WHAT MIGHT THE

ROLE OF EFFICACY

BE IN THE NEXT

CHAPTER?

Patient portrayal.
Individual results may vary.

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

 

In 6 short-term studies, TRINTELLIX was proven to help with overall MDD symptoms1

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

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

  

TRINTELLIX (vortioxetine) efficacy short term chart

Most common adverse reactions (incidence ≥5% and at least twice the rate of placebo in 6- to 8-week studies) were nausea, constipation, and vomiting1

*Five studies in adults aged 18 to 75 years; One dedicated study in elderly patients aged 64 to 88 years.1

Doses that are statistically significantly superior to placebo after adjusting for multiplicity.1



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)1
TRINTELLIX (vortioxetine) study 7 and 8 chart

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 the FOCUS study (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.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 in the CONNECT study (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

TRINTELLIX MAINTAINED EFFICACY for MDD IN 2 LONG-TERM STUDIES

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.1,12,13 Patients in remission* 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)

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; primary endpoint).15 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%)14

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 in at least 1 TRINTELLIX group (≥5%)14 –

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.1,14,16 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 reactions; TEAEs, treatment-emergent adverse events.

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.1,16 Patients in remission 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



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; primary endpoint).16 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.16

– Open-label PERIOD, AEs (≥5%)16,17

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
72.2% 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 deemed related to TRINTELLIX
 

– Double-blind period, AEs in TRINTELLIX group (≥5%)16

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.16

Abbreviation: FAS, full analysis set.


Learn more about TRINTELLIX

IMPORTANT SAFETY INFORMATION

SEE LESS

Warning: Suicidal Thoughts & Behaviors

  • 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.

CONTRAINDICATIONS

  • 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.

WARNINGS AND PRECAUTIONS

  • 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, fentanyl, lithium, tramadol, 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.

ADVERSE REACTIONS

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.

DRUG INTERACTIONS

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

PREGNANCY

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.

INDICATION

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 https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/

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