Major Depressive Disorder
Vortioxetine hydrobromide is used for the treatment of major depressive disorder in adults.
The American Psychiatric Association (APA) states that the effectiveness of antidepressants in the treatment of major depressive disorder is generally comparable between and within classes of these medications, including selective serotonin-reuptake inhibitors (SSRIs), serotonin- and norepinephrine-reuptake inhibitors (SNRIs), tricyclic antidepressants, monoamine oxidase (MAO) inhibitors, and other antidepressants (e.g., bupropion, mirtazapine, trazodone). Therefore, the initial selection of an antidepressant can be based mainly on the following factors: patient preference; nature of prior response to medication; safety, tolerability, and anticipated adverse effects; concurrent psychiatric and medical conditions; specific properties of the medication (e.g., half-life, actions on cytochrome P-450 [CYP] isoenzymes, other drug interactions); and cost. For most patients, an SSRI, SNRI, mirtazapine, or bupropion is considered optimal based on these considerations. Clinicians may consult APA's Practice Guidelines for the Treatment of Patients with Major Depressive Disorder (at http://www.psychiatryonline.com/pracGuide/pracGuideTopic_7.aspx) for additional information.
The short-term antidepressant efficacy of vortioxetine was established in 6 randomized, double-blind, placebo-controlled, fixed-dose studies of 6-8 weeks' duration in adult inpatients and outpatients who met DSM-IV-TR criteria for major depressive disorder, including one study in geriatric patients. In 5 of these studies, adult patients 18-75 years of age were randomized to receive either vortioxetine 5, 10, 15, or 20 mg or placebo given once daily. The primary efficacy measure was the Hamilton Depression Scale (HAMD-24) total score in one study (study 2) and the Montgomery-Asberg Depression Rating Scale (MADRS) total score in the other studies. In each of these studies, at least one dosage group of vortioxetine was found to be more effective than placebo in improving depressive symptoms as measured by the mean change from baseline to end point visit on the HAMD-24 or MADRS total score. The remaining study (study 6) demonstrated the antidepressant efficacy of vortioxetine (5 mg once daily) in geriatric patients 64-88 years of age with recurrent major depressive disorder (with at least one previous episode before the age of 60 years) and without concomitant cognitive impairment.
(See Geriatric Use under Warnings/Precautions: Specific Populations, in Cautions.)An antidepressant effect was generally observed in vortioxetine-treated patients beginning at week 2 and increased during subsequent weeks; the full antidepressant effect generally was not seen until week 4 or later. No age-, gender-, or race-related differences in response to vortioxetine were noted in the adult studies.
Two randomized, double-blind, placebo-controlled studies of vortioxetine 5 mg once daily conducted in the US failed to demonstrate effectiveness of this dosage in the treatment of major depressive disorder in adults.
In a long-term, multicenter, non-US maintenance study, 639 adult inpatients or outpatients who met DSM-IV-TR criteria for major depressive disorder initially received open-label vortioxetine therapy (given in a flexible dosage of 5 or 10 mg once daily during the first 8 weeks of the initial 12-week treatment phase; dosage was fixed between weeks 8-12). Patients in remission at weeks 10 and 12 were then randomized either to continue fixed-dosage vortioxetine therapy at the final dosage they had responded to (approximately 75% were receiving 10 mg daily) or to receive placebo for 24-64 weeks. Patients receiving vortioxetine experienced a longer time to recurrence of depressive episodes compared with patients receiving placebo. In addition, fewer patients receiving vortioxetine (13%) experienced a relapse compared with those receiving placebo (26%). In 2 additional long-term (52-week), multicenter, open-label, extension studies, vortioxetine (2.5-10 mg once daily) was found to be effective and well tolerated in adults with major depressive disorder. Laboratory, vital sign, and ECG findings in these 2 studies did not reveal any clinically important safety issues with long-term vortioxetine therapy.