A Comprehensive Monograph on Sertraline (DB01104)

I. Introduction and Executive Summary

Sertraline is a cornerstone therapeutic agent in modern psychopharmacology, classified as a selective serotonin reuptake inhibitor (SSRI).[1] First approved in the United States in 1991, it has become one of the most widely prescribed psychotropic medications globally, particularly in the U.S., where in 2016 it was the most commonly prescribed medication in its class.[4] This widespread use reflects a broad spectrum of clinical utility combined with an efficacy and tolerability profile that represented a significant advance over older classes of antidepressants.

The primary therapeutic effect of sertraline is achieved through its highly selective inhibition of the presynaptic serotonin transporter, which increases the synaptic concentration of the neurotransmitter serotonin.[5] This mechanism underpins its efficacy across a range of psychiatric conditions. The U.S. Food and Drug Administration (FDA) has approved sertraline for the treatment of major depressive disorder (MDD), obsessive-compulsive disorder (OCD) in both adult and pediatric populations, panic disorder (PD), post-traumatic stress disorder (PTSD), social anxiety disorder (SAD), and premenstrual dysphoric disorder (PMDD).[3]

A key factor in sertraline's clinical ascendancy is its favorable safety profile relative to older agents like the tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs). Sertraline is characterized by a relative lack of anticholinergic, antihistaminic, and cardiovascular side effects, which were common and often treatment-limiting with previous generations of antidepressants.[2] This improved tolerability has made it a first-line option for many of its approved indications.[7]