Inflammatory markers and treatment outcome in treatment resistant depression: A systematic review

Background: A substantial percentage of depressed patients do not respond satisfactorily to conventional antidepressant treatment. This treatment resistant depression (TRD) may be partly related to inflammatory processes in the central nervous system. Accordingly, peripheral inflammatory markers might serve to predict treatment response with novel but still experimental forms of antidepressant treatment.

Methods: A literature search on treatment of TRD and inflammatory markers was performed using the PubMed/ Medline database on November 8th 2018, and 95 articles were retrieved initially, which were subsequently screened and selected only when the inclusion and exclusion criteria were met.

Results: Ten studies were recruited. In five studies higher baseline interleukin-6 (IL-6) or C-reactive protein (CRP)/high-sensitivity-CRP (hsCRP) in blood predicted better response to medication with anti-inflammatory characteristics, such as ketamine and infliximab. One study found that higher IL-6 predicted worse response to antidepressant treatment in patients with TRD. No evidence was found for the predictive value of other inflammatory markers (e.g., Tumor Necrosis Factor-alpha, Interferon-gamma).

Limitations: The number of available studies was limited; included studies showed considerable methodological variation and used different definitions for TRD.

Conclusion: The inflammatory markers IL-6 and CRP/hsCRP could hold promise as markers for the prediction of treatment response in TRD. Clearly, this field of research is still far from mature but it could pave the way for novel and efficacious treatments for at least the inflammatory type of TRD with more well-designed studies and more convincing results.