The Journal. - The New Hit Depression Treatment? A Ketamine-Derived Nasal Spray

Episode Date: March 21, 2025

After it was approved in 2019, Spravato, a depression treatment derived from the club drug ketamine, was looking like a dud. But recently it has taken off, and it surpassed $1 billion in annual sales last year for its maker, Johnson and Johnson. Further Listening: -A Lawyer Says He Doesn't Need Help for Psychosis. His Family Disagrees.  -America's Maternal Mental Health Crisis  Further Reading: -J&J’s Ketamine-Derived Drug Is Taking Off  -Big Pharma Walked Away From Mental Health. Why Some Are Coming Back.  Learn more about your ad choices. Visit megaphone.fm/adchoices

A quick heads up before we get started. This episode mentions suicide and discusses depression. Please listen with care. So just to start us off, could you introduce yourself, your name, your age, what you do? My name is Sean Fury. I am a writer in Fort Worth, Texas. I'm 36 years old. And I'm seeing some, like a very interesting background there for you.

You've got a poster. You've got, is that Creature from the Black Lagoon? It is. That's my favorite. Sean loves movies, but he doesn't just love to watch them. He makes them too. Horror is my go-to. We just finished the first leg of a shoot of a horror thriller.

It's a vampire film. Why did you want to make this film? You know, to kind of work through my own issues with that depression and anxiety PTSD. And I chose a vampire type story because I feel like there are times where I felt really low where I just feel like I'm sucking the life out of my family, my wife. Yeah, so I decided to make that literal and explore it through a vampire film. Sean says depression has been part of his life for as long as he can remember. At times, he says, it's been debilitating.

There are days where my wife has to physically help me out of bed. I just can't get up. I can't really bear to face the day. What kind of treatments have you tried over time? Pretty much anything that came onto the market, I tried. And it is hard because you start taking it and you don't notice if it works or not for a couple of weeks. And then by that point, you have to kind of wane yourself off of it to try something new. And in the meantime, those antidepressants

can have several side effects on your body, which are frustrating as well. Sean has what's called treatment-resistant depression. And a few years ago, he found out about a new kind of treatment that might help him. It's called Spravato, and it's made by Johnson & Johnson. And spravato is unique because it's a derivative of ketamine, best known as an illicit club drug.

What impact has spravato had on your life? How would you describe that? Oh, man. I still have outlier days, but I am so much more positive and so much able to better roll with the punches just of life. People notice that you walk in a little more confident, you're a little bit taller, I think just more ready to go versus being depressed and just kind of floating from room to room, you know? Patients with results like Sean's have propelled sales of Spravato.

Last year, it exceeded a billion dollars in sales worldwide, becoming a blockbuster drug for J&J. For the pharmaceutical industry, it's amplifying the potential of psychedelics as a treatment for mental health. Welcome to The Journal, our show about money, business, and power. I'm Jessica Mendoza. It's Friday, March 21st.

Coming up on the show, how ketamine-derived treatment for depression became a hit for Johnson & Johnson. ["Sweet Home Alone"] My parents have had a lot of time on their hands lately. At first, it was nice. Hey, Mom, can you drive me to soccer practice? Sure can. We're having slow-cooked ribs for dinner.

It was awesome. And then it became a lot. Some friends are coming over to watch a movie Oh, what are we watching? I'll make some popcorn Thanks to Voila, they can order all our fresh favorites from Sobeys, Farmboy, and Longos online Which is super reliable and now my parents are reliable a little too reliable Voila your groceries delivered just like that Voila, your groceries delivered just like that. Nearly 30% of adults in the US say they've been diagnosed with depression at some point in their lives, according to a Gallup survey.

But even though depression is so prevalent, and in recent years more widely discussed, the way we treat it hasn't evolved for years. Why is depression so hard to treat? Yeah, I think that's a very good question. So in contrast to some what we might call physical illnesses, illnesses of the brain and the mind are less well understood. Dr. Hussain Emanji is a neuroscientist and professor of psychiatry at Oxford University. And for years, he worked at J&J, coming up with treatments for depression.

