[Clinical management of treatment-resistant depression].

Treatment-resistant depression lacks a standardized definition, but several promising pharmacological and neuromodulatory options exist. Current research emphasizes fast-acting, well-tolerated treatments beyond the monoamine hypothesis. Esketamine is an established fast-acting and well-tolerated therapy, while psychedelics and esmethadone remain in clinical trials. Off-label compounds like dextromethorphan and anti-inflammatory strategies are also discussed. Pharmacological approaches modulating the glutamatergic system or belonging to the psychedelic class are particularly important for current research, especially those with rapid clinical effects and favorable side-effect profiles.

Study at a glance

Abstract

Treatment-resistant depression (TRD) is a complex disorder. Although no standardized definition has been established to date, there are promising and well-established treatment options for the condition. Looking at the current pharmacological and neuromodulatory strategies, there is an urgent need for fast-acting and well-tolerated treatment options. The search for new mechanisms of action goes beyond the monoamine hypothesis. For example, esketamine is already an established treatment method that is fast-acting and well tolerated, while psychedelics or esmethadone are currently still undergoing clinical trials. Compounds that can be used off-label, such as dextromethorphan or anti-inflammatory strategies are also presented. Pharmacological approaches that focus on the modulation of the glutamatergic system or belong to the class of psychedelics, appear to be of particular importance for current research and development. These particularly include substances that rapidly exert clinical effects and have a favorable side-effect profile.