Treatment Resistant Depression— Advances in Somatic Therapies

University Health Network and University of Toronto, Toronto, Ontario, Canada.
Annals of Clinical Psychiatry (Impact Factor: 2.53). 10/2007; 19(4):279-87. DOI: 10.1080/10401230701675222
Source: PubMed

ABSTRACT 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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    • "Electroconvulsive therapy (ECT), a well-known and widely used neurostimulation technique frequently applied in major depression , is not only considered to be one of our most potent treatment modalities, yielding response rates 'unchallenged' to the classic treatment algorithms, the application has also the capacity to result in significant clinical responses within weeks. By using unilateral or bilateral bifrontal/bitemporal ECT, after 10 sessions performed two or three times a week or even less, in general 80–90% of the depressed patients clinically respond (Kennedy and Giacobbe, 2007). When including treatment resistant depressed patients (TRD), clinical success is reached in 50–70% (Rush and Contents lists available at ScienceDirect journal homepage: "
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    ABSTRACT: Major depression is a worldwide severe mental health problem. Unfortunately, not all depressed patients respond to pharmacotherapy or psychotherapy, even when adhering to treatment guidelines. Even though current guidelines do not in particular advocate repetitive Transcranial Magnetic Stimulation (rTMS) in refractory treatment resistant depression (TRD), using more intensive stimulation parameters might hold promise as a valuable alternative. Consequently, in this randomized sham-controlled crossover study, we wanted to evaluate clinical outcome of intensive HF-rTMS treatment in TRD when applied to the left dorsolateral prefrontal cortex (DLPFC). After a 2-week antidepressant washout, 20 unipolar TRD patients, at least stage III, received 20 sham-controlled high-frequency (HF)-rTMS sessions, in a crossover design. Five daily suprathreshold HF-rTMS sessions were spread over four successive days delivering in total 31,200 stimuli. Overall, the procedure resulted in immediate statistical significant decreases in depressive symptoms regardless of order/type of stimulation (real/sham), suggesting possible placebo responses. On the other hand, albeit only 35% (7/20) of the patients showed a 50% reduction of their initial Hamilton Depression rating score at the end of the two-week procedure, all these patients showed a prompt clinical response after real HF-rTMS treatment, not after sham. Furthermore, a shorter duration of the current depressive episode was a predictor for beneficial clinical outcome. Unresponsiveness to former ECT could be indicative for negative clinical outcome in these kinds of patients. Single center setup with relatively small sample size and no follow-up. Our findings indicate that intensive HF-rTMS treatment might have the potential to result in fast clinical response when confronted with a refractory TRD patient.
    Journal of Affective Disorders 07/2013; 151(2). DOI:10.1016/j.jad.2013.07.008 · 3.71 Impact Factor
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