total score at each visit (FAS, MMRM).

Based on the primary efficacy measure, the effect of TRINTELLIX 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

*Doses significantly superior to placebo after adjusting for multiplicity

Abbreviations: MMRM, mixed model for repeated measures.


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  1. Trintellix (vortioxetine) prescribing information. Takeda Pharmaceuticals.
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  11. Data on file. Takeda Pharmaceuticals.
  12. Data on file. Lundbeck.
  13. FDA updates Trintellix® (vortioxetine) label to include data showing improvement in processing speed, an important aspect of cognitive function in acute Major Depressive Disorder (MDD). News release. GlobeNewswire. May 2, 2018.
  14. Boulenger J-P, Loft H, Florea I. J Psychopharmacol. 2012;26(11):1408‑1416.
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  17. 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.