Depression, a global public health problem, affects the quality of life and health of millions of people.
According to the World Health Organization (WHO), depression is one of the leading causes of disability globally, affecting more than 264 million people worldwide. This figure highlights the prevalence and severity of depression as a serious mental health condition.
How should humans build a wall of defense in the face of depression?
Part.1 Depression is much more than a bad mood
Depression, which is characterized by a significant and persistent downturn in mood, is the main type of mood disorder. Its main symptoms include persistent sadness, loss of interest or pleasure, decreased energy, sleep disturbances, changes in appetite, decreased sense of self-worth, difficulty concentrating, and suicidal thinking or behavior.
Much more than just a bad mood, depression is a condition that needs to be treated.
Depression has far-reaching effects on an individual that are not limited to the realm of mental health. It has also been linked to a variety of physical health problems, such as heart disease and diabetes. In addition, depression has significant social and economic impacts, including reduced ability to work, increased demand for healthcare resources, and the financial burden associated with the illness.
To combat these negative effects, scientists continue to explore ways to treat depression.
Part.2 “Heart Diseases Require Heart Medicine
The causes of depression are multifaceted, including genetics, biochemical changes, environmental factors and the interaction of psychosocial factors. Because of the specificity of mental illness, the treatment methods for depression are also more diverse, usually including medication, psychotherapy or a combination of both.
Antidepressants are one of the most common methods of treatment and include several types of medications such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, and monoamine oxidase inhibitors (MAOIs). These medications relieve depressive symptoms by regulating the levels of specific chemicals in the brain. It usually takes a few weeks for the medications to start working, and it may be necessary to adjust the dosage or change medications to find the most effective treatment option.
In 2019, the U.S. Food and Drug Administration (FDA) allowed the first fast-acting antidepressant, S-ketamine (Spravato), to be marketed, which can produce antidepressant effects within 1-4 hours of a single dose in the clinic. Compared to traditional antidepressant medications, ketamine is fast-acting, providing significant improvement in patients’ depressive symptoms within hours, and can produce up to three times greater relief for depressive symptoms than conventional antidepressant medications, with only one dose of a subnarcotic dose. A single subanesthetic dose of ketamine can have an effect on depressive symptoms for up to two weeks.
The development of rapid-acting antidepressants is critical to improving the quality of life for people with depression. For those with severe depression, especially those at risk of suicide, fast-acting treatments can provide timely help and reduce patient suffering and suicide risk. In addition, the availability of rapid-acting antidepressants may also change the current treatment paradigm, providing patients with more options and hope.
But the drug is not without its harmful effects.The FDA had noted in 2019 that S-ketamine may impair attention, judgment, thinking, reaction time, and motor skills. The most common side effects for patients in clinical trials included schizophrenia, nausea, and elevated blood pressure.
An FDA warning document issued in February 2022 mentions that S-ketamine is strictly controlled in terms of dispensing and administration because of multiple potential risks of the medication. For example, patients must be administered the drug in an officially certified healthcare facility, and after the healthcare facility administers the drug, the patient must be monitored for at least two hours until it is safe for the patient to leave.
The use of ketamine in the treatment of depression is an important development in the field of psychiatric drug discovery and development, but at the same time it highlights the urgent clinical need for fast-acting antidepressants, as well as the grim state of affairs in the research and development of rapid-acting antidepressant drugs.
Is there a better drug than ketamine?
Part.3 New Drugs for Depression
Professor Hailan Hu’s team at Zhejiang University found that the target of ketamine’s antidepressant effect is the glutamate receptor in the lateral rein nucleus of the brain. The study indicates that the abnormal increase in excitability and cluster firing in the lateral rein nucleus of mice under depression is associated with an increase in calcium ion inward flow mediated by glutamate receptors. In addition, this increased excitability was associated with an imbalance in ionic homeostasis, especially the increased activity of the supracellular potassium channel 4.1 (Kir4.1) leading to a greater difference in the concentration of potassium ions between inside and outside the neuronal cell, triggering the opening of the glutamate receptors, which ultimately led to a lack of pleasure and the development of depressive symptoms.
Based on this, researchers at the Shanghai Institute of Pharmaceutical Sciences of the Chinese Academy of Sciences discovered in February 2024 that blocking the Kir4.1 potassium channel can produce a rapid antidepressant response, an important advance in the field of depression treatment. This study not only demonstrates a different therapeutic mechanism from traditional antidepressant drugs, but also provides a possible new treatment approach, which may be a ray of light representing hope for patients who do not respond well to existing treatments.
The discovery of the Kir4.1 potassium channel has provided a new direction in the treatment of depression. By blocking this channel, the depressive phenotype in animal models can be significantly reversed in a short period of time, an effect comparable to that of S-ketamine, but possibly with a better safety profile.
This means that future depression treatments may not only be able to provide more rapid relief of symptoms, but also reduce potential side effects and dependence problems.
Of course, while the discovery of the Kir4.1 potassium channel is an exciting advancement, more research and clinical trials are needed before this treatment can be applied to humans. This includes evaluating its safety and efficacy in humans, as well as determining the optimal mode of administration and dosage. Additionally, researchers need to explore whether this treatment is suitable for all types of people with depression and how it can be combined with existing treatments.
In conclusion, the discovery of the Kir4.1 potassium channel opens up new avenues in the treatment of depression and offers new hope for patients who continue to struggle with traditional treatments. With the depth of future research, we have reason to expect that more depressed patients will find the right treatment for themselves and regain their happiness.