The role of vortioxetine in treating depression is “unclear,” according to a new Cochrane Database System Review.

Koesters et al conducted a meta-analysis of 15 studies (7,746 participants). Seven were placebo-controlled, while eight studies compared vortioxetine to serotonin-norepinephrine reuptake inhibitors (SNRIs). They were unable to identify any study that compared vortioxetine to other classes of antidepressants (eg, selective serotonin reuptake inhibitors [SSRIs]).

The researchers found that vortioxetine “may be more effective than placebo” in three efficacy outcomes: response (Mantel-Haenszel RR 1.35, 95% CI 1.22 to 1.49; 14 studies, 6220 participants), remission (RR 1.32, 95% CI 1.15 to 1.53; 14 studies, 6220 participants) and depressive symptoms measured using the Montgomery-Åsberg Depression Scale (MADRS) (score range: 0 to 34; higher score means worse outcome: MD –2.94, 95% CI –4.07 to –1.80; 14 studies, 5566 participants). However, the quality of the evidence was “low” for response and remission and “very low” for depressive symptoms. Compared to placebo, more participants discontinued vortioxetine because of adverse effects (RR 1.41, 95% CI 1.09 to 1.81; 14 studies, 6220 participants) but fewer discontinued due to inefficacy (RR 0.56, 95% CI 0.34 to 0.90, P=0.02; 14 studies, 6220 participants).

“Very low-quality evidence” from eight studies found no clinical significance between vortioxetine and SNRIS as a class for response or remission (RR 0.91, 95% CI 0.82 to 1.00; 3159 participants and RR 0.89, 95% CI 0.77 to 1.03; 3155 participants, respectively).

When compared to individual antidepressants, vortioxetine may be less effective than duloxetine in terms of response rates and depressive symptoms scores and there were also no statistically significant differences, as compared to venlafaxine.

Vortioxetine was superior to SNRIs as a class, in terms of tolerability (RR 0.90, 95% CI 0.86 to 0.94; 8 studies, 3134 participants) and also superior to duloxetine (RR 0.89, 95% CI 0.84 to 0.95; 6 studies; 2376 participants). However, the researchers note, the sensitivity analysis “casts some doubts on this result, as only two studies used comparable dosing.”

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They conclude that vortioxetine “may be more effective than placebo in terms of response, remission and depressive symptoms, but the clinical relevance of these effects is uncertain.” Moreover, the quality of evidence to support these findings was “generally low” and there was no advantage for vortioxetine in comparison to SNRIs or duloxetine.

“Studies with direct comparisons to SSRIs are needed to address this gap and may be supplemented by network meta-analyses to define the role of vortioxetine in the treatment of depression,” they state.


Koesters M, Ostuzzi G, Guaiana G, Breilmann J, Barbui C. Vortioxetine for depression in adults. Cochrane Database Syst Rev. 2017 Jul 5;7:CD011520.  [Epub ahead of print]