The Downstaging Concept in Treatment-Resistant Depression: Spotlight on Ketamine

Treatment-resistant depression affects about 30% of people with depression, and the likelihood of remission drops with each subsequent episode. This condition contributes heavily to global disease burden, raises morbidity and mortality, and lowers quality of life. It involves repeated difficult-to-treat episodes, with resistance growing over time. Staging captures how these changes lead to worsening treatment resistance and overall functioning. Ketamine, a rapid-acting antidepressant that can promote neuroplasticity, is argued here to be able to reverse this worsening process when used as an add-on treatment, offering hope and countering therapeutic nihilism.

Study at a glance

Abstract

Treatment-resistant depression is a pleomorphic phenomenon occurring in 30% of patients with depression. The chance to achieve remission decreases with every subsequent episode. It constitutes a significant part of the global disease burden, causes increased morbidity and mortality, and is associated with poor quality of life. It involves multiple difficult-to-treat episodes, with increasing resistance over time. The concept of staging captures the process of changes causing increasing treatment resistance and global worsening of functioning in all areas of life. Ketamine is a novel rapid-acting antidepressant with neuroplastic potential. Here, we argue that ketamine use as an add-on treatment of resistant major depressive disorder, based on its unique pharmacological properties, can reverse this process, give hope to patients, and prevent therapeutic nihilism.