Neurosteroids identified as potential therapy for depression resistant to treatment

Depression, characterized by persistent sadness, despair and lack of interest in activities previously appreciated, is one of the most common mental health problems. Recent estimates by the World Health Organization (WHO) suggest that around 5% of the world’s population suffers from depression.

For decades, researchers have been trying to design safe and effective treatments depression which cause minimum or without side effects. This led to the introduction of a wide range of treatment strategies, ranging from psychotherapy and Alternative medicine a wide range of pharmacological drugs, including Selective serotonin reuptake inhibitors (ISRS), inhibitors of the recovering of serotonin-nortothephrine (SNRI), tricyclic antidepressants (TCA), monoamine oxidase inhibitors (MAOI) and atypical antidepressants.

Most people diagnosed with depression end up finding appropriate treatment for them via a test and error process, which ultimately led to their recovery. Some people, however, can live severe depression For prolonged periods, note that no treatment ultimately facilitates their symptoms.

In recent years, various pharmacological and neuroscientific studies have explored the potential of neurosteroids, natural steroids synthesized in the brain, for the treatment of depression in people who did not benefit from other widely used treatment strategies.

Neurosteroids are compounds that modulate various neuronal routes, including the central system of response to the stress of the brain (that is to say the hypothalamo-pituitary-surrenalian axis), as well as the GABA_A receptors, the inhibitory receptors that contribute to the activity of the brain and to the NMDA receptors, and memory.

SMT researchers. The Kishurita Bhoyar College of Pharmacy in India recently examined the previous literature evaluating the potential of neurosteroids to combat depression cases which are difficult to deal with using existing pharmacological treatments. Their paper, published In Neurosciencehighlights the potential of neurosteroid treatments, suggesting that they can increase neuroplasticity and positively affect the neuronal routes compromised by depression.

“Treatment resistant depression (TRD) is a severe and persistent subset of major depressive disorders (MDD) which does not respond to at least two different classes of antidepressants,” wrote Krutika Nagpurkar, Pratik Ghive and their colleagues in their article. “Given the limits of conventional treatments, neurosteroids have become promising alternatives due to their rapid and multiple mechanisms of action.”

As part of their study, Nagpurkar, Ghive and their colleagues examined the results of recent preclinical and clinical trials evaluating the effects of neurosteroids on individuals who have been diagnosed with MDD, the most serious and persistent form of depression, but which did not benefit from at least 2 different types of antidepressive drugs. These studies have used a variety of neurosteroids, including allopregnanolone, pregnolone and dehydroepiandrosterone (DHEA).

“Neurosteroids modulate the key systems of neurotransmitters, including Gamma-Aminobutyric acid (GABA_A) and the N-Methyl-D-Aspartate (NMDA) receptors, improving inhibitory transmission and promoting synaptic plasticity“explained Nagpurkar, Ghive and their colleagues.

“They regulate the hypothalamic axis – pituitary -surrenal (HPA), attenuating the neurotoxicity linked to stress and restaurant neurochemical balance. Plurgal studies have demonstrated the efficiency of neurosteroids in the inversion of depressive type behaviors in chronic stress models, while clinical trials highlight their potential for anti -depress effects antidepress supported and supported. “. “”

In 2019, Food and Drug Administration (FDA) approved the use of Brexanolone neurosteroid for the treatment of postpartum depression in the United States. Currently, however, Brexanolone remains difficult to access and its long -term effects remain poorly understood.

“This review explores the therapeutic potential of neurosteroids in TRD, discussing their mechanisms, clinical evidenceAnd future orientations, “wrote Nagpurkar, Ghive and their colleagues.” The results support the integration of treatments based on neurosteroids in the management of TRD, offering new hope to patients who do not respond to conventional antidepressants.

“This review particularly highlights paradigm shift Offered by neurosteroids, going beyond the traditional monoamine hypothesis and positions them as new multi-target therapies capable of treating complex neurobiology of the TRD. “”

Overall, the results of the analyzes carried out by this team of researchers suggest that neurosteroids are in fact a viable and promising alternative treatment for serious and persistent depression which cannot be treated using existing antidepressants. Based on the observed results of neurosteroids on the brain, Nagpurkar, Ghive and their colleagues have hypothesized that they could also be useful for dealing with other mental health disorders related to stress.

This journal document could soon inspire other studies aimed at studying the long -term effects of taking neurosteroids, which have not yet been elucidated. In addition, they could inform pre-clinical and Clinical trials aimed at testing the potential of these compounds for the treatment of other psychiatric conditions.

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