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 . 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 . 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 . 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.
|Title of host publication||Major Depressive Disorder|
|Subtitle of host publication||Risk Factors, Characteristics and Treatment Options|
|Publisher||Nova Science Publishers, Inc.|
|Number of pages||20|
|Publication status||Published - 2017 Jan 1|
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