Major depressive disorder is a serious mental health disorder of high prevalence and the leading cause of disability worldwide. While there are several classes of therapeutic agents with proven antidepressant efficacy, only about 40–60% of patients respond to initial antidepressant monotherapy, and 30–40% of patients may even show resistance to treatment even under optimal antidepressant pharmacotherapy. Despite the existence of international guidelines, there are still no clear and widely accepted treatment algorithms, no established predictive biomarkers of response to treatment, while the management treatment- resistant depression is usually based on clinical experience. The present article offers a brief narrative review of studies published so far on the predictive quality of various blood-based peripheral biomarkers with respect to response to pharmacological, stimulation or behavioral treatment in patients with treatment-resistant depression. To summarize the results, there does not yet appear to be any specific biomarker that has sufficient discriminative predictive validity and can be used in the routine clinical practice of treating resistant depression. Many factors are likely to account for the above-mentioned research findings, including the wide variety of treatment protocols and the non-uniformly accepted definition of resistant depression used by the various studies, the small number of patients with treatment-resistant depression included, and the existence of different pathophysiological phenotypes of the disorder. The ineffective treatment of major depressive disorder requires an immediate improvement of our therapeutic approach by establishing clinically useful and easily accessible predictive biomarkers of response with high accuracy. The discovery of new and better clinical characterization of known biomarkers in the treatment of treatment-resistant depression could support a better staging and classification of the disorder, the development of personalized treatment algorithms for specific patient subgroups, the achievement of higher rates of stable remission, and the development of new precision drugs with minimal side effects.

ΚΕΥWORDS: Major depressive disorder, treatment-resistant depression, antidepressants, biomarkers, treatment response.

Agorastos Agorastos, Theano Gkesoglou, Anastasios Kleidonopoulos, Vasilios P. Bozikas

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