Does Brintellix Bring Anything New?

Does Brintellix Bring Anything New?After a dry spell of new antidepressants—the last one to be approved was levomilnacipran (Fetzima), the active enantiomer of milnacipran (Savella) in July 2013—the FDA approved vortioxetine (Brintellix) in September 2013. Vortioxetine is another serotonergic antidepressant. How exactly does it work, and what are its advantages over existing drugs?

Vortioxetine has several actions on serotonin-related targets. Like SSRIs, it’s a serotonin reuptake inhibitor. It’s also an agonist at 5-HT1A receptors as well as an antagonist of 5-HT3A and 5-HT7 receptors. (You may recall that buspirone (BuSpar), vilazodone (Viibryd), and aripiprazole (Abilify) are partial agonists of this receptor, among other functions.)

Thus, it sounds promising, but receptor-binding properties usually confer advantages that are only theoretical in nature. Therefore, a look at the data is appropriate.

Approval of vortioxetine was based on six short-term (6- to 8-week) studies of vortioxetine compared against placebo and/or duloxetine (Cymbalta) or venlafaxine (Effexor). These studies revealed that the effective doses of vortioxetine range from 5 to 20 mg/day, and also that vortioxetine was roughly similar in efficacy to venlafaxine but worse than duloxetine.

Other failed trials have been published, which generally used lower doses of vortioxetine (although some trials showed failure even at higher doses of 10 mg/day or 15 mg/day). A European trial found vortioxetine to be superior to agomelatine, an antidepressant whose manufacturer has not submitted it for FDA approval in the US due to lack of efficacy. As of summer 2013, there were 33 studies of vortioxetine registered with, for a range of diagnoses, so more data should be emerging.

In a longer-term trial, vortioxetine was found to be effective in preventing relapse in a 52-week study of adults with depression, although doses were low (2.5 to 10 mg/day) and the study was openlabel, with no placebo control. A short-term trial in elderly patients (ages 65 and older) also found it similar in efficacy to duloxetine.

The advantages of vortioxetine over existing agents remain to be seen. One possible advantage, which is already being discussed in the literature, is a “pro-cognitive” benefit due to its 5-HT7 antagonist properties. Compounds with this property have shown some benefit in animal models of learning and memory. Existing data in humans are minimal. As for side effects, the most common was dose-related nausea (reported by roughly 25% of subjects), while weight gain was negligible.

This article originally appeared in The Carlat Psychiatry Report -- an unbiased monthly covering all things psychiatry.
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TCPR’S VERDICT: Vortioxetine might be more than just a “me-too” drug, as its pharmacodynamic properties are slightly different from any existing agent on the market. But the data demonstrate no clear advantages over currently available drugs, and its cost is likely to be substantially higher than what’s available now. Further head-to-head trials with other antidepressants, as well as specific studies on purported advantages of vortioxetine, for example, in cognition, are necessary.

Does Brintellix Bring Anything New?

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This article was published in print 11/2013 in Volume:Issue 11:11.


APA Reference
Balt,, S. (2014). Does Brintellix Bring Anything New?. Psych Central. Retrieved on September 18, 2020, from


Scientifically Reviewed
Last updated: 9 Dec 2014
Last reviewed: By John M. Grohol, Psy.D. on 9 Dec 2014
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