This month, the FDA approved the use of esketamine, a nasal spray based on the old anesthetic and once-popular club drug ketamine, to treat people with severe depression that has not responded to other treatments. It’s costly and entails visiting the doctor for four hours a week for four weeks, but it’s the first treatment in decades that works in a new way in the brain. That means it might reach the large number of people with depression who are not helped by drugs that target other brain functions.
Last March, Ronald S. Duman, Ph.D., wrote for Cerebrum on “The Dazzling Promise of Ketamine,” exploring how the drug was validated as an antidepressant, how it works, and what it could mean for development of other drugs:
Ketamine is an antagonist of the NMDA (N-methyl-D-aspartate) receptor, one type of receptor for glutamate, the major excitatory amino acid in the brain. At high doses, the drug is used as a dissociative anesthetic, producing catalepsy, catatonia, analgesia, and amnesia, that is often used for pediatric and veterinary medicine. A single low dose of ketamine, however, produces rapid antidepressant actions that last for approximately one week in most individuals. The discovery of a new, rapidly acting class of drug with a completely novel mechanism is arguably the biggest breakthrough in the field of depression in over 60 years. However, ketamine also has side effects, notably dissociative and psychotomimetic actions that, while transient, have limited its widespread use.
In a podcast with Cerebrum editor Bill Glovin, Duman got into more detail on what this means for patients:
Ketamine … acts within a matter of hours in some people, maybe a little bit longer. On average I think it’s two to four hours after a single dose, which is really an incredible finding …I think for most of my career, the field of depression and antidepressant treatment considered a rapid-acting agent like this was not possible. That in and of itself is really an incredible advance for the field.
If you have the means, people who don’t respond to the approved antidepressants can go out and seek treatment, as I mentioned, at maybe a pain clinic. Things are beginning to change in the landscape here in Yale New Haven Hospital. There’s a clinic that’s been open now for about a year where you can come in and, under a psychiatrist’s supervision, receive ketamine administration. It is now approved for coverage by the insurance companies, so that’s a big step forward. It’s still very expensive, I think here at Yale New Haven Hospital, it’s probably a little over $1,000 per treatment. For the insurance companies, the trade-off is that these are people who are really sick, very depressed, and could end up in the ER or in the hospital. For [the insurers], it’s still worthwhile, and it makes economic sense, to cover the cost of the ketamine administration. (podcast, transcript)
In 2017, we posted a news story on another use of ketamine: as a possible preventive for post-traumatic stress disorder (PTSD). Writer Kayt Sukel asked researcher Christine Denny about its potential after Denny showed proof of concept (in mice):
“I would not propose to give ketamine every week to military personnel or other people who know they are going to experience a big stressor,” she says. “But I think this work is a great starting point that can lead us to develop new methods to protect against PTSD and stress-induced depressive behavior. We don’t wait for polio to happen and then give someone a polio vaccine. So, if we can start thinking about preventive measures that we can put in place to help people avoid developing these kinds of mental disorders, to use prevention in psychiatry the same way we do in other parts of medicine, we may have the opportunity to really make a difference.”