In the present systematic review, Salagre and colleagues examined evidence for the treatment of neurocognitive symptoms in depression, only including studies in their analysis that had explored changes in cognitive performance as primary or secondary outcomes in adults with diagnosed MDD. A total of 95 studies were identified, and a succinct overview of the evidence presented follows.

Effects of selective serotonin reuptake inhibitors (SSRIs) on cognition can be viewed conveniently through the lens of patient age: in the elderly, most of the studies failed to find significant effects of SSRIs on cognition; however, positive results in younger patients with MDD have been reported. Effects of serotoninergic-noradrenergic reuptake inhibitors (SNRIs) on cognition have been demonstrated in several studies. Improvements in cognitive performance in domains like executive function, verbal learning, attention, working memory, or verbal processing speed have been shown with duloxetine. Additionally, improvements driven by improved verbal learning and memory have also been shown in an elderly population (median age, 72 years; range 65-90 years) with duloxetine. Effects of vortioxetine, a serotonin modulator and stimulator (SMS), on cognition have been investigated in several studies. Vortioxetine is used to treat MDD. In addition, improvement of cognitive dysfunction in patients with unipolar major depression may be greater with vortioxetine than other antidepressants (eg, duloxetine), and this benefit may be independent of depressive symptom improvement. Vortioxetine appears to enhance serotonergic activity through inhibition of the reuptake of serotonin (5-HT), and it also has several other activities including 5-HT3 receptor antagonism and 5-HT1A-receptor agonism, although the contribution of these activities to the antidepressant effect of vortioxetine has not been established. Other pharmacologic activity with vortioxetine has also been described. The 5HT-7 antagonists include vortioxetine, lurasidone, and asenapine. There, too, it’s been an area more of preclinical than clinical interest, with the exception of vortioxetine. There are some data with vortioxetine showing ‒ presumably via 5-HT7, but we don’t know if that’s the case for sure ‒ that the molecule itself seems to exert a benefit on the Digit Symbol Substitution Test in attentional processing and psychomotor speed, independent of its effect on depression. 

A recent meta-analysis found that patients with moderate to severe MDD receiving vortioxetine 5-20 mg performed significantly better than the placebo or duloxetine groups, regardless of dosage, in tests assessing executive function and attention and also learning and memory. Improvements in cognition were accompanied by an improvement in functional capacity.

Vortioxetine seems to have a multi-domain beneficial effect on cognitive performance, and these effects seem to be independent of its effect on depressive symptoms. Ongoing clinical trials will provide further data on the effect of vortioxetine on cognition.