How does Viibryd work as an antidepressant


Active ingredients

Tricyclic Antidepressants (TCAs)

After the discovery of the antidepressant effect of TCA, this class of substances quickly became the most widely used class of drugs for the treatment of depression. Soon, however, other drugs were developed to more selectively inhibit serotonin and norepinephrine reuptake and thus reduce anticholinergic side effects. TZA block muscarinic acetylcholine and histamine receptors as well as α even in therapeutic doses1-Adrenoreceptors and therefore lead to side effects such as dry mouth, constipation, sleep disorders and hypotonic circulatory disorders. Even small overdoses can be cardiotoxic and cause arrhythmias.

Selective Serotonin Reuptake Inhibitors (SSRI)

National and international guidelines therefore recommend the use of selective serotonin reuptake inhibitors (SSRIs) as the first treatment for major depression. The SSRIs such as citalopram, escitalopram, fluoxetine, fluvoxamine and paroxetine have a selective inhibitory effect on serotonin reuptake in therapeutic doses.

Selective norepinephrine reuptake inhibitors

Other selective monoamine reuptake inhibitors are the selective norepinephrine reuptake inhibitors (SNRI) such as z. B. reboxetine. However, in some meta-analyzes, reboxetine appears to be less effective than SSRIs, and these results could be due to its relatively poor tolerability.

Selective norepinephrine / dopamine reuptake inhibitors (SNDRI)

Another active ingredient is bupropion, which inhibits the reuptake of norepinephrine and dopamine.

Selective serotonin / norepinephrine reuptake inhibitors (SSNRIs)

The SSNRI such as B. Venlafaxine, Duloxetine and Milnacipran have a dual mode of action and inhibit the uptake of the neurotransmitters serotonin and norepinephrine.

Serotonin reuptake inhibitors and partial agonism

Recent developments have led to drugs that block serotonin reuptake while affecting a variety of 5-hydroxytryptamine (5-HT) receptor subtypes. For example, vilazodone has partial agonist activity at the 5-HT1A receptor, whereas vortioxetine binds to several other 5-HT receptor subtypes (5-HT1A, 5-HT1B, 5-HT1D, 5-HT3 and 5-HT7). However, it is not entirely clear whether these drugs have advantages over the SSRIs.

Noradrenergic and specifically serotonergic antidepressants (NaSSA)

Also, some antidepressants do not work by blocking the reuptake of norepinephrine and serotonin. An example of this is the tetracyclic compound mirtazapine, the α2-Blocks adrenoceptors causing the release of norepinephrine. Mirtazapine also blocks 5-HT2A and 5-HT2C receptors and thus increases the release of norepinephrine and dopamine in cortical regions. A similar antagonistic effect on 5-HT2C receptors has been proposed for the active ingredient agomelatine. It is questionable whether agomelatine blocks 5-HT2C receptors in clinical doses.

Monoamine oxidase inhibitors (MAOIs)

MAOIs inhibit the monoamine oxidase enzymes. A distinction is made between monoamine oxidase-A (MAO-A) and monoamine oxidase-B (MAO-B), which break down monoamines by deamination to the corresponding aldehydes, ammonia and hydrogen peroxide. By inhibiting these enzymes, the breakdown of serotonin, noradrenaline and dopamine is inhibited. The MAO inhibitors can be divided into selective, nonselective and reversible or irreversible inhibitors.
Examples of MAOIs are:


St. John's wort (Hypericum perforatum) extracts have been shown to be effective in the treatment of mild to moderate depression in clinical studies. Their use makes sense above all because the inhibition threshold of the patients towards herbal medicinal products seems to be lower than towards synthetic active ingredients.

Fast acting antidepressants

It has been shown that a single dose of the anesthetic ketamine, a non-competitive NMDA antagonist (N-methyl-D-aspartate), produces a rapid antidepressant effect within hours. The active ingredient produces this effect even in patients who have not responded to two or more typical antidepressants (e.g. SSRI or SNRI). Ketamine generates a paradoxical increase in extracellular glutamate in the medial prefrontal cortex and leads to an activity-dependent release of BDNF (brain-derived neurotrophic factor, a nerve growth factor), which could be the cause of the rapid synaptogenic response.
The activity-dependent BDNF release distinguishes ketamine from the typical antidepressants, which only slowly increase BDNF expression, but not BDNF release.

In the USA, a nasal spray containing esketamine has been approved for the treatment of major depression in combination with an SSRI or SNRI since March 2019 if the patient has not responded to at least two different antidepressant therapies in a current episode.