What are the Different Types of Antidepressants AND How Do They Work? | Mechanisms of Action

Posted on: May 6, 2022
Last Updated: November 24, 2023

Dr Sanil Rege covers the mechanisms of action of common antidepressants.

Antidepressants are medications that can help relieve symptoms of depression, social anxiety disorder, anxiety disorders, seasonal affective disorder, dysthymia, or mild chronic depression, as well as other conditions. Antidepressants were first developed in the 1950s. Their use has become progressively more common in the last 20 years. Not all antidepressants are the same. They differ in their mechanisms of action and side effect profiles.

SSRIs: SSRIs block Serotonin transporter (SERT) and therefore increase levels of serotonin in the synaptic cleft. This is thought to be linked to its anti-depressive effect. There are however other mechanisms recently discovered that may be playing a part.

SNRIs block the reabsorption (reuptake) of the neurotransmitters serotonin and norepinephrine in the brain by blocking SERT and norepinephrine/noradrenaline transporter (NART / NET).

Tricyclic Antidepressants (TCAs): TCAs block the reabsorption (reuptake) of the neurotransmitters serotonin, norepinephrine and dopamine by blocking SERT, NART and Dopamine transporter (DAT).

Recent evidence suggests that Antidepressants work by increasing levels of BDNF through their action on the TRKB (BDNF) receptor.

Monoamine Oxidase Inhibitors (MAOI) – MAOIs increase levels of Dopamine, Serotonin and Noradrenaline by blocking MAO-A and MAO-B enzymes which are responsible for the breakdown of dopamine, serotonin and noradrenaline.

NASSA (Mirtazapine, Mianserin) – Dual Effect – Serotonin Antagonism and increasing noradrenaline by alpha 2 antagonism.

Melatonergic agonists : Agomelatine

Serotonin modulators: Vortioxetine

NARI: e.g Reboxetine Acts as a reuptake inhibitor for the neurotransmitters norepinephrine (noradrenaline) and epinephrine (adrenaline) by blocking the action of the norepinephrine/noradrenaline transporter (NET).

NDRI (Noradrenaline and dopamine reuptake inhibitor): e.g Bupropion – They block the action of specific transporter proteins. NET and DAT- increasing the amount of active norepinephrine and dopamine neurotransmitters throughout the brain.

SARI (Serotonin antagonist and reuptake inhibitor) – Trazodone is an antidepressant that works by inhibiting both serotonin transporter and serotonin type 2 receptors.