Depression is unfortunately one of the most disabling conditions there is. And although we've had a number of treatments, many people don't respond to them, so there's a real need to come up with improved treatments. In the late 80s and early 90s, the pharmaceutical industry made some breakthroughs in the field of mental health treatment with the success of Prozac. Prozac Weekly is here. Ask your doctor if it's right for you.

And Zoloft. Zoloft, when you know more about what's wrong, you can help make it right. These drugs are called SSRIs, and they boost serotonin levels in the brain. They're some of the most common treatments for depression, and they're effective, but results vary. One of the things that sometimes surprises people is that almost all our existing antidepressants, even when they work, take about four to six weeks to work. And that led many people, including myself, to think maybe we're hitting the wrong target,

that just increasing levels of serotonin is a starting point. Ultimately, you need to bring about other changes, which results in people getting better. Hussain wanted a medicine that worked quickly and could help people with treatment-resistant depression. Instead of boosting serotonin levels, he thought a better strategy for dealing with depression

was to help the brain cells create new connections. So Hussaini went looking for a substance that could do that. And he found a good option, ketamine. Ketamine is best known as a psychedelic. It's often used illegally at clubs and is popular for its hallucinogenic effects. It can make people feel detached from reality and kind of spacey. Ketamine, known on the streets as special K, vitamin K, or cat valium, a street drug police say is starting to resurface.

It is usually snorted or swallowed. The desired effect is euphoria, a dreamlike state. Ketamine is a controlled substance which comes with a risk of addiction and abuse. But it has also been used legally for decades as an anesthetic. So I was involved in some of the earlier studies using intravenous ketamine and those studies really showed remarkable effect. ketamine and those studies really showed remarkable effects. So we were looking at patients who are sometimes called treatment resistant depressed patients and in those patients we saw that within 24 hours 70% of those patients were classified as responders and what was interesting was that although the drug, the ketamine, is gone from your system within two to four hours,

people remained well for at least four days. In 2008, Hussaini was hired to become the new global head of neuroscience at J&J. He started working to create an effective medication for treatment-resistant depression. Hussaini believed ketamine could provide a breakthrough. But first, he needed to convince J&J. When I first brought up the idea, I think understandably people had some reservations because ketamine has sometimes been used as a club drug. So I had to really sort of walk through a lot of the reasons why I thought this would be

successful. How long before you were able to change their minds? Did it take a lot of arguing on your part? Yeah, I think it's fair to say that it was done in stages. So, you know, the initial discussions centered around, look, we think this is a good idea. Let's go ahead and generate some of the data. Knowing these risks,

Hisani and his team worked on minimizing them as much as possible. He came up with the idea of putting a very small amount of a derivative of ketamine into a nasal spray device. It's like an inhaler, except it's delivered through the nose. Basically, the person comes into the clinic, their dose is calculated, and they self-administer it. So they administer it in the nose themselves. And then there's no drug left in the device.

So you throw away the device. This device also had the added benefits of getting the dose to the brain faster than taking a pill would and was more convenient than using an IV. What were the challenges of testing this drug on patients? What were the risks involved? Sure. So it's basically two side effects.

One is that you get a slight increase in blood pressure after you take it, and it's about the blood pressure increase that you or I might have if we ran up a flight of stairs. The second thing is something called dissociation. So what dissociation is that you might feel that the colors around you are brighter or the sounds are louder, et cetera. For almost everyone, you know, it sort of starts within about half an hour,

at about one hour it's gone. Dissociation, is that like tripping? I think so. I think it's a low, low-level tripping. Very low-level tripping. Because of these side effects, the drug would have to be administered under medical supervision in a clinic. In testing, Hussaini and his team saw real results. He noted how the dissociative feelings wore off after about an hour, but the sensation induced a longer-lasting chemical change in the brain that reduced depressive symptoms.

