General Information

Trintellix (vortioxetine) is a serotonin modulator and stimulator.

Trintellix is specifically indicated for Major Depressive Disorder in adults.

Trintellix is supplied as a tablet for oral administration. The recommended starting dose is 10 mg administered orally once daily without regard to meals. Dosage should then be increased 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.

Mechanism of Action

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

Clinical Trial Results

The FDA approval of Trintellix was based on six 6 to 8 week randomized, double-blind, placebo-controlled, fixed-dose studies (including one study in the elderly) and one maintenance study in adult inpatients and outpatients who met the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) criteria for MDD.
Adults (aged 18 years to 75 years)
The efficacy of Trintellix in subjects aged 18 years to 75 years was demonstrated in five 6 to 8 week, placebo-controlled studies. In these studies, subjects were randomized to Trintellix 5 mg, 10 mg, 15 mg or 20 mg or placebo once daily. For subjects who were randomized to Trintellix 15 mg/day or 20 mg/day, the final doses were titrated up from 10 mg/day after the first week. The primary efficacy measures were the Hamilton Depression Scale (HAMD-24) total score in Study 2 and the Montgomery-Asberg Depression Rating Scale (MADRS) total score in all other studies. In each of these studies, at least one dose group of Trintellix was superior to placebo in improvement of depressive symptoms as measured by mean change from baseline to endpoint visit on the primary efficacy measurement.
Elderly
The efficacy of Trintellix for the treatment of MDD was also demonstrated in a randomized, double-blind, placebo-controlled, fixed-dose study of Trintellix in elderly subjects (aged 64 years to 88 years) with MDD. Subjects received Trintellix 5 mg or placebo. The primary endpoints were also reached in this population.
Maintenance Study
In a non-US maintenance study 639 subjects meeting DSM-IV-TR criteria for MDD received flexible doses of Trintellix (5 mg or 10 mg) once daily during an initial 12 week open-label treatment phase; the dose of Trintellix was fixed during Weeks 8 to 12. Three hundred ninety six (396) patients who were in remission (MADRS total score =10 at both Weeks 10 and 12) after open-label treatment were randomly assigned to continuation of a fixed dose of Trintellix at the final dose they responded to (about 75% of patients were on 10 mg/day) during the open-label phase or to placebo for 24 to 64 weeks. Approximately 61% of randomized patients satisfied remission criterion (MADRS total score =10) for at least 4 weeks (since Week 8), and 15% for at least 8 weeks (since Week 4). Patients on Trintellix experienced a statistically significantly longer time to have recurrence of depressive episodes than did patients on placebo.