Vortioxetine: a next-generation antidepressant

Vortioxetine is a next-generation antidepressant with multimodal action. which was approved in 2013.

It is a novel antidepressant with a unique profile, since acts as a multimodal serotonergic agent. Its effectiveness in major depressive disorder has been established in short- and long-term studies.

Furthermore, its ability to modulate a wide range of neurotransmitters (serotonin, dopamine, norepinephrine, histamine, glutamate or GABA) confers procognitive effects to vortioxetine. On the other hand, the side effects also differ from conventional antidepressants, since It has a low incidence of sexual dysfunction, weight gain or cardiovascular disorders.

Major depressive disorder (MDD)

Major depressive disorder (MDD) affects the way people feel, think, and behave. Its main symptoms are persistent feelings of sadness and loss of interest in activities that the person previously enjoyed (anhedonia).

This mood disorder is often not recognized or treated, which can lead to tragic consequences, such as suicide and deterioration in interpersonal relationships.

Regarding its etiology, there are multiple factors, although at a general level it has been related to a combination of genetic, environmental, biological and physiological factors.

On the other hand, men and women experience the symptoms of depression differently. Women experience more feelings of guilt, sadness, and worthlessness, while men tend to be irritable, tired, and lose interest in activities that were previously pleasurable.

Pharmacological options for MDD

There are more than thirty pharmacotherapy options available for unipolar depression. Some of them are selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs) or serotonin-norepinephrine reuptake inhibitors (SNRIs).

There are also bupropion, serotonin reuptake antagonists/inhibitors, second-generation alpha antipsychotics, monoamine oxidase inhibitors (MAOIs), norepinephrine reuptake inhibitors, and tetracyclics.

The lack of response to available antidepressant treatments is one of the great challenges of psychiatry. Up to 1/3 of patients with major depressive disorder (MDD) do not achieve a complete response and even in patients in remission residual cognitive symptoms are observed.

Taking this need into account and thanks to the advance in knowledge of the neural circuits involved in MDD, More and more theories are emerging that want to explain depression beyond serotonergic activity..

The monoaminergic system, which includes the serotonergic, noradrenergic, and dopaminergic pathways, is widespread throughout the brain and its multiple interconnections are known to play an important role in mood disorders.

This more integrative concept has motivated the search for drugs that modulate the neurotransmitters involved in the regulation of the monoaminergic system, such as glutamate or γ-aminobutyric acid (GABA). And it is precisely from this interest that vortioxetine is developed.

Vortioxetine: multimodal action

Vortioxetine is an antidepressant with multimodal action, which gives it a unique profile. Its antidepressant effectiveness has been demonstrated in several studies.

This drug has a unique and complex mechanism of action. Like conventional selective serotonin reuptake inhibitors (SSRIs), can increase serotonin levels by inhibiting serotonin transporters (SERT).

However, its action on the different subtypes of 5HT receptors gives it characteristic properties and has led it to be considered a multimodal antidepressant. Furthermore, its ability to modulate several neurotransmitters (serotonin, dopamine, norepinephrine, histamine, glutamate and GABA) allows it to act on domains such as cognition.

On the other hand, Its adverse effect profile is different from that of other conventional antidepressants. This is because it is related to a low incidence of sexual dysfunction, weight gain or cardiovascular disorders.

The relationship between vortioxetine and cognition

Vortioxetine is a good alternative in the treatment of neurocognitive deficits in MDD, according to preclinical and clinical studies. This antidepressant improves learning difficulties and prevents stress-induced learning deficits.

There is a positive effect of vortioxetine on deficits in cognitive flexibility, one of the main cognitive symptoms in MDD. A positive effect on memory has also been observed, greater than with escitalopram or duloxetine.

Besides, Vortioxetine promotes neuroplasticity more quickly than other SSRIs. In clinical studies, vortioxetine has been shown to have no negative effects on cognition.

Analyzes indicate that this drug does not appear to act on a specific cognitive domain, but rather on a wide variety of domains and that it is most useful in patients who are actively employed.

Additionally, it appears to have a safer profile compared to other traditional antidepressants. However, nausea rates tended to be numerically higher in the vortioxetine trials. With efficacy and tolerability established in numerous clinical trials, Vortioxetine can be considered an alternative to other antidepressants on the market.

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