6 Different Definitions of Treatment Resistant Depression

  • Failure to respond to 1 adequate trial of an antidepressant
  • Failure to respond to one or more adequate trials of antidepressants
  • Failure to respond to 2 adequate trials of antidepressants
  • Failure to respond to 2 adequate trials of antidepressants form different classes (e.g. SSRI and TCA)
  • Failure to respond to 2 or more adequate antidepressant trials
  • Failure to respond to 2 or more adequate antidepressants from different classes

Some authors and researchers object to the phrase failure to respond. They find this phrase blaming the patient. It is not the patients fault an antidepressant isn’t working or not working enough. Most of these researchers are authors of ECT publications. ECT is sometimes used as the last treatment option if antidepressants have failed. They prefer: pharmacotherapy treatment failure.

These six definitions were found in a systematic review of all randomized controlled trials on somatic treatment of treatment resistant depression. They found 233 references of which only 47 were RCT’s with unipolar depressed patients older than 18 years published in peer reviewed English Journals. Mostly publications about TRD is expert opinion on the subject. This publication is a systematic review.

In the majority of papers the information on the type of assessment for antidepressant resistance was not available. Two studies used a prospective assessment off TRD, 7 were retrospective assessed.

The majority of studies did not provide the maximum dose required to describe a previous treatment as a failure or success. 18 studies did not present information regarding requirements for prior treatment length.

Most studies did not use a thorough diagnostic evaluation, ideally performed with the use of a structured clinical interview, in case of treatment resistance.

A wide variety of terms has been used to decsribe TRD:

  • treatment-resistant
  • treatment-refractory
  • therapy-resistant

There is still an absence of definitive consensus about a general suitable definition for TRD. There is also a lack of how to assess the presence of TRD.
So what needs done is an international consensus about what is TRD and how should we assess it.


There is a clear need for an internationally shared framework of concepts and methods for the investigation of TRD that could reduce current idiosyncrasies and provide a reference system. Such a foundation is essential for the interpretation of research findings and for their translation to clinical practice.

What are your thoughts about this subject, do you use a definition?

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BERLIM, M., TURECKI, G. (2007). What is the meaning of treatment resistant/refractory major depression (TRD)? A systematic review of current randomized trials☆. European Neuropsychopharmacology, 17(11), 696-707. DOI: 10.1016/j.euroneuro.2007.03.009