Before the new treatment-resistant depression therapy reaches the market, Iosifescu anticipates its benefits and limitations in real-world patients.
Last month, the US Food and Drug Administration (FDA) approved the New Drug Application (NDA) for esketamine nasal spray (Spravato) as the first novel therapy approved for treatment-resistant depression in 30 years.
Though the unique, fast-acting characteristics of the nasal spray are unheralded on the depression market, it’s not clinicians’ first experience with a drug of its kind. In an interview with MD Magazine®, Dan Iosifescu, MD, associate professor of Psychiatry at NYU School of Medicine, director of Clinical Research at Nathan S. Kline Institute for Psychiatric Research, and prominent ketamine investigator, explained prior to assessment and application of sibling drug ketamine has given clinicians an idea of what esketamine will look like on the market.
MD Mag: What will the first real-world results look like for treatment-resistant depression patients on esketamine?
Iosifescu: Well, the good news is that, although esketamine is new, its sister drug ketamine already has a track record. And we don't really expect dramatic differences in terms of the outcomes, both good and bad between the 2. So it's not catching us by complete surprise, in terms of what's going to happen down the line.
With every treatment, there are caveats and downsides. For ketamine and esketamine, here are the major ones: there are some side effects that happen at the time of treatment administration. Those side effects involve either the person feeling somewhat weird—psychotomimetic effects. Essentially, these are described as dissociation effects that happen for about an hour after getting the treatment. People described it as if they're looking at themselves from a distance, as outer-body experiences. Others feel like they're experiencing a high.
The good news is doesn't last longer than a few minutes to an hour after the treatment administration. But, it may not be pleasant.
The other thing that can be medically more serious is that people can have a significant increase in blood pressure and heart rate for a brief period of time after getting either ketamine or esketamine. And this is one of the reasons why it's not recommended to be administered at home, even if it's not intravenous but intranasal and patients are allowed to self-administer the spray. The device is made so that it's not too hard to give it to yourself, but you still need to be monitored for about 2 hours, in the doctor's office.
So, this is not going to be something that you can get a prescription for and can pick up from the pharmacy then give to yourself at home, because there might be a few people who it might have a very significant spike in blood pressure or heart rate, and that could lead to a stroke or a heart attack in some patients. The office that administers this should be prepared to intervene in some way, in the situation of a major shift in vital signs.
The other reason why it's not going to be recommended to be given at home is that ketamine is a substance of abuse. It's been used on the street as Special-K—usually in much higher doses than we recommend for depression. But ultimately, it is something that we don't want to encourage or foster a certain pattern of addiction, and that's the second reason why it will be an in-office procedure.
My expectation is that it will be available for patients, it will be expensive, and probably only for a very tiny minority will it be a long-term treatment. For the majority of individuals that benefit from it, it will be essentially buying them time for other treatments—be them pharmacotherapies or device-based treatment, or psychotherapies, because those are beginning to work much more slower than ketamine does.