About this Research Topic

Manuscript Submission Deadline 17 November 2022

Classic antidepressants typically require weeks to months to produce clinically significant effects. Considering that only one-third of patients achieve remission from depression with their first prescribed drug, a large proportion of patients will be submitted to several lengthy trials of antidepressants, and a big part of treatment time will be spent waiting and hoping for medications to work. Considering also that depressed individuals who commit suicide frequently seek help from mental health professionals weeks prior to completion of suicide, there is an emerging need for treatments that produce a faster onset of antidepressant action.

In recent years, some substances have achieved the status of 'rapid-acting antidepressants', and there has been great interest in the mechanism of action of drugs that are able to elicit such responses. NMDA antagonism, a property shared with ketamine and dextromethorphan, is thought to be one of these mechanisms, although it is unlikely to be the final pathway of rapid antidepressant action but a mediator of BDNF release. Scopolamine, a muscarinic receptor antagonist, also has BDNF-releasing properties, which are proposed to happen through activation of AMPA receptors and mTORC1 signaling. GABA-A allosteric modulators such as brexanolone and zuranolone, and 5HT2A agonists such as psilocybin, are also amongst this new class of drugs.

The aim of this Research Topic is to gather information and provide an update on these new compounds, as well as on more established drugs with newly discovered rapid antidepressant effects, focusing on their efficacy and their specific profile in different clinical, laboratory, or imaging outcomes. We will particularly value papers focusing on the identification of or detailing the individual and/or shared mechanisms of action of these drugs.

We welcome studies including, but not limited to, Original Research articles (clinical and pre-clinical), Review articles, Meta-Analyses, Case Series, Perspectives, and Case Reports, on substances with demonstrated rapid antidepressant properties, such as:
- ketamine
- ketamine enantiomers (esketamine, arketamine)
- scopolamine
- brexanolone
- zuranolone
- dextromethorphan-Bupropion combination
- psilocybin
- new rapid-acting antidepressants.

Keywords: ketamine, rapid acting antidepressants, scopolamine


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.

Classic antidepressants typically require weeks to months to produce clinically significant effects. Considering that only one-third of patients achieve remission from depression with their first prescribed drug, a large proportion of patients will be submitted to several lengthy trials of antidepressants, and a big part of treatment time will be spent waiting and hoping for medications to work. Considering also that depressed individuals who commit suicide frequently seek help from mental health professionals weeks prior to completion of suicide, there is an emerging need for treatments that produce a faster onset of antidepressant action.

In recent years, some substances have achieved the status of 'rapid-acting antidepressants', and there has been great interest in the mechanism of action of drugs that are able to elicit such responses. NMDA antagonism, a property shared with ketamine and dextromethorphan, is thought to be one of these mechanisms, although it is unlikely to be the final pathway of rapid antidepressant action but a mediator of BDNF release. Scopolamine, a muscarinic receptor antagonist, also has BDNF-releasing properties, which are proposed to happen through activation of AMPA receptors and mTORC1 signaling. GABA-A allosteric modulators such as brexanolone and zuranolone, and 5HT2A agonists such as psilocybin, are also amongst this new class of drugs.

The aim of this Research Topic is to gather information and provide an update on these new compounds, as well as on more established drugs with newly discovered rapid antidepressant effects, focusing on their efficacy and their specific profile in different clinical, laboratory, or imaging outcomes. We will particularly value papers focusing on the identification of or detailing the individual and/or shared mechanisms of action of these drugs.

We welcome studies including, but not limited to, Original Research articles (clinical and pre-clinical), Review articles, Meta-Analyses, Case Series, Perspectives, and Case Reports, on substances with demonstrated rapid antidepressant properties, such as:
- ketamine
- ketamine enantiomers (esketamine, arketamine)
- scopolamine
- brexanolone
- zuranolone
- dextromethorphan-Bupropion combination
- psilocybin
- new rapid-acting antidepressants.

Keywords: ketamine, rapid acting antidepressants, scopolamine


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.

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