The Complexity of Treatment-Resistant Depression: A Data-driven Approach

Rost, Felicitas; Booker, Thomas; Gonsard, Aneliya; de Felice, Giulio; Asseburg, Lorena; Malda-Castillo, Javier; Koutoufa, Iakovina; Ridsdale, Hannah; Johnson, Rebecca; Taylor, David and Fonagy, Peter (2024). The Complexity of Treatment-Resistant Depression: A Data-driven Approach. Journal of Affective Disorders, 358 pp. 292–301.



Background: Recent systematic reviews highlight great variability in defining and assessing treatment-resistant depression (TRD). A key problem is that definitions are consensus rather than data-led. This study seeks to offer a comprehensive socio-demographic and clinical description of a relevant sample.

Methods: As part of a pragmatic randomized controlled trial, patients (N = 129) were managed in primary care for persistent depression and diagnosed with TRD. Data included previous treatment attempts, characteristics of the depressive illness, functioning, co-occurring problems including suicidality, psychiatric and personality disorders, physical health conditions, and adverse events.

Results: Findings show a severe and chronic course of depression with a duration of illness of 25+ years. Overall, 82.9% had at least one other psychiatric diagnosis and 82.2% at least one personality disorder; 69.8% had significant musculoskeletal, gastrointestinal, genitourinary, or cardiovascular and respiratory physical health problems. All but 14 had severe difficulties in social and occupational functioning and reported severely impaired quality of life. Suicidal ideation was high: 44.9% had made at least one serious suicide attempt and several reported multiple attempts with 17.8% reporting a suicide attempt during childhood or adolescence. Of the patients, 79.8% reported at least one adverse childhood experience.

Limitations: Potential for recall bias, not examining possible interactions, and absence of a control group.

Conclusions: Our findings reveal a complex and multifaceted condition and call for an urgent reconceptualization of TRD, which encompasses many interdependent variables and experiences. Individuals with TRD may be at a serious disadvantage in terms of receiving adequate treatment.

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