The Pharmacotherapy of Depression - Searching for New Mechanisms and Drug Interactions. Basic and Clinical Research.

Depression is a common mental disorder and one of the leading causes of hospitalization. Simultaneously this disorder is the most notorious vulnerability factor to suicide attempts among men and women. The COVID-19 pandemic (COVID-19-related stressors) resulted in a statistically significant increase in depression incidences. Pharmacological treatment in the clinic is primarily based on substances synthesized in the 1960s and 1970s. High hopes were associated with compounds increasing the level of catecholamines in the brain and reducing excitotoxic levels of glutamate (Glu). However, side effects associated with cognition and psychosis are common. Therefore, it is crucial to synthesize new pharmacologically active substances or combine those used in clinical practice to define further directions in the development of novel more effective therapeutics for depression.

The main goal of this special issue is to define novel pharmacological molecular targets and new interactions between administered drugs (used in the clinic and also new compounds) to increase the effectiveness of therapy as well as to limit the side effects (such as psychosis or cognitive abnormalities) characteristic of currently available antidepressants. For example, ketamine (uncompetitive NMDAR antagonist) as a fast-acting compound turned out to have unwanted side effects such as somnolence or psychosis, which prevented clinical use. The molecular mechanism of ketamine action should be better investigated. On the other hand, classical antidepressants have long-term effects and are also burdened with numerous side effects. That is why it is critical to search for new mechanisms, interactions, and signalling pathways as targets of pharmacotherapy of depression. This issue is addressed to collect and present new methods/attempts of treating depression based on clinical and basic research.

• We welcome submissions covering but limited to: pharmacotherapy, basic research, clinical use, new compounds, new interactions, new mechanism, new pharmacological targets to treat depression, Glu, excitatory synapse, GABA, adhesions, scaffolding proteins, PSD-95, membrane acting compounds/mechanisms, receptor acting compounds, new receptors

• Various type of papers are welcome, including original research articles (basic and clinical), review papers, commentaries

Keywords: Depression, pharmacotherapy, new mechanisms, new drugs interactions, side effects

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.