Depression affects more than 264 million people People of all ages worldwide. The World Health Organization lists depression as one of the most harmful diseases to society.It is the main cause of disability worldwide, and the most common psychiatric diagnosis related to suicide, accounting for nearly 800,000 deaths worldwide Per year. People with depression may not be able to manage life needs and maintain social connections, which affects all aspects of their experience, from school and employment to interpersonal relationships and overall quality of life.
Speaking of treatment, About one-third Of those who suffer from depression do not respond to two or more antidepressants and are considered treatment resistant. Refractory depression is a chronic disease that brings more emotional, functional and economic burdens to individuals, their relatives and society. It is also related to higher morbidity, higher medical care costs and various comorbidities.
Although there are many antidepressants, they all work by changing the levels of brain signaling molecules called monoaminergic neurotransmitters. The development of new drugs to treat depression has been stagnant for many years, and many pharmaceutical companies have completely withdrawn from the field of neuroscience. But recent scientific advances have led to the development of new antidepressants that work through a completely different mechanism.
The brain is the most advanced adaptive information processing system in existence-largely because of its huge plasticity. Scientists have been developing new, fast-acting antidepressants based on these advances in neuroscience. In this regard, a large amount of evidence shows that the regulation of the two receptors on many neurons-AMPA and NMDA-controls the neurotransmitter glutamate to control the changes in the tiny connections or synapses between neurons. Think of this synaptic plasticity as a mechanism that manipulates the intensity of information flow in these tiny gaps between brain cells. Based on this research, scientists have demonstrated that blocking the NMDA receptors on inhibitory neurons, thereby promoting the release of glutamate, can exert a rapid antidepressant effect in treatment-resistant depression. In fact, this discovery led the U.S. Food and Drug Administration and the European Medicines Agency to approve esketamine, an NMDA antagonist for the treatment of refractory depression in 2019. (Esketamine is chemically related to ketamine, anesthetics, and the hallucinogen ketamine.) Institutional approval opens up the possibility of developing next-generation treatments in this course. Although the dose used for treatment is very low, esketamine is highly selective, but it does target all NMDA receptors. It may be that some NMDA receptors are more responsible for their therapeutic antidepressant effects, while others may be more responsible for certain side effects.Therefore, the next generation of certain NMDA antagonist drugs possible Reduce some side effects while maintaining efficacy.
Also in 2019, the FDA approved intravenous alloprogesterone as a first-class drug for the treatment of postpartum depression. Alloprogesterone is a neuroactive steroid that is structurally similar to progesterone and acts on GABA receptors. It is believed to amplify GABAergic signals throughout the brain to improve symptoms of depression and anxiety. Zuranolone is an oral formulation of alloprogesterone, which is currently being tested more widely for the treatment of resistant depression.
Psychedelics, such as psilocybin, can also work.In a landmark exploratory experiment New England Journal of Medicine Earlier this year, Compare psilocybin with the widely used antidepressant escitalopramAlthough it is impossible to detect differences between drugs, many positive results—response levels and symptom relief—are more common in individuals treated with psilocybin. This has rekindled interest in psychedelic therapy as another way of drug discovery. Other new methods are also in the drug development pipeline, and each of them can add important new drugs to treat this debilitating disease. The Orexin system regulates neuronal limbic circuits associated with depression, and trials of Orexin 2 receptor antagonists are ongoing. Emerging evidence suggests that neuroimmune factors may play a role not only in neurodegenerative diseases, but also in depression. Microglia are resident immune cells in the brain, and P2x7 antagonists (regulate the function of microglia) are being studied. Finally, scientists are exploring innovative ways to increase the body’s own cannabinoid levels (rather than using cannabis or other external sources of cannabinoids) as a new type of antidepressant.
Despite the progress, there are still unmet needs in the field of mental health, including tailoring specific treatments for specific patients, adequately treating cognitive symptoms of schizophrenia, ensuring durable prevention of recurrence and continuing efficacy in most cases and achieving Better function (not just symptoms) results.
It is these treatment gaps that have prompted industry, academia, and the government to continue studying depression, discovering and developing new and more effective treatments for those who still continue to experience symptoms and cannot fully recover from existing treatments.
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