Latest Update on the Mechanism of Action of Selective Serotonin Reuptake Inhibitors (SSRIs)

Time to read: 5 minutes

Over the past few decades, Selective Serotonin Reuptake Inhibitors (SSRIs) have become one of the most commonly prescribed medications to treat various mental health conditions, such as anxiety, depression, and obsessive-compulsive disorder (OCD).

Despite their widespread use, the exact mechanism of action of SSRIs has remained somewhat of a mystery.

In recent years, researchers have made great progress in uncovering the molecular pathways involved in SSRI action, providing valuable insight into their therapeutic effects.

In this article, we will discuss the latest updates on the mechanism of action of SSRIs, including how they interact with serotonin receptors, modulate neurotransmitter levels, and how they affect the brain’s reward system.

The serotonergic hypothesis of depression postulated that diminished activity of serotonin pathways plays a causal role in the pathophysiology of depression. This hypothesis led to the development of SSRIs and SNRIs in the treatment of depression.

However, the serotonergic hypothesis was not conclusively substantiated, and the pathogenesis of depression has moved beyond the simplistic serotonergic hypothesis of depression.

Both SSRIs and SNRIs are effective medications in the treatment of depression. [Cipriani Network Meta-analysis]

See Simplified guide on antidepressants and Guidelines on the management of depression. 

The hypothesis has now moved towards recognising the role of serotonin and its complex actions at cellular and molecular levels.

Serotonin synapses are present brain wide, and consist of 14 different receptor types which are encoded by seven gene families.

Here we describe the key postulated mechanisms of action of SSRIs.