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Comparative Evaluation: Switching Antidepressant Therapy in Patients With Major Depressive Disorder.

Clinical Study Title:

Comparative Evaluation of Vortioxetine as a Switch Therapy in Patients With

Major Depressive Disorder

Clinical Study Abstract:

Vortioxetine is an approved antidepressant with a multimodal mechanism of action different from that of selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs). The present analysis and review of the efficacy and tolerability of switching to vortioxetine includes 3 published studies of patients with major depressive disorder (MDD) switched from SSRI/SNRI therapy to vortioxetine due to lack of efficacy or tolerability. The REVIVE study (A Study of Vortioxetine in Comparison to Agomelatine in Adults Suffering From Major Depression With an Inadequate Response to Previous Medication) allowed for direct comparison with agomelatine. Like vortioxetine, agomelatine has a mechanism of action that is different from SSRIs and SNRIs. In addition, indirect treatment comparison (ITC) was performed with vortioxetine vs sertraline, venlafaxine, bupropion, and citalopram using extant switch studies published in the biomedical literature. Finally, the impact on


SSRI-induced treatment-emergent sexual dysfunction (TESD) was assessed directly, with escitalopram as a comparator, in stable patients with MDD in the NCT01364649 trial (Vortioxetine 10 and 20 mg for Treatment of Major Depressive Disorder With Sexual Dysfunction). Tolerability with vortioxetine in the switch population was compared to the overall MDD population. In the REVIVE study, vortioxetine demonstrated significant benefits over agomelatine on efficacy, functioning, and quality-of-life outcomes, with fewer withdrawals due to adverse events (AEs). In the ITC analysis, vortioxetine had numerically higher remission rates vs all therapies included. Withdrawal rates due to AEs were significantly lower for vortioxetine vs sertraline, venlafaxine, and bupropion, and numerically lower vs citalopram. Switching to vortioxetine was statistically superior to escitalopram in improving TESD. Tolerability was similar in the switch population and the overall MDD population.

Comparative Evaluation of Vortioxetine

In clinical practice, some 40-60% of patients with MDD do not respond adequately to first-line pharmacotherapies (eg, they do not achieve [greater than or equal to]50% reduction in depression rating scores). Switching antidepressant therapy is a commonly used strategy when the initial course of antidepressant therapy is either ineffective or poorly tolerated; however, once the decision is made to switch antidepressants, there is often limited evidence to guide the choice of which new agent to prescribe. For a patient who does not respond adequately to his or her initial or current treatment, the decision about the next course of treatment is multifaceted often includes factors such as the patients clinical profile, treatment history, and individual preferences. Patients who do not respond to SSRIs and SNRIs that are typically prescribed in the first 2 lines of treatment may require the use of novel medications with different mechanisms of action.

Using a network-of-evidence approach for the indirect comparison of treatments (see table), vortioxetine was found to be numerically more efficacious and better tolerated than a variety of comparator antidepressants commonly prescribed in clinical practice. Furthermore, compared with escitalopram, vortioxetine demonstrated greater improvement in sexual functioning, with no loss of efficacy, in patients who were well treated on their previous antidepressant but who switched from an SSRI due to intolerable sexual side effects.


Thase ME, Danchenko N, Brignone M, et al.

Comparative evaluation of vortioxetine as a switch therapy in patients with major depressive disorder. Eur Neuropsychopharmacol. June 26, 2017. pii: S0924-977X (17)30254-7.


Bauer M, Pfennig A, Severus E, et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders, part 1: update 2013 on the acute and continuation treatment of unipolar depressive disorders. World J Biol Psychiatry. 2013;14:334-385.

Jacobsen PL, Mahableshwarkar AR, Chen Y, et al. 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.

Kasper, S, Hajak, G. The efficacy of agomelatine in previously treated depressed patients. Eur Neuropsychopharmacol. 2013;23:814-821.

Lenox-Smith, AJ, Jiang Q. Venlafaxine extended release versus citalopram in patients with depression unresponsive to a selective serotonin reuptake inhibitor. Int Clin. Psychopharmacol. 2008;23:113-119.

Montgomery SA, Nielsen, RZ, Poulsen, LH et al. A randomized, double blind study in adults with major depressive disorder with an inadequate response to a single course of selective serotonin reuptake inhibitor or serotonin--noradrenaline reuptake inhibitor treatment switched to vortioxetine or agomelatine. Hum Psychopharmacol Clin Exp. 2014;29:470-482.

Rush AJ, Trivedi MH, Wisniewski SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR'D report. Am J Psychiatry. 2006;163(11):1905-1917.

Caption: Michael E. Thase, MD Professor of Psychiatry Director, Mood and Anxiety Disorders Treatment and Research Program University of Pennsylvania

Please Note: Illustration(s) are not available due to copyright restrictions.
Source Studies for Comparative Evaluation

Comparator      Source Studies
Agomelatine     Direct comparison in REVIVE
Sertraline      ITC combining REVIVE and Kasper 2013
Venlafaxine XR  ITC combining REVIVE, Kasper 2013, and STAR*D
Bupropion XR    ITC combining REVIVE, Kasper 2013, and STAR*D
Citalopram      ITC combining REVIVE, Kasper 2013, STAR*D, and
                Lenox-Smith 2008
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Publication:Internal Medicine News
Date:Nov 1, 2017
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