Staging Treatment Intensity and Defining Resistant Depression: Historical Overview and Future Directions

Objective: To review existing staging models and definitions of treatment-resistant depression (TRD) and offer future directions within the context of up-to-date evidence.

Data Sources: A PubMed search was conducted on February 25, 2018, for articles in English on TRD staging or definition using the following keywords: depressive disorder, treatment-resistant OR treatment resistant depression cross-referenced with staging OR degree OR level OR definition. Relevant cross-references from identified articles were also included.

Study Selection: A total of 18 articles were identified that included a proposed TRD staging model, a proposed TRD definition, empirical work to support a model or definition, or any combination thereof.

Data Extraction: Included articles were summarized in chronological order in terms of the date the TRD staging model (and accompanying TRD definition if applicable) was first proposed. Findings from validation studies pertaining to staging or definition were then synthesized.

Results: Five staging models were identified. Strengths identified across staging models include rigorous assessment of adequacy of treatment, differentiation of resistance versus symptom return, assignment of equal weights to different pharmacotherapies, and accounting for augmentation. Future considerations should include differential weighting to specific augmentation agents based on available evidence, added weight to electroconvulsive therapy and ketamine treatments, and the addition of evidence-based psychotherapies. Dichotomous versus continuous approaches to TRD diagnosis were considered, with the latter (beginning with 1 failed trial) best explaining available data from large trials.

Conclusions: The most up-to-date evidence in the literature should guide future research in the definition and staging of TRD.