Monoaminergic‐based Pharmacotherapy for Depression

Abstract

Although recent advances in neuropharmacology, neuroendocrinology, molecular biology, and pharmacogenetics have been instrumental in bringing about potential treatments for depression which are fundamentally unrelated to their predecessors, including substance P antagonists, glutaminergic agents, and corticotropinreleasing factor (CRF) antagonists, nevertheless it was agents that influenced the function of monoamine receptors and transporters that were discovered initially by serendipity and then developed as treatments for depression. The development of such compounds also served as a framework for the understanding of depression as a medical illness affecting brain functioning. As a result of these efforts, our field has gained further understanding of the role of monoamines in depression. In previous chapters, the relevance of monoamines in the underlying pathophysiology of depression was reviewed. In the following chapter we will focus on describing the contemporary role of monoaminergic agents in the treatment of depression. 6.

Two Chronic Stress Models Based on Movement Restriction in Rats Respond Selectively to Antidepressant Drugs: Aldolase C As a Potential Biomarker

“…Antidepressant compounds act by selectively inhibiting the uptake of 5-hydroxytryptamine (selective serotonin reuptake inhibitors [SSRIs]), such as fluoxetine, or noradenaline (selective noradrenaline reuptake inhibitors [NRIs]), such as reboxetine from the synaptic cleft. Additional classes of antidepressants are monoamine oxidase inhibitors, dual serotonin and noradrenaline reuptake inhibitors, serotonin and dopamine reuptake inhibitors, or atypical antidepressants, all of which require chronic administration to be therapeutically effective ( Papakostas and Fava, 2005 ). However, only less than one-third of patients respond to the first drug prescribed.…”

Ziprasidone Augmentation of Escitalopram for Major Depressive Disorder: Efficacy Results From a Randomized, Double-Blind, Placebo-Controlled Study

“…Despite the increase in the number of medications approved by the U.S. Food and Drug Administration (FDA) for use as monotherapy in patients with major depressive disorder, (1) many patients suffering from depression continue to remain symptomatic despite one or more treatment trials of adequate dose and duration. (2) As a result, achieving remission for many such patients often requires the use of adjunctive treatment strategies including antidepressant augmentation with a variety of pharmacologic and nonpharmacologic agents.…”

A meta-analysis of clinical trials comparing the serotonin (5HT)-2 receptor antagonists trazodone and nefazodone with selective serotonin reuptake inhibitors for the treatment of major depressive disorder

“…Unfortunately, however, many depressed patients continue to remain symptomatic despite several treatments [32]. in addition despite hundreds of clinical trials spanning over five and a half decades, known differences among available antidepressants are, generally, limited to aspects of safety and tolerability [25]. in line with this tradition, several double-blind, randomized studies published to date suggest no difference in the overall antidepressant efficacy between the following two major classes of antidepressants: agents which selectively inhibit the serotonin-2 (5HT2) receptor including trazodone and nefazodone with antidepressants which selectively inhibit the serotonin transporter and, thereby, inhibit the reuptake of serotonin (selective serotonin-reuptake inhibitors—SSRis) in major depressive disorder (MDD) [4,5,6,9,10,16,17,23,33].…”

“…The serendipitous discovery of the precursors of two of the major contemporary antidepressant families during the late 1950s, iproniazid for the monoamine oxidase inhibitors and imipramine for the tricyclic antidepressants (TCAs), has led to the subsequent development of numerous antidepressant compounds [25]. Unfortunately, however, many depressed patients continue to remain symptomatic despite several treatments [32].…”