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Can J Psychiatry. 2007 Jan;52(1):46-54.

Definition, assessment, and staging of treatment-resistant refractory major depression: a review of current concepts and methods.

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Depressive Disorders Program, Douglas Hospital Research Centre, McGill University, Montréal, Québec.



Up to 15% of depression patients eventually present with treatment-resistant or refractory depression (TRD), a condition that causes significant social and economic burdens. Our paper aims to summarize the current medical literature on the conceptual and methodologic issues involved in the definition, assessment, and staging of TRD.


We reviewed the recently published medical literature to identify papers that specifically discuss TRD. For this, we searched MEDLINE, EMBASE, and PsycINFO for potentially relevant English-language articles published between January 1996 and June 2006.


Recent methodologic and conceptual advances have contributed to the achievement of an acceptable level of theoretical consensus on the general meaning of TRD. Accordingly, depression is usually considered resistant or refractory when at least 2 trials with antidepressants from different pharmacologic classes (adequate in terms of dosage, duration, and compliance) fail to produce a significant clinical improvement. Regarding diagnostic assessments, an accurate and systematic evaluation should be made to elicit the potential role of several contributing factors, such as medical and psychiatric comorbidity.


Recently, 3 staging methods for TRD have been described, but they currently require extensive empirical support. Future research on TRD should include prospective studies addressing the validity of the proposed criteria, the impact of depression comorbid with other psychiatric disorders and (or) physical conditions, and the possible predictors o treatment outcome. There is an important and clear need for studies that empirically test current definitions, assessment strategies, and staging methods of TRD.

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