On Tuesday (March 5), the U.S. Food and Drug Administration (FDA) approved a nasal spray for patients with depression who haven't responded to other treatments.
But what makes this newly approved treatment so different?
The drug, called Spravato and made by Janssen Pharmaceuticals, contains the active ingredient esketamine. This substance has the same molecular formula as ketamine but a different chemical structure. (In other words, it contains the same type and number of elements but in a different configuration.) Ketamine is typically used as an anesthetic, but it’s also been used as an illicit party drug.
One reason experts are excited about the nasal spray is that its effects can be seen within several hours to days. Other antidepressants, meanwhile, can take weeks to start working. [7 Ways Depression Differs in Men and Women]
医学专家们对XXX鼻腔喷剂感兴趣原因，就是疗效快，几小时或几天就能见奇效。与此相比，一般抗抑郁药则要数周。[ 男性和女性抑郁症的7种差别 ]
Antidepressants work by regrowing brain cells and the connections between them, and appears to have the same effects, said David Olson, an assistant professor of chemistry, biochemistry and molecular medicine at the University of California, Davis. But, these effects likely start much sooner than with other antidepressants, he said.
加州大学戴维斯分校（the University of California, Davis）的化学、生物化学和分子医学助理教授大卫·奥尔森（David Olson）说，抗抑郁药是促使大脑长出新细胞和改善神经细胞相互连接，与功能似乎相同。但是，这种药比一般抗抑郁药见效快。
Still, it's not entirely clear how the drug works.
e-like drugs are "dirty”, meaning they likely hit a variety of targets in the brain, Olson told Live Science. "There are a lot of very interesting hypotheses out there, [and] many of them are probably partially valid."
One idea is that e treats depression by blocking a neurotransmitter called glutamate from binding to the NMDA receptor, and stopping signals from cascading across the brain, Dr. Alan Schatzberg, a professor of psychiatry and behavioral sciences at the Stanford University School of Medicine, told Live Science.
斯坦福大学医学院（Stanford University School of Medicine）精神病学和行为科学教授艾伦·沙茨伯格（Alan Schatzberg）博士告诉“生命科学”记者，治疗抑郁症是通过阻止一种被称为谷氨酸的神经递质与NMDA受体的结合，切断信号通过大脑。
Glutamate is a chemical that brain cells use to send signals to other brain cells. But high levels of it can cause over-excitement in the brain, which can, in turn, damage brain cells.
A more controversial idea is that e binds to opioid receptors, causing a release of naturally occurring opioids in the body. Schatzberg and his team published a small study on this last summer in which they gave patients with depression ketamine twice — once after receiving an opioid-blocking drug, and once after receiving a placebo in place of the opioid blocker. The two treatments took place about a month apart, and neither the participants nor the researchers knew whether patients received the opioid blocker or the placebo. The study found that the patients responded well to the ketamine treatment if they didn't receive the opioid-blocking drug, bute had no effect on those that did, suggesting an opioid-like role.
This hypothesis has some experts concerned about -based drugs as a depression treatment.
"My concern about this compound is that it is a disguised form of opiates," said Dr. Mark George, a distinguished professor of psychiatry, radiology and neurosciences at the Medical University of South Carolina. While George said he is "overjoyed" for the prospect of a new treatment option, "I'm alarmed that there is pretty clear evidence [that] the way works is through the opioid system."
美国南卡罗来纳医科大学（Medical University of South Carolina）精神病学、放射学和神经科学着名教授马克·乔治（Mark George）博士说：“我们注意到XXX类药化学分子是阿片类药变体形式。现在有足够资料证明，它通过阿片类药理系统医治疾病。”乔治对这种治疗新选项前景表示“乐观”。
If this is the mechanism thae acts through to treat depression, its effects won't last and people might develop a tolerance to the drug, possibly even becoming addicted, George told Live Science. But if its antidepressant effects come from other mechanisms, such as blocking the NMDA receptor, then "that's good," he said.
Olson, however, said that he is less convinced by the opioid hypothesis and thinks more work needs to be done before ringing the alarm bells.
What's more, the new drug will see limited use. The medication comes with a risk of sedation and dissociation, such as difficulty with judgment, attention and thinking. Because of that, the nasal spray was approved to be used only under a "restricted distribution system," according to a statement from the FDA.
更重要的是，新药临床应用受到限制。它具有镇静和分解风险，会出现判断力、注意力和思维能力下降。因此，FDA文件规定，XXX药鼻喷剂只允许在“有限范围条件（restricted distribution system）”下采用。
This means that only patients with severe depression who haven't responded to at least two antidepressant treatments can receive the drug. In addition, the treatment is administered only in doctor's offices, and patients must stay in the office and be monitored for several hours after receiving the treatment.
Ultimately, despite some potential problems with the newly approved drug, experts are hopeful it will come through strong.
"I think that the FDA approval of is a huge landmark in the history of treating neuropsychiatric diseases," Olson said. "e really represents a leap forward in terms of new ideas for attacking depression and related neuropsychiatric diseases."
Editor's Note: This story was updated on March 7 to include additional information about Dr. Alan Schatzberg's study.
Originally published on Live Science.