Chapter 8 - Pharmacological Treatment of Major Depressive Disorder

Abstract

This chapter describes current and emerging evidence-based pharmacological treatments for major depressive disorder. Over the past 60years, antidepressants have primarily targeted the monoamine system, starting with the serendipitous discovery of monoamine oxidase inhibitors and tricyclic antidepressants. Numerous mechanistically dissimilar antidepressants targeting the monoamine system have now been developed. Selective serotonin reuptake inhibitors represent the most commonly prescribed antidepressants, with several other classes of antidepressants available with comparable efficacy and tolerability. Most recent advances in antidepressant drug development have targeted specific monoamine receptors, rather than only increasing monoamine levels. Targeting specific receptors has allowed for modest improvements in efficacy and tolerability, as well as novel benefits, such as procognitive effects produced by antagonism of 5HT7. Numerous nonmonoaminergic systems (e.g., glutamate, inflammation) are now being targeted with novel agents that may represent the next generation of antidepressants. Glutamate modulating agents, such as ketamine, show the most promise, demonstrating rapid and robust antidepressant effects.