Treatment Resistant Depression— Advances in Somatic Therapies

University Health Network and University of Toronto, Toronto, Ontario, Canada.
Annals of Clinical Psychiatry (Impact Factor: 2.36). 10/2007; 19(4):279-87. DOI: 10.1080/10401230701675222
Source: PubMed


The failure to achieve remission for patients with Major Depressive Disorder (MDD) represents a major public health concern. Inadequately treated depression is associated with higher rates of relapse, poorer quality of life, deleterious personal and societal economic ramifications, as well as increased mortality rates. Unfortunately, only a minority of patients achieves this goal with initial antidepressant treatment and by convention, failure to achieve response after two adequate trials of antidepressant therapy defines "Treatment Resistant Depression" (TRD). Furthermore, results from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) group of studies suggest that approximately 50% of "real world" patients who meet criteria for MDD fail to achieve remission, even after four carefully monitored sequenced treatments.
Given these limitations of existing antidepressant medications alone and in combination, together with improved understanding of the neural circuitry of depression, it is not surprising that there is a renewed interest in neuromodulation strategies for TRD.
The purpose of this article is to review the evidence for the inclusion of various non-pharmacological, neuromodulatory strategies for TRD. Specifically, information regarding the mechanism, tolerability and efficacy of electroconvulsive therapy (ECT), magnetic seizure therapy (MST), repetitive transcranial magnetic stimulation (rTMS), vagal nerve stimulation (VNS), and deep brain stimulation (DBS) in ameliorating TRD will be presented.
Although these treatments are at various stages of clinical development, they represent a new frontier in expanding the treatment options available for individuals with TRD, as well as contributing to a better understanding the neurobiology of depressive disorders.

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    • "ECT is used in treatment resistant depression, which has been defined in several ways, but the generally accepted definition is failure to respond to successive adequate trials (dose and duration) of two antidepressants from different classes. Although initially it was estimated that 15-20% of patients with depression fall into the category of treatment resistant depression, the STAR-D naturalistic trial showed a rate as high as 50 % [16]. In treatment resistant depression, ECT provides fair efficacy and can help more than half of these patients [17] [18] [19] [20] [21]. "

    Electroconvulsive Therapy: Clinical Uses, Efficacy and Long-Term Health Effects, Edited by Kathleen Braddock, 08/2014: chapter An Evidence-Informed Model for the Modern Practice of Electroconvulsive Therapy; NOVA scientific publisher., ISBN: 978-1-63463-038-2
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    • "It is also important to develop a standardized, operational definition of TRD to facilitate comparisons across studies (McPherson et al., 2005). Although it was not the main aim of this research, this systematic review revealed, in line with many research studies (e.g., Bschor & Bauer, 2006; Catafau et al., 2001; Kennedy & Giacobbe, 2007; O'Reardon, Thase, & Papakostas , 2009), a considerable heterogeneity regarding most conceptual and methodological issues involved in the ascertainment of TRD in the published literature. More specifically , there are major differences in the number and type of previous failed trials required to make a diagnosis of TRD, the definition of treatment adequacy (dose, titration, and duration) and treatment response, and the assessment of primary and comorbid diagnoses. "
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    ABSTRACT: The objective of this research study was to assess pharmacological, somatic and/or psychological treatments in adults with a diagnosis of major depressive disorder who have not responded to at least one course of antidepressant medication. We conducted a systematic review to identify systematic scientific reviews and meta-analyses on treatment-resistant depression (TRD) published until February 2012. Of the sixty studies selected, sixteen met the inclusion criteria and were therefore included in the review. We considered eight main themes, including the definition of TRD, long-term results, and different treatment strategies, including so-called somatic therapies. Based on the review, the definition of TRD should be standardized in order to achieve a shared conceptualization of this disorder. This would allow a better understanding among clinicians and researchers in the field, promoting a homogeneous research methodology and thus leading to more reliable and comparable results. This essential conceptual clarification would also have a positive impact on patients with TRD, their families, and social and health systems.
    International Journal of Clinical and Health Psychology 05/2014; 14(2):145-153. DOI:10.1016/S1697-2600(14)70048-1 · 2.79 Impact Factor
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    • "DRL rats were resistant to treatment with two antidepressant drugs but effectively responded to ECS, which also increased BDNF levels specifically in the dorsal hippocampus, as was demonstrated in previous studies (Nibuya et al., 1995; Altar et al., 2004). In humans, approximately 30% of MDD patients do not respond adequately to standard medications (Shelton et al., 2010), whereas 80% of these 'medication-resistant' MDD patients do respond to ECT (Kennedy and Giacobbe, 2007). It is therefore possible that DRL is a generally 'medication-resistant' line. "
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    ABSTRACT: Major depressive disorder (MDD) is a common and devastating mental illness behaviorally characterized by various symptoms, including reduced motivation, anhedonia and psychomotor retardation. Although the etiology of MDD is still obscure, a genetic predisposition appears to play an important role. Here we used, for the first time, a multifactorial selective breeding procedure to generate a distinct 'depressed' rat line (DRL); our selection was based upon mobility in the forced swim test, sucrose preference and home-cage locomotion, three widely used tests associated with core characteristics of MDD. Other behavioral effects of the selection process, as well as changes in brain-derived neurotrophic factor (BDNF) and the response to three antidepressant treatments, were also examined. We show that decreased mobility in the forced swim test and decreased sucrose preference (two directly selected traits), as well as decreased exploration in the open field test (an indirectly selected trait), are hereditary components in DRL rats. In addition, lower BDNF levels are observed in the dorsal hippocampus of DRL rats, complying with the neurotrophic hypothesis of depression. Finally, electroconvulsive shocks (ECS) but not pharmacological treatment normalizes both the depressive-like behavioral impairments and the BDNF-related molecular alterations in DRL rats, highlighting the need for robust treatment when the disease is inherited and not necessarily triggered by salient chronic stress. We therefore provide a novel multifactorial genetic rat model for depression-related behaviors. The model can be used to further study the etiology of the disease and suggest molecular correlates and possible treatments for the disease.
    The International Journal of Neuropsychopharmacology 02/2014; 17(06):1-11. DOI:10.1017/S1461145714000030 · 4.01 Impact Factor
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