Souery et al reported criteria for chronic resistant (refractory) depression (CRD). This identifies a group of patients who can be extremely challenging to manage. The authors are from multiple universities in Europe, North America and Israel.

Classes of antidepressant therapies:

(1) tricyclic antidepressants (TCA)

(2) monoamine oxidase inhibitors (MAO inhibitors)

(3) selective serotonin reuptake inhibitors (SSRI)

(4) serotonin-norepinephrine reuptake inhibitors (SNRI)

(5) "other"

(6) electroconvulsive therapy (ECT)


Antidepressant therapy may be supplemented by augmentation therapy, which may include other medications such as lithium or antipsychotic agents.


A nonresponder to a class of antidepressants - failure to respond to:

(1) an adequate trial (dose, etc)

(2) lasting at least 6-8 weeks


A person who fails one class is typically switched to another antidepressant, usually from a different class.


Treatment resistant depression is defined as failure to respond to 2 or more antidepressant trials with adequate dose and duration. This may be classified based on the number of adequate trials that have failed.


Chronic resistant depression (CRD) is failure to respond after 12 months to several antidepressant trials with adequate dose and duration. Therapy will usually include augmentation therapy. If a standard regimens are used, then this corresponds to failure to respond to 6 trials to different antidepressants.

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