The nasal spray had to go through many rounds of clinical testing, with some shown to improve depression while others showed no improvement over a placebo. In 2019, the FDA approved Spravato for patients with treatment-resistant depression, to take along with another antidepressant. All new tonight, a controversial new treatment for depression. The FDA approved the antidepressant this week, and it's a nasal spray. Spravato is the first new type of depression treatment since Prozac was OK'd back in 1987. At the time, J&J put the list price for Spravato between $590 and $885 per treatment session.

For Hussain and his team, the FDA approval was a huge breakthrough. You know, we got the call while the whole team was together, and obviously we celebrated right after. Were you popping champagne? It wasn't quite champagne, but we were really happy. OK. But Spravato got off to a shaky start. Because it had to be taken in a clinic under supervision, doctors and patients had more of a learning curve

than typical medication. And then the pandemic made that sort of in-person treatment even harder. How Spravato turned into a blockbuster is next. Hey, are you in the mood for something new? Why not fly with Air Transat to an eclectic music scene? A vibrant nightlife and your next big discovery. Starting this summer, you can fly direct from Toronto to Berlin, exclusively with Air Transat. Now all things Berlin feel closer than ever.

Air Transat, travel moves us. When you first heard about a ketamine treatment for depression, what did you think? I associated it, ketamine, with like microdosing LSD, which I was very nervous, hesitant to try. And I could not find any research about it online or reviews or testimonials of people who have actually undergone that treatment, which was very worrisome. Sean Fury, who we heard from earlier, was encouraged to try Spravato by his psychiatrist because he was continuing to struggle with his depression.

What changed your mind? I think I just, I got, it got so bad, having, you know, suicidal thoughts and all of that. And I think finally I just hit a breaking point where I was like, okay, we'll try Spravato and see how that goes. At that point I felt like maybe I didn't have anything to lose. Sean attended his first appointment in 2023. The treatment was covered by his insurance. How did that first session leave you feeling afterwards?

It was very jarring. I remember being surprised and nervous and wondering if this was something I wanted to keep doing, if it was going to be like this every time. But Sean went back the next week, and the next, and the next. And how did your body feel after taking it? The first probably 40 minutes, I feel it the most. You feel lighter, you know, you get like tingling sensations a bit. I let my mind just kind of wander.

And it wears off after about 40 or 50 minutes or so. And that second hour is just trying to be calm. It hits different every time. There are some days where I come home and immediately take a nap, just because I'm just tapped out. And there are other days where I'm home and immediately take a nap, just because I'm just tapped out. And there are other days where I'm ready to go. In the two years he's been taking it, Sean says he's only experienced hallucinations twice.

He told me about the first time it happened. Even though they had told me about it, I was not prepared at all for that. I remember that being very scary. And thankfully, my wife is there at the treatments with me, and so she was holding my hand and talking to me through it. Because when I'm taking this bravado, that feeling that I get is kind of being somewhere between reality and dreaming. So your mind's going a million miles an hour, but you can still hear what's going on around you. And that was very jarring at first.

But overall, Sean says Spravato has worked for him. I could handle things better than I could before I'd started taking Spravato. Just like the daily stresses of life, I noticed they were able to just kind of roll off my shoulders a bit easier than they would before. My confidence came back to some extent. I felt like the shell had broken and I was able to finally kind of breathe again.

The biggest thing is that I recognize when I'm having those negative thoughts, which before I used to, it never even occurred to me that I was kind of spiraling into this cycle of negativity and kind of self-abuse. When that starts happening now, I recognize it pretty much right away and I'm able to kind of ground myself or redirect my thoughts. And that's been the biggest change, the most powerful change to me. Since its slow start, Spravato has steadily grown its sales. J&J offered assistance to doctors who were interested in setting up clinics like the one Sean goes to.

And like so many pharma companies, J&J also invested in an ad campaign. With fewer depression symptoms, you may begin to feel like yourself again. Ask your doctor about Spravato. Since the beginning of 2023, prescriptions for Spravato have nearly doubled in the U.S. to more than 46,000. But with an estimated 3 to 5 million people suffering from treatment-resistant depression, according to J&J, the company has high hopes for the drug's potential. J&J predicts that it could make them $5 billion annually. Here's a company executive from an earnings call in January.

