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

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.

Ketamine as Add-On Treatment in Psychotic Treatment-Resistant Depression

“…This paper supports evidence for the distinct phenomenology of psychosis and dissociation that pose separate diagnostic entities. The idea of downstaging, which influences the course and prognosis of mood disorders, is consistent with psychotic TRD as determined by the disease's development stage and the ketamine effect found in the studied instances [31].…”

Inflammation and Treatment-Resistant Depression from Clinical to Animal Study: A Possible Link?

“…First, the rats were allowed to adapt to the sucrose solution (2% w / v ) by placing two bottles of sucrose solution in each cage for 24 h. Second, the rats were housed individually and one bottle of sucrose solution, each containing a specific volume (200 mL), was replaced with water. Sixty minutes later, sucrose consumption was measured as follows (sucrose preference = V (sucrose solution) / [V (sucrose solution) + V (water]) × 100%) [ 27 ].…”

Exploring the Relationship between Mood Disorders and Coexisting Health Conditions: The Focus on Nutraceuticals

“…Shielding against oxidative stress damage Pro-inflammatory cytokines reduction Neuroprotection Neurotransmitter modulation Lack of data 1-3 g daily 6 N-Acetyl Cysteine A compound arises from L-cysteine subjected to acetylation, recognized for its role as a precursor to glutathione regarded as antioxidant. It is often used as a medication to treat acetaminophen overdose.…”

“…The table presents a summary of the effects exerted by nutraceuticals on MDD and BD, considering the preparations and dosages. Information regarding the recommended use as an adjunct or monotherapy has been included [13] ( 1 recommended as an adjunct; 2 temporarily recommended as an adjunct; 3 mildly recommended as an adjunct; 4 mildly recommended as an adjunct or monotherapy; 5 mildly recommended as a monotherapy; 6 presently not advised as an adjunct; 7 presently not advised as an adjunct or monotherapy; 8 presently not advised as a monotherapy).…”

“…In managing manic episodes associated with BD, substances like lithium and atypical antipsychotics are often used [ 4 , 5 ]. Although many efficacious pharmacological agents are accessible, nearly 50% of patients remain unable to attain remission [ 4 ], and, with each successive episode, the likelihood of achieving remission diminishes [ 6 ].…”