Neuropharmacological Targets for Depressive Disorders and Seizures

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About this Research Topic

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Background

According to global statistics, there are over 320 million people suffering from depressive disorders and this number is growing alarmingly. These heterogeneous diseases are induced by biological, psychological, genetic, and environmental factors. At present, the COVID-19 pandemic has also contributed to concerns about the mental health of the human population around the world. Consequences of such a high incidence of depressive disorders affect patients, their families, and thus society due to the fact that depressive disorders severely reduce the quality of a patient’s life as well as affect their professional and social activities which can lead to suicide attempts and deaths. The medical world is aware that the available antidepressant pharmacotherapy, which is mainly based on the monoamine hypothesis of depression, is not sufficient. Up to 40% of depressive patients do not respond to antidepressant drugs, up to 60% of patients do not achieve complete remission, and up to 50-85% of individuals with depression experience relapse of the disease. A delayed onset of the biological action of antidepressants as well as their adverse effects further reduce treatment effectiveness.



Depressive disorders are frequently accompanied by other diseases, including epilepsy. It has been shown that more than 13% and 23% of pediatric and adult patients with epilepsy, respectively, are also diagnosed with depression. Conversely, those diagnosed with depressive disorders have twice the risk of development of epilepsy. Like depressive disorders, the management of epilepsy is highly difficult particularly due to pharmacoresistancy (ca. 30% of patients), serious side effects of antiepileptic drugs, their dangerous interactions with other substances, and withdrawal symptoms. Additionally, comorbidity of depressive disorders and epilepsy may negatively affect the effectiveness of antidepressant/antiepileptic treatments resulting in increased seizure severity, elevated risk of depressive episodes/epilepsy-related accidents and injuries, increased side effects of antiepileptic drugs and potentially elevated mortality rate due to suicides.



Due to these problems with antidepressant drugs affecting the serotoninergic, noradrenergic and dopaminergic pathways, a ceaseless search for novel treatment strategies for depressive disorders, that will allow to improve both effectiveness and tolerance of pharmacotherapy, has been made. Thus, active substances with molecular targets localized outside the monoaminergic system are particularly enthusiastically investigated. Innovative combinations of well-known compounds are also taken into consideration.

Since depressive patients share similar changes in the hypothalamic-pituitary-adrenal axis and neurotransmissions with epileptic patients and since these two conditions quite often co-occur, it would be ideal to extend the available arsenal of antidepressant drugs with new preparations effective in both diseases.



In our Research Topic on Neuropharmacological targets for depressive disorders and seizures, we would like to bring together experts working in the field of these two medical conditions and invite them to present their opinions and suggestions related to pharmacotherapy of depression and/or epilepsy, based on latest results from pre-clinical research and clinical trials.



We encourage to submit Original Research articles, Reviews, reports from Clinical Trials, and Case Reports that cover recent strategies in the management of depressive disorders/epilepsy, particularly targeting:



• glutamatergic system

• endocannabinoid system

• opioid signaling

• mTOR pathway

• purinergic receptors

• neuroinflammation

• neuroplasticity

• hypothalamic-pituitary-adrenal axis

• neurokinins

• P-glycoprotein

Keywords: depression, seizures, glutamatergic system, endocannabinoid system, mTOR pathway, neuroinflammation, neuroplasticity

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