And Zvato is also the only antidepressant to ever receive breakthrough designation from the FDA. So great momentum and a long-term commitment to patients suffering with depression. Spravato's success shows the challenges and opportunities for big pharma when it comes to mental health treatments. And it's also giving hope to companies

working in the field of psychedelic research. There are now dozens of startups studying the effects of drugs like LSD and psilocybin on mental health. And last year, the industry seemed poised for another breakthrough. The FDA considered approving MDMA for treating PTSD, a condition that affects 13 million Americans. But the agency decided that drug needed more testing.

Hussaini, who has now left J&J, told me he thinks that the success of spravato could mean we see other non-traditional drugs being used as treatments. I think there's no doubt it's opened the door. I would say both, you know, sort of this different type of treatment and then what spravato has also been able to do is, you know, sort of normalize to some extent the in-clinic administration. So I think that's one of the things that until Spravato came along, that simply wasn't the case. So I think it certainly has opened the door.

But there are still unanswered questions about the future for patients taking Spravato. A J&J spokesperson told us that over six years of testing, the treatment remained effective and, quote, no new or unexpected safety issues were seen during long-term use. I spoke to one psychiatrist who runs a Spravato clinic, and he raised some concerns about patients taking the drug beyond six years. I asked Haseini about this.

Would you say Spravato is a long-term or a short-term treatment? I would say probably it'll depend on the indication. So I would say for treatment-resistant depression, it may be slightly more of a longer-term treatment because it just suggests that they've got bad illness. If they're not on treatment, the illness might come back. In January, the FDA went one step further in its approval of spravato by removing a condition of use. Now, patients are not required to take it with an antidepressant

and can use it as a standalone treatment. Today, in Fort Worth, Texas, Sean Fury will do what he does every Friday. He and his wife will get into the car and drive 10 minutes to the clinic where he takes Spravato. He'll inhale the medication through his nose and then relax in a reclining chair for two hours. Sean told me that now he's hopeful for the future. He's finished filming his vampire movie and is editing it. He sent us a clip from the final scene.

The dialogue is almost verbatim, a conversation he had with his wife at the depths of his depression. She's so tired, Shar. Down to my core, it's just, I have nothing left. It's all right. I have plenty.

Does it have a title? Yes, it's called The Hard Way. I have plenty. Does it have a title? Yes, it's called The Hard Way. The Hard Way? Yep. It seems like a very apt title. Yes. Hopefully it'll be ready by April, May, to start a festival run. I really want to get it in front of as many audiences as possible to

show them that, you know, people struggling with the same demons I've been struggling with, those things can be fought. You don't have to just sit with it. And so I want to get that message to as many people as possible. Well, Sean, thank you so much for your time. Well, thank you, Jess. It's been a pleasure talking to you as well. as well. Before we go, if you're considering self harm, help is available. Call the Suicide and Crisis Lifeline by texting or dialing 988. That's 988.

That's all for today, Friday, March 21st. The Journal is a co-production of Spotify and The Wall Street Journal. The show is made by Catherine Brewer, Pia Gadkari, Rachel Humphreys, Sophie Cotner, Ryan Knutson, Matt Kwong, Kate Linebaugh, Colin McNulty, Annie Minoff, Laura Morris, Enrique Perez de la Rosa, Sarah Platt, Alessandra Rizzo, Alan Rodriguez Espinosa, Heather Rogers, Piers Singie, Jeevika Verma, Lisa Wang, Catherine Whalen, Tatiana Zemice, and me, Jessica Mendoza, with help from Trina Menino. Our engineers are Griffin Tanner, Nathan Singapok, and Peter Leonard. Our theme music is by So Wiley. Additional music this week from

Katherine Anderson, Peter Leonard, Bobby Lord, Nathan Singapok, Griffin Tanner, and Blue Dot Sessions. Fact Checking this week by Najwa Jamal and Mary Mathis. Thanks for listening. See you on Monday.