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Discover NIMH: Drug Discovery and Development



>> JOSH GORDON: One of the most exciting recent breakthroughs from research funded by the National Institute of Mental Health, or NIMH, is the development of a fast-acting medication for treatment-resistant depression based on ketamine. This treatment is bringing new hope by making a life-changing impact on people and families affected by major depression. [music]

>> MJ CROM: My partner actually heard a story on NPR, um, that talked about ketamine treatment for treatment-resistant depression. I had been in treatment for depression for six or seven years at that point, and none of the treatments that I had tried had a lasting impact.

>> CARLOS ZARATE: Ketamine research has given us novel insights into treatment-resistant depression, the biology of it, and also the biology of suicidal ideation. We were interested in trying to find drugs that could do some very rapid onset of antidepressant effects, and ketamine targets a key protein in the brain and then the A receptor, which we believe would be responsible for rapid onset of antidepressant effects. [music]

>> JOSH GORDON: Ketamine is an anesthetic that increases activity in the dorsal anterior cingulate cortex, a part of the brain important for regulating emotion and evaluating threats and rewards. Research shows that ketamine can significantly decrease depression symptoms after just 24 hours.

>> MJ CROM: So I was an inpatient at NIH for about nine months. The very first infusion I got, uh, when I got to that point of feeling normal, I suddenly felt energy that I hadn't felt, literally, in years.

>> CARLOS ZARATE: What's different about our research with ketamine and other types of drugs is that they have this rapid improvement, very robust improvement, which is much different than any of the other treatments or types of research we've done before. We have technologies beyond imagination, from the latest brain image in sleep technologies to magnetic encephalography that permits us to study the brain in real time.

>> MJ CROM: As a patient who goes to the doctor who has depression, you don't hear about all of the really cutting-edge things that are-- that are being investigated and that might really help you. Hearing about all of that really made me feel like there was hope. Just because I had tried several antidepressants, and none of them had worked, that didn't mean that I was incurable, that I was never gonna feel better.

>> CARLOS ZARATE: Now that we can see that some of our patients have these remarkable changes in their life and their view of how they can perceive and function in life, it's just remarkable.

>> JOSH GORDON: In 2019, the FDA approved S-ketamine, a nasal spray derived from ketamine. It's the first truly novel antidepressant medication in decades and the first to target treatment-resistant depression.

>> CARLOS ZARATE: I believe our research has given hope to our patients and their families because treatment-resistant depression is really an unmet need, where there are very few treatments. We now have a treatment, can work in hours, which used to take weeks or longer for severe depression, suicidal ideation. Now that we can improve depression and suicidal thinking very rapidly, imagine the possibilities for the other mental disorders.

>> MJ CROM: The work that they're doing here is-- they're doing it because they really wanna help people. If I hadn't decided to join this trial, I wouldn't have discovered a treatment that really works well for me, and I wouldn't have gotten the, the hope and the sense of purpose that I got from participating. I think I'm on my way to sort of where I would prefer to be, as opposed to where depression had put me.

>> JOSH GORDON: NIMH-funded ketamine research didn't just pave the way to an exciting new treatment. It is also enabling a deeper understanding of the biological causes of depression and other brain disorders. This knowledge could lead to the development of other therapies and treatments in the future.