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Review
. 2021 Apr;38(4):456-467.
doi: 10.1002/da.23135. Epub 2021 Feb 2.

Treatment-resistant major depressive disorder: Canadian expert consensus on definition and assessment

Yuri E Rybak  1 , Ka S P Lai  1 , Rajamannar Ramasubbu  2 , Fidel Vila-Rodriguez  3 , Daniel M Blumberger  4 , Peter Chan  3 , Nicholas Delva  5 , Peter Giacobbe  4 , Caroline Gosselin  3 , Sidney H Kennedy  4 , Hani Iskandar  6 , Shane McInerney  4 , Paula Ravitz  4 , Verinder Sharma  1 , Ari Zaretsky  4 , Amer M Burhan  7   8
Affiliations
Review

Treatment-resistant major depressive disorder: Canadian expert consensus on definition and assessment

Yuri E Rybak et al. Depress Anxiety. 2021 Apr.

Abstract

Background: Treatment-resistant depression (TRD) is a debilitating chronic mental illness that confers increased morbidity and mortality, decreases the quality of life, impairs occupational, social, and offspring development, and translates into increased costs on the healthcare system. The goal of this study is to reach an agreement on the concept, definition, staging model, and assessment of TRD.

Methods: This study involved a review of the literature and a modified Delphi process for consensus agreement. The Appraisal of Guidelines for Research & Evaluation II guidelines were followed for the literature appraisal. Literature was assessed for quality and strength of evidence using the grading, assessment, development, and evaluations system. Canadian national experts in depression were invited for the modified Delphi process based on their prior clinical and research expertize. Survey items were considered to have reached a consensus if 80% or more of the experts supported the statement.

Results: Fourteen Canadian experts were recruited for three rounds of surveys to reach a consensus on a total of 27 items. Experts agreed that a dimensional definition for treatment resistance was a useful concept to describe the heterogeneity of this illness. The use of staging models and clinical scales was recommended in evaluating depression. Risk factors and comorbidities were identified as potential predictors for treatment resistance.

Conclusions: TRD is a meaningful concept both for clinical practice and research. An operational definition for TRD will allow for opportunities to improve the validity of predictors and therapeutic options for these patients.

Keywords: Canada; comorbidity; consensus; depression; depressive disorder; major depressive disorder; risk factors; treatment resistant.

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Conflict of interest statement

The authors declare that there are no conflict of interests.

Figures

Figure 1
Figure 1
Modified Delphi methodology. Three rounds of surveys were conducted to reach a consensus on a total of 27 items. Items that were reformulated may have been summarized into a single item or reworded as multiple items for improved clarity. *Grip strength, neuroticism, personality traits, social inhibition, body mass index, age, height, and biomarkers questions were excluded given low approval ratings by experts and lack of current literature support. HAM‐D‐24 was excluded given preference for the HAM‐D‐17. #Items #2–4 (melancholic features, atypical features, number of stressful life events), #6–14 (various depression and comorbidity scales), #18 (having both dichotomous and dimensional definitions), and #22 (definition to include psychotherapy) were excluded given low approval ratings by experts. &Items #2 and #3 (recommendation of a clinical staging tool) were excluded given low approval ratings by experts. HAM‐D, Hamilton depression rating scale
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