Treatment-resistant depression

Neurobiological etiology and pharmacological treatment strategies

Kyoung Sae Na, Kwang Yeon Choi, Yong Ku Kim

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Treatment strategies for treatment resistant depression (TRD) seek to overcome insufficient responses to monoaminergic antidepressants. Many of the currently available antidepressants work via mechanisms that modulate serotonin function. Initially, the serotonergic deficiency hypothesis was prominent in explaining antidepressant effects [1]. However, two key issues call the appropriateness of the serotonin-based hypothesis for the pathophysiology of depression and action of antidepressants into question. One issue is the time lag. Generally, it takes two to four weeks for antidepressants to exert their therapeutic effects [2]. The other issue is the low response rate, as was shown in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial [3, 4]. In the STAR*D trial, the remission rate for a first trial of antidepressants was approximately 30%. About one in four people who switched to another medication then felt better, regardless of the class of antidepressants. If a new, second medication was added to treatment with a first selective serotonin reuptake inhibitor (SSRI), approximately one in three patients saw improvement. In patients who failed to respond to a two-antidepressant treatment strategy, only one in seven patients saw improvement in a trial which added a third antidepressant. Finally, less than 70% of patients might be improved after four trials of antidepressants treatments during a 1-year period. The limited effectiveness of antidepressants in real-world clinical practice indicates the need for a treatment strategy for treatment-resistant depression (TRD). Currently, various factors, such as neuronal, glial, and synaptic dysfunctions, help to explain the pathophysiological mechanisms of TRD for which pharmacological approaches are needed [5]. One of the most promising pharmacological mechanisms is modulation of glutamatergic receptors, such as N-Methyl-D-aspartate (NMDA) and a-amino-3-hydroxy- 5-methyl-4-isoxazole propionic acid receptors (AMPAR). In this review, we discuss recently updated findings for the neurobiological mechanisms underlying TRD and possible pharmacological treatment strategies.

Original languageEnglish
Title of host publicationMajor Depressive Disorder
Subtitle of host publicationRisk Factors, Characteristics and Treatment Options
PublisherNova Science Publishers, Inc.
Pages237-256
Number of pages20
ISBN (Electronic)9781536120035
ISBN (Print)9781536119800
Publication statusPublished - 2017 Jan 1

Fingerprint

Treatment-Resistant Depressive Disorder
Antidepressive Agents
Pharmacology
Therapeutics
Depression
Serotonin
Isoxazoles
Serotonin Uptake Inhibitors
Therapeutic Uses
N-Methylaspartate
Neuroglia

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Na, K. S., Choi, K. Y., & Kim, Y. K. (2017). Treatment-resistant depression: Neurobiological etiology and pharmacological treatment strategies. In Major Depressive Disorder: Risk Factors, Characteristics and Treatment Options (pp. 237-256). Nova Science Publishers, Inc..

Treatment-resistant depression : Neurobiological etiology and pharmacological treatment strategies. / Na, Kyoung Sae; Choi, Kwang Yeon; Kim, Yong Ku.

Major Depressive Disorder: Risk Factors, Characteristics and Treatment Options. Nova Science Publishers, Inc., 2017. p. 237-256.

Research output: Chapter in Book/Report/Conference proceedingChapter

Na, KS, Choi, KY & Kim, YK 2017, Treatment-resistant depression: Neurobiological etiology and pharmacological treatment strategies. in Major Depressive Disorder: Risk Factors, Characteristics and Treatment Options. Nova Science Publishers, Inc., pp. 237-256.
Na KS, Choi KY, Kim YK. Treatment-resistant depression: Neurobiological etiology and pharmacological treatment strategies. In Major Depressive Disorder: Risk Factors, Characteristics and Treatment Options. Nova Science Publishers, Inc. 2017. p. 237-256
Na, Kyoung Sae ; Choi, Kwang Yeon ; Kim, Yong Ku. / Treatment-resistant depression : Neurobiological etiology and pharmacological treatment strategies. Major Depressive Disorder: Risk Factors, Characteristics and Treatment Options. Nova Science Publishers, Inc., 2017. pp. 237-256
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