Vortioxetine Improves Processing Speed in Depression
In May 2018, the US Food and Drug Administration (FDA) approved a label change for the antidepressant vortioxetine (Trintellix), reflecting new data that show the drug can improve processing speed, an aspect of cognitive function that is often impaired in people with depression. Vortioxetine was first approved by the FDA for the treatment of depression in 2013.
The approval followed eight-week double-blind placebo-controlled studies of vortioxetine’s effects on cognitive function in adults aged 18–65 who have depression. The studies were known as FOCUS and CONNECT. Patients received either 10mg/day, 20mg/day, or placebo. Those who took vortioxetine showed improvement on the Digit Symbol Substitution Test, a measure of processing speed, in addition to improvement in their depression.
Editor’s Note: This is the first time the FDA has approved labeling that describes an antidepressant as improving aspects of cognition in depression. Cognition is impaired in many patients with depression, such that this component of the drug’s effects could be of clinical importance. Among the 5 serotonin (5HT) receptor effects of the drug (in addition to the traditional blockade of serotonin reuptake shared by all selective serotonin reuptake inhibitor antidepressants (SSRIs)), it is likely that vortioxetine’s effects in blocking 5HT-3 and 5HT-7 receptors are important to the drug’s effects on processing speed.
Antidepressant Brintellix Renamed Trintellix
A new label: Brintellix is now Trintellix.
You may notice the label on your prescription bottle changing. As of June, the antidepressant vortioxetine (formerly Brintellix) is now called Trintellix. The US Food and Drug Administration approved the change to reduce any possible confusion of the antidepressant with a blood-thinning medication called Brilinta.
More Evidence Vortioxetine Improves Depression and Cognitive Function
Vortioxetine (Brintellix) is a relatively new antidepressant that has a range of effects on serotonin receptors, making it different from selective serotonin reuptake inhibitors (SSRIs), which work only on the serotonin transporter. In multiple studies, it has treated not only depression but also cognitive dysfunction. In a new study led by Atul Mahableshwarkar and published in the journal Neuropsychopharmacology, 10–20 mg/day of vortioxetine reduced symptoms of depression more than placebo and improved performance on tests of cognitive ability more than placebo and another antidepressant, duloxetine.
While depression is often accompanied by cognitive dysfunction, in this study vortioxetine seemed to directly treat the cognitive deficits rather than reducing them by alleviating the depression. The participants were aged 18–65.
New Data on Vortioxetine for Cognition in Unipolar Depression
A 5mg dose of the antidepressant vortioxetine (Brintellix) was previously reported to have positive cognitive effects in elderly depressed patients. In a 2014 article in the International Journal of Neuropsychopharmacology, researcher Roger S. McIntyre et al. presented data from FOCUS, a study of cognition in depressed patients. The eight-week double-blind study included 18- to 65-year-olds (who were not selected for having cognitive problems per se).
McIntyre and colleagues used two tests of cognition, the Digit Symbol Substitution Test (DSST), which measures attention, psychomotor speed, and executive function, and the Rey Auditory Verbal Learning Test (RAVLT), which measures memory and acute and delayed recall. The researchers found that both the 195 patients taking 10mg/day of vortioxetine and the 207 patients taking 20mg/day of vortioxetine had better performance on both tests than the 196 patients who received placebo.
Response rates (meaning a patient achieved a 50% improvement on a scale of depression) were 47.7% on 10mg of vortioxetine, and 58.8% on 20mg of vortioxetine, compared to 29.4% on placebo. Remission rates were 29.5% on 10mg of vortioxetine and 38.2% on 20mg of vortioxetine versus 17% on placebo. McIntyre suggested that the drug worked both directly and indirectly, improving depression in some, but also improving cognition even in those whose depression did not improve.
The mechanism that could account for vortioxetine’s cognitive effects has not yet been identified. Like other selective serotonin reuptake inhibitor (SSRI) antidepressants, vortioxetine is a potent blocker of serotonin (5HT) reuptake, which it does by inhibiting the serotonin transporter (5HT-T). Unlike other SSRIs, vortioxetine is also a blocker of 5HT3 and 5HT7 receptors, an agonist at 5HT1A and 5HT1B and a partial agonist at 5HT1D receptors. It could be considered a polymodal 5HT active drug in contrast to the more selectively active 5HT-T–inhibiting SSRIs.
New Antidepressant Vortioxetine May Improve Cognition and Treatment-Resistant Depression
Vortioxetine (Brintellix) is a new antidepressant that has a range of effects on serotonin receptors, making it different from selective serotonin reuptake inhibitors (SSRIs), the most common type of antidepressants, which work only on the serotonin transporter. Researcher Johan Areberg et al. reported at the 2014 meeting of the American Psychiatric Association that the drug is an antagonist at receptors 5-HT3, 5-HT7, and 5-HT1D; a partial agonist at 5-HT1B; a full agonist at 5-HT1A; and an inhibitor of the 5-HT transporter. The researchers suggested that at doses of 5mg/day, vortioxetine occupies the 5-HT3 receptors and 50% of the serotonin transporter. As dosage increases to 20mg/day, vortioxetine is believed to occupy all of the serotonin targets at clinically relevant levels. Doses of 20mg/day were found to be effective in nine studies. Researcher Gennady Smagin et al. also reported that vortioxetine activates central histamine receptors.
Vortioxetine appears to be useful in patients who have previously failed to respond to antidepressants. Researcher George I. Papakostas et al. reported that in a cohort of about 500 patients who responded inadequately to previous prescriptions of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), the 252 taking vortioxetine improved more than the 241 taking the antidepressant agomelatine.
Editor’s Note: Vortioxetine’s superior effects are impressive, as agomelatine, which is approved for use in at least 41 countries including the UK, Canada, and Australia, but is not available in the US, has previously been shown to be more effective than a number of SSRIs in head-to-head comparisons. Agomelatine improves sleep and circadian rhythms via its dual effects as an agonist at melatonin M1 and M2 receptors and an inhibitor of 5HT2C receptors, which results in the release of norepinephrine and dopamine in the frontal cortex.
Vortioxetine may be unique among antidepressants in that it appears to improve cognition. Researcher John E. Harrison et al. reported that patients saw increases in executive function, attention, speed of processing, and memory while taking vortioxetine. This is consistent with studies in aged mice, whose cognition improves more on vortioxetine than on the SSRI fluoxetine, according to researcher Yan Li and colleagues.
