To the Editor We read with interest about the phase 2 randomized clinical trial by Daly et al1 that evaluated the efficacy and safety of intranasal esketamine as an adjunctive treatment for patients with treatment-resistant depression (TRD) during 130 days.1 We compliment the authors for a robust methodology. However, we feel that the findings of the article must be interpreted in light of certain facts that they have left unanswered. First, the authors defined TRD on the basis of failure of 2 trials of antidepressants, 1 of which was for the current episode. This definition is surprising to us, considering the generally accepted definition of TRD is failure of 2 antidepressant trials for the current episode.2 Elaborating further on this issue, going by the definition provided by the authors suggests that a patient who has treatment resistance for a particular episode would be considered to have TRD in their lifetime, as is considered for schizophrenia. However, it is important to understand that for schizophrenia, the concept of treatment resistance emerged in the background of the fact that clinicians wanted to use clozapine in a subgroup of patients. However, this is not the case with depression. In fact, in the context of depression, TRD is understood more from the perspective of reevaluation of diagnosis and possible causes that have been missed, rather than using certain specific treatment. The reported trial included about two-thirds of patients who had failed only a single trial of antidepressants. Accordingly, the claim of the authors that they included patients with TRD is not totally true.
Shouan A, Grover S. Adjunctive Intranasal Esketamine in Treatment-Resistant Depression. JAMA Psychiatry. Published online May 02, 2018. doi:10.1001/jamapsychiatry.2018.0690
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