Vortioxetine: A Unique Antidepressant for Major Depressive Disorder

Vortioxetine: A Unique Antidepressant for Major Depressive Disorder
Vortioxetine: A Unique Antidepressant for Major Depressive Disorder
The antidepressant may improve cognition independent of its effect on other depression symptoms.

Major depressive disorder (MDD) causes symptoms that interfere with a person’s ability to work, sleep, eat, and think. Almost 7% of American adults experience MDD symptoms each year. Symptoms include sadness, helplessness, hopelessness, difficulty concentrating, memory lapses, and the inability to make decisions.1

Vortioxetine (Brintellix), a novel antidepressant, may effectively treat symptoms of depression and cognitive dysfunction in adults with MDD, results from a study published in the International Journal of Neuropsychopharmacology suggest. The findings indicate that depressive and cognitive symptoms may be mediated by different receptors and brain chemicals. Vortioxetine seems to work independently in both domains.2

“Vortioxetine differs from selective serotonin reuptake inhibitors [SSRIs] in its multimodal effect on serotonin transport and reuptake,” said study researcher Roger S. McIntyre, MD, FRCP, a professor of psychiatry at the University of Toronto in Ontario, Canada, and Psychiatry Advisor editorial board member.

“Vortioxetine may also affect a variety of other neurotransmitters. The relevance is that it’s the first antidepressant to affect the domain of cognition independently, a domain we struggle to treat well in depression.”

Vortioxetine received FDA approval for the treatment of major depressive disorder in 2013. The drug is an SSRI, but it also acts as a 5HT agonist, antagonist, and transport inhibitor.3

“We do not know exactly how vortioxetine mediates cognition, but it may be as a receptor antagonist at 5HT3 and 7, where it may impact neurotransmitters like glutamine and acetylcholine that are intimately involved in regulation of cognitive function,” said McIntyre.

The eight-week, double-blind, multinational study compared the efficacy of vortioxetine at 10mg and 20mg per day against placebo on both cognition and depression in 602 adults with MDD aged 18 to 65 years. Both doses of vortioxetine significantly improved cognition scores and depression symptoms compared with placebo.2

Through path and subgroup analysis, the researchers were able to show that vortioxetine’s effect on cognition was largely direct and independent of its effect on other symptoms of depression.2

“That is the zinger. There is little evidence that any other antidepressant improves cognition independent of its effect on depressive symptoms,” McIntyre said.

The most commonly reported negative side effects from vortioxetine were headache and nausea. There were no major safety concerns.2

Results of 2014 meta-analysis published in Psychopharmacology that assessed the efficacy and safety of vortioxetine found the SSRI was significantly more effective in treating MDD than placebo. Common adverse events included nausea, dizziness, headache, dry mouth, and diarrhea.4

Vortioxetine comes in once-daily tablets of 5mg, 10mg, 15mg, and 20 mg. Women who are or may become pregnant, or who are breastfeeding should use caution when taking this drug.

Dosages range from 5mg to 20mg, and are usually started low and increased gradually over several weeks. Physical symptoms of depression may start to improve within two weeks, but a full response may require 6 to 8 weeks of treatment  At present, vortioxetine is indicated only for the treatment of MDD.3

“Our findings may suggest an additional indication for a subpopulation of adults with MDD who have significant cognitive symptoms. Future research may find that this drug can be used to treat many other conditions besides depression that cause cognitive dysfunction,” concluded McIntyre.

Disclosure: Roger S. McIntyre, MD, has served as an advisor or consultant for Lundbeck, Inc., and is currently on or has served on the company’s speaker’s bureau. Vortioxetine is manufactured by Lundbeck and Takeda Pharmaceuticals America, Inc.

Chris Iliades, MD, is a freelance medical writer.

Medically reviewed by Pat F. Bass III, MD, MS, MPH.