Treatment resistant depression: methodological overview and operational criteria

A wide variety of definitions are used for Treatment Resistant Depression ( TRD), considering various criteria and different concepts. Some of the key issues are: the diagnosis, the treatment adequacy in terms of dose and dura tion, the treatment response assessment and the number of failed therapeuti c trials required. Systematic research has been characterizing the concept and criteria to define the different variables involved. Lack of consensus on these issues limits comparison across clinical trials and interpretation of treatment efficacy in the management of treatment resistant patients. T hrough reanalyzes of available data, we point out the limits of TRD definit ions and propose conceptual and operational criteria for a collaborative re search project on TRD. It appears that a number of variables commonly assoc iated to treatment resistance are independent of patients characteristics a nd mainly refer to misdiagnosis and inadequate treatment. The proposed crit eria are intended for therapeutic trials in TRD, combining the evaluation o f treatment efficiency and the validation of the concept of TRD itself. Maj or depression with poor response to two adequate trials of different classe s of antidepressants is proposed for an operational definition of TRD. Rati onale for this definition is discussed in contrast to alternative definitio ns. (C) 1999 Published by Elsevier Science B.V./ECNP.