Treatment-resistant depression (TRD) is major depressive disorder in which an affected person does not respond adequately to at least two different antidepressant medications at an adequate dose and for an adequate duration.[1] Inadequate response has most commonly been defined as less than 25% reduction in depressive symptoms following treatment with an antidepressant.[2] Many clinicians and researchers question the construct validity and clinical utility of treatment-resistant depression as currently conceptualized.[3][4]
Other factors that may contribute to inadequate treatment are: a history of repeated or severe adverse childhood experiences, early discontinuation of treatment, failure to consider psychotherapy and other psychosocial interventions, patient noncompliance, misdiagnosis, cognitive impairment, low income and other social determinants, and concurrent medical conditions, including comorbidpsychiatric disorders.[2] Cases of treatment-resistant depression may also be referred to by which medications people are resistant to (e.g.: SSRI-resistant).[5] Adding further treatments such as aripiprazole or quetiapine is weakly supported as of 2022.[6]
^Wijeratne C, Sachdev P (September 2008). "Treatment-resistant depression: critique of current approaches". The Australian and New Zealand Journal of Psychiatry. 42 (9): 751–762. doi:10.1080/00048670802277206. PMID18696279. S2CID2848646.
^Rost, Felicitas; Booker, Thomas; Gonsard, Aneliya; de Felice, Giulio; Asseburg, Lorena; Malda-Castillo, Javier; Koutoufa, Iakovina; Ridsdale, Hannah; Johnson, Rebecca; Taylor, David; Fonagy, Peter (2024). "The complexity of treatment-resistant depression: A data-driven approach". Journal of Affective Disorders. 358: 292–301. doi:10.1016/j.jad.2024.04.093. Our findings reveal a complex and multifaceted condition and call for an urgent reconceptualization of TRD, which encompasses many interdependent variables and experiences.