Predictors and Risk Factors of Treatment-Resistant Depression: A Systematic Review

Objective: To systematically review the literature to identify and categorize the predictors and risk factors for treatment-resistant depression (TRD).

Data Sources: Online databases (PubMed, MEDLINE, Embase, and APA PsycNet) and relevant conference sources were searched from inception up to January 24, 2022. The following keywords were used: treatment-resistant depression, depressive disorder, predictors, risk, and biomarkers.

Study Selection: All studies that included a definition of TRD were included. A total of 1,686 abstracts were screened, and 57 studies were included in the final data synthesis.

Data Extraction: Data were extracted using a data extraction form developed for this study.

Results: The most frequently reported mental predictors/risk factors were greater symptom severity (9 studies), suicidality (8 studies), and recurrent depression (6 studies). Cardiovascular disease (4 studies), pain (3 studies), and thyroid dysfunction (3 studies) were the most common physical predictors/risk factors, while younger age (7 studies) and female gender (6 studies) were the most common demographic predictors/risk factors. Higher levels of neuroticism appeared twice in the literature. Several articles reported on genetic, biological, and imaging variables, but results were too heterogenous to identify common predictors/risk factors.

Conclusions: TRD is a complex disorder with many contributing factors that need to be identified and addressed earlier in the disease course to prevent its development or facilitate better treatment outcomes. Future work should focus on replicating the key predictors/risk factors identified in this review.