National ketamine shortage puts therapy patients at risk

For decades, the hallucinogenic chemical ketamine has been widely used both as a medical anesthetic and as an illegal recreational drug. More recently, medical professionals have begun to embrace ketamine as a treatment for a range of mental health disorders. Over the last decade, ketamine therapy clinics have emerged throughout the U.S. with promising results, particularly for patients suffering from severe depression. Over the last several months though, ketamine has been difficult for therapy providers to come by due to a shortage of the drug. While it's unclear what exactly is causing the shortage, many patients undergoing ketamine therapy are unable to get the consistent treatment they need, worsening their mental health. To understand more about ketamine therapy, GBH's All Things Considered host Arun Rath spoke with Dr. Peter Grinspoon, a psychedelics educator and instructor in medicine at Harvard Medical School. What follows is a lightly edited transcript.

Rath: So first, tell us a bit more detail about these newer off-label uses of ketamine and the way it's being used to treat patients now.

Grinspoon: Well, off-label is the correct word. Ketamine isn't a first choice in treating anything unless you're talking about surgical anesthesia or veterinary anesthesia. But for people who have treatment resistant depression, if you've failed two or three different medications or treatments for depression, ketamine has been found to be incredibly helpful for a significant number of patients. Not only does it help breakthrough depression and help sustain them into remission, but it also does it really quickly, and it's safe to use for suicidal patients.

So it's no wonder, with tens of millions of people in this country suffering from depression, that the people are so interested in using ketamine.

Rath: We've seen reports with just extraordinary testimonials from people putting it in life-and-death terms. But it's not just anecdotal, there's research to back up how effective it is, right?

Grinspoon: Absolutely. There's substantial research showing that ketamine is effective for what it was approved for, for treatment-resistant depression. There's also some interesting research showing that ketamine is potentially very helpful for alcohol use disorder and obsessive compulsive disorder. So I think we're just at the tip of the iceberg of what ketamine could possibly do for us.

Rath: When we're talking about a treatment for depression, I saw one clinician quoted as saying that it's important to keep in mind that it's a treatment, not a cure. So what would it mean for a patient to not have access to the drug if treatment is actually ongoing?

Grinspoon: Exactly, it doesn't cure the treatment-resistant depression. It lifts the patient out of the treatment-resistant depression, oftentimes in about 40 minutes, as opposed to waiting to see if another psychiatric medication is going to work in weeks or months. So it's been like a wonder cure, and then to take it away from people just because of the supply chain shortage, which is a complex issue.

There a number of different things going into it. Part of it is increased demand. This can be very dangerous If you have a suicidal patient who's finally stabilized on ketamine. Again, you need to repeat the ketamine treatment. It doesn't cure the depression. You need maintenance therapy, and if you can't get access to ketamine, that's very, very dangerous because again, by definition, if it's treatment-resistant depression, they haven't responded to other treatments that aren't the ketamine.

Rath: One of the things we've seen cited in terms of being behind the shortage of the drug is some of the manufacturers apparently are saying they will not supply it for off-label uses. Why would they do that?

Grinspoon: Right, you wonder. I'm not sure, but you wonder if it's because of liability, if they're worried about about being sued. There's also just flat out supply chain problems, as I understand it, and then there's been an increased demand. You look at Wegovy, Ozempic — these weight-loss drugs, nobody can get these either, because all of a sudden everybody's taking them and the infrastructure to produce them has not gone up as drastically as the demand. When you have such a vast and rapid increase in demand and then you have the added problem of the manufacturers saying we're not going to supply this to off-label uses, you can see how there's a shortage, but it's very concerning.

Rath: Is there a pathway to getting approval for the use of this drug from the FDA or whoever that authority would need to be?

Grinspoon: I think there is going to be approval eventually, especially if more studies that are so glowingly convincing and glowingly positive come in. I think the FDA is going to have to approve it. However, there's still a lot of people that get it from these mail order online companies, and I just don't know if the FDA is going to go along with that. These ketamine clinics are also in a gray zone. They're also really expensive; it's thousands of dollars for ketamine treatment. It's hard to say how this is all going to settle out.

We are going to have ketamine clinics at Mass General at McLean Hospital, but how are all these other clinics are going to play out? If we have a lot of bad reactions, if that starts to get publicized, the FDA might be under pressure not to approve it. So it's a little bit of the wild, wild west out there right now, and it's a little hard to predict what's going to happen.

Rath: For the patients suffering from treatment resistant depression, do we have any sense of why ketamine can help when other drugs seem not to?

Grinspoon: We don't really know why. It's really interesting. Again, it helps really quickly. It can help in like 40 minutes, which is a huge deal if you've been depressed for months or years and nothing's working. You could lose hope that you're ever going to feel better, and then for it to work so quickly.

I'm not sure they understand the exact mechanism, it works on the glutamate neurotransmitter, and some people think it has to do with it being anti-inflammatory. Inflammation can contribute to depression, but I really don't think they've elucidated the exact mechanism by which ketamine treats treatment resistant depression yet.

Rath: Dr. Grinspoon This is fascinating. Thank you so much.

Grinspoon: Thank you so much for having me. What a great discussion.