Monday, November 9, 2015


Vortioxetine is one of the newest antidepressants on the market, released in the U.S. in 2013.  It has serotonin and norepinephrine reuptake inhibition effects, plus a variety of direct effects on serotonin receptors. 

This is a negative study of vortioxetine, showing that it did not lead to any difference in rating scores compared to placebo, when used at doses of 10 mg or 15 mg daily, to treat depression for 8 weeks:

In another study, by Jacobson et al (2015), looking at doses of 10 mg or 20 mg daily, they found slight improvements in the vortioxetine groups compared to placebo, with "significant" differences in the MADRS score only for the 20 mg dose ( ).  If you look at the symptom changes vs. placebo on a graph, the clinical relevance of the vortioxetine effect appears questionable.  Yet, typically with papers of this type, despite the results being very unimpressive, the authors try to frame it in a very positive way, as though they had discovered a fantastically effective new treatment.  Vortioxetine is supposed to be helpful for managing sexual side effects as well, but the measures of this done in the study once again do not show a spectacular benefit.  For those who did not have sexual side effects previously, about half in the vortioxetine group developed sexual side effects, at a rate 10-20% greater than placebo.   Here are the authors' final assertions at the end of their paper:   "In conclusion, vortioxetine 20 mg significantly reduced MADRS total score at 8 weeks in adults with MDD. Overall, vortioxetine was well tolerated in this study."   Perhaps a more fair conclusion could be "vortioxetine produced small differences compared to placebo in the MADRS score, but only at a dose of 20 mg daily.  The degree of improvement does not compare favourably with similar studies using other antidepressants.  Rates of side effects, including sexual side effects, were higher in the vortioxetine groups compared to the placebo groups."   

A 2015 meta-analytic review paper by Rosenblat et al ( ) showed in general that antidepressants appear to help with cognitive function when used to treat depression.  But they conclude that "no statistically significant difference in cognitive effects was found when pooling results from head-to-head trials of SSRIs, SNRIs, TCAs, and NDRIs."

In this article by Llorca et al (2014), which is a "meta-regression analysis", it appears to favour vortioxetine as being better than other antidepressants.  ( article is then quoted elsewhere, such as on Wikipedia, as supporting the claim that vortioxetine is a superior antidepressant.  But the article shows indirect information only, there is no actual comparative study referred to at all.  And the findings, even from this study, really only show that vortioxetine is in the "same ballpark" in terms of effects, compared to other agents-- it certainly doesn't show superiority.

It was hoped that vortioxetine might help with generalized anxiety, but after several negative studies (, ), the latter of which showing that it was significantly inferior to another antidepressant (duloxetine), it is no longer claimed by anyone that it is an appropriate treatment for GAD.

Vortioxetine costs about $3.25 for a 20 mg dose.  This is about 10 times more than a 20 mg dose of citalopram.  

In conclusion, vortioxetine is another new option for treating depression.  It could be something to think about for treating anxious depression.  But there is no evidence that it is superior to other options, and is probably inferior in many cases.  There is no evidence of any specific benefit for treating anxiety disorders such as GAD.    I would consider it to be a third-line alternative at this point. 

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