Defining treatment‐resistant depression

Abstract

Background: Varying conceptualizations of treatment-resistant depression (TRD) have made translating research findings or systematic reviews into clinical practice guidelines challenging and inconsistent. Methods: We conducted a review for the Centers for Medicare & Medicaid Services and the Agency for Healthcare Research and Quality to clarify how experts and investigators have defined TRD and to review systematically how well this definition comports with TRD definitions in clinical trials through July 5, 2019. Results: We found that no consensus definition existed for TRD. The most common TRD definition for major depressive disorder required a minimum of two prior treatment failures and confirmation of prior adequate dose and duration. The most common TRD definition for bipolar disorder required one prior treatment failure. No clear consensus emerged on defining adequacy of either dose or duration. Our systematic review found that only 17% of intervention studies enrolled samples meeting the most frequently specified criteria for TRD. Depressive outcomes and clinical global impressions were commonly measured; functional impairment and quality-of-life tools were rarely used. Conclusions:Two key steps are critical to advancing TRD research: (a) Developing a consensus definition of TRD that addresses how best to specify the number of prior treatment failures and the adequacy of dose and duration; and (b) identifying a core package of outcome measures that can be applied in a standardized manner. Our recommendations about stronger approaches to designing and conducting TRD research will foster better evidence to translate into clearer guidelines for treating patients with this serious condition.

A prospective, multi-center randomized, controlled, blinded trial of vagus nerve stimulation for difficult to treat depression: A novel design for a novel treatment

“…These recommendations were based on a review of the evidence outlined in CAG-00313-R2 which included an expert Medicare Evidence Development and Coverage Advisory Committee (MEDCAC) panel convened on April 27, 2016, an external technology assessment conducted by the Agency for Healthcare Research and Quality (AHRQ) [17], and CMS internal review. Finally, other systematic literature reviews of VNS for patients with TRD also called for an RCT to establish clinically valuable antidepressant effects [18].…”

“…A significant subset (~15-20%) of patients do not respond to multiple antidepressant treatments and are referred variously to as "treatmentresistant depression" (TRD), "treatment-resistant major depression" (TRMD), or "difficult-to-treat depression" (DTD) [40]. Recent consensus indicates that failure to respond to two or more adequate doseduration antidepressant trials meets the minimal definition of TRD [18]. Historically, electroconvulsive therapy (ECT) has been the "gold standard" treatment for TRD [45].…”

Human induced pluripotent stem cells technology in treatment resistant depression: novel strategies and opportunities to unravel ketamine’s fast-acting antidepressant mechanisms

“…Because only one every six intervention studies enrol patients that meet these criteria, information on this population can be considered sparse. 63 True resistance to the effect of specific drugs might only play a minor part, 64 so deep phenotyping must include multiple strategies to address the persistence of depression in individual subjects when small-sample protocols are implemented. Within stratified samples of TRD patients, exceptional ketamine responders (eK-Rs) and ketamine non-responders (K-NRs) must be identified.…”

The Role of the Patient-Centered Medical Home in Treating Depression

“…While the PCMH is well positioned to provide a large proportion of depression treatment, the care of some patients can be challenging. One example is patients with treatment-resistant depression, which has been operationalized as a lack of response or remission following two or more adequate courses of treatment [90]. The literature on treatment-resistant depression is limited, with some support for antidepressant augmentation and adjunctive psychotherapy [91,92].…”