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

Speaker 1 A quick heads up before we get started. This episode mentions suicide and discusses depression.
Please listen with care.

Speaker 1 So, just to start us off, could you introduce yourself, your name, your age, what you do?

Speaker 2 My name is Sean Fury. I am a writer in Fort Worth, Texas.
I'm 36 years old.

Speaker 1 And I'm seeing some,

Speaker 1 like, a very interesting background there for you. You've got a poster.

Speaker 2 You've got, is that creature from the black lagoon it is that's that's my favorite sean loves movies but he doesn't just love to watch them he makes them too horror's my go-to um 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 uh you know to to kind of work through my own issues with um

Speaker 2 that depression and anxiety, PTSD.

Speaker 2 And I chose a vampire type story because I feel like there are times times where I felt really low where I just feel like I'm sucking the life out of my family, my wife.

Speaker 2 Yeah, so I decided to make that literal and explore it through a vampire film.

Speaker 1 Sean says depression has been part of his life for as long as he can remember. At times, he says, it's been debilitating.

Speaker 2 There are days where my wife has to physically help me out of bed. I just can't get up.

Speaker 2 I can't really bear to face the day.

Speaker 1 What kind of treatments have you tried over time?

Speaker 2 Pretty much anything that came onto the market,

Speaker 2 I tried. And it is hard because you start taking it and you don't notice if it works or not for a couple weeks.

Speaker 2 And then by that point, you have to kind of wean yourself off of it to try something new.

Speaker 2 And in the meantime, those antidepressants can have several side effects on your body, which are frustrating as well.

Speaker 1 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 Spravado, and it's made by Johnson ⁇ Johnson.

Speaker 1 And Spravato is unique because it's a derivative of ketamine, best known as an illicit club drug.

Speaker 1 What impact has Spravado had on your life? How would you describe that?

Speaker 2 Oh, man.

Speaker 2 I still have outlier days, but I am so much more positive and so much able

Speaker 2 to better roll with the punches just of life.

Speaker 2 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?

Speaker 1 Patients with results like Sean's have propelled sales of Spravado. Last year, it exceeded a billion dollars in sales worldwide.
becoming a blockbuster drug for J and J.

Speaker 1 For the pharmaceutical industry, it's amplifying the potential of psychedelics as a treatment for mental health.

Speaker 1 Welcome to The Journal, our show about money, business, and power. I'm Jessica Mendoza.
It's Friday, March 21st.

Speaker 1 Coming up on the show: How a ketamine-derived treatment for depression became a hit for Johnson Johnson.

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Speaker 1 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.

Speaker 1 But even though depression is so prevalent and in recent years more widely discussed, the way we treat it hasn't evolved for years.

Speaker 1 Why is depression so hard to treat?

Speaker 4 Yeah, I think that's a very 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.

Speaker 1 Husseini Manji is a neuroscientist and professor of psychiatry at Oxford University. And for years, he worked at J ⁇ J coming up with treatments for depression.

Speaker 4 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.

Speaker 4 So there's a real need to come up with improved treatments.

Speaker 1 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.

Speaker 5 Prozac Weekly is here.

Speaker 6 Ask your doctor if it's right for you.

Speaker 1 And Zoloft.

Speaker 7 Zoloft. When you know more about what's wrong, you can help make it right.

Speaker 1 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.

Speaker 4 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.

Speaker 4 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.

Speaker 4 Ultimately, you need to bring about other changes, which results in people getting better.

Speaker 1 Husseini wanted a medicine that worked quickly and could help people with treatment-resistant depression.

Speaker 1 Instead of boosting serotonin levels, he thought a better strategy for dealing with depression was to help the brain cells create new connections.

Speaker 1 So Husseini went looking for a substance that could do that, and he found a good option, ketamine.

Speaker 1 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.

Speaker 9 Ketamine, known on the streets as special K, vitamin K, or cat valium, a street drug police say is starting to resurface.

Speaker 6 It is usually snorted or swallowed. The desired effect is euphoria, a dreamlike state.

Speaker 1 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.

Speaker 4 So I was involved in some of the earlier studies using intravenous ketamine and those studies really showed remarkable effects.

Speaker 4 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.

Speaker 1 In 2008, Husseini was hired to become the new global head of neuroscience at JNJ. He started working to create an effective medication for treatment-resistant depression.

Speaker 1 Husseini believed ketamine could provide a breakthrough. But first, he needed to convince JNJ.

Speaker 4 When I first brought up the idea, I think understandably people had some reservations because, you know, ketamine has sometimes been used as a club drug. So I had to really,

Speaker 4 you know, sort of walk through a lot of the reasons why I thought this would be successful.

Speaker 1 How long before you were able to change their minds? Did it take a lot of arguing on your part?

Speaker 4 Yeah,

Speaker 4 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.

Speaker 1 Knowing these these risks, Husseini and his team worked on minimizing them as much as possible.

Speaker 1 He came up with the idea of putting a very small amount of a derivative of ketamine into a nasal spray device.

Speaker 4 It's like an inhaler, except it's, you know, delivered to the nose. Basically, the person comes into the clinic, their dose is calculated, and they self-administer it.

Speaker 4 So they administer it in the nose themselves, and then there's no drug left in the device, so you throw away the device.

Speaker 1 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.

Speaker 1 What were the challenges of testing this drug on patients? What were the risks involved?

Speaker 4 Sure. So it's basically two side effects.

Speaker 4 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.

Speaker 4 The second thing is something called dissociation.

Speaker 4 So what dissociation is that you might feel that the colors around you are brighter or the sounds are louder, etc.

Speaker 4 For almost everyone, you know, it sort of starts within about half an hour. At about one hour, it's gone.

Speaker 1 Dissociation, is that like tripping?

Speaker 4 I think it's a low-level tripping.

Speaker 8 Very low-level tripping.

Speaker 4 Very low-level tripping.

Speaker 1 Because of these side effects, the drug would have to be administered under medical supervision in a clinic.

Speaker 1 In testing, Husseini and his team saw real results.

Speaker 1 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.

Speaker 1 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.

Speaker 1 In 2019, the FDA approved Spravado for patients with treatment-resistant depression to take along with another antidepressant.

Speaker 10 All new tonight, a controversial new treatment for depression. The FDA approved the antidepressant this week, and it's a nasal spray.

Speaker 11 Spravado is the first new type of depression treatment since Prozac was okayed back in 1987.

Speaker 1 At the time, JNJ put the list price for Spravado between $590 and $885 per treatment session.

Speaker 1 For Husseini and his team, the FDA approval was a huge breakthrough.

Speaker 4 You know, we got the call while the whole team was together, and obviously we celebrated right after.

Speaker 1 Were you popping champagne?

Speaker 4 It wasn't quite champagne, but

Speaker 8 we were really happy. Okay.

Speaker 1 But Spravado 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.

Speaker 1 And then the pandemic made that sort of in-person treatment even harder.

Speaker 1 How Spravado turned into a blockbuster is next.

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Speaker 1 When you first heard about a ketamine treatment for depression, what did you think?

Speaker 2 I associated it, ketamine, with like micro-dosing LSD, which I was very nervous, hesitant to try.

Speaker 2 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.

Speaker 1 Sean Fury, who we heard from earlier, was encouraged to try spravado by his psychiatrist because he was continuing to struggle with his depression.

Speaker 1 What changed your mind?

Speaker 2 I think I just, I got, it got so bad

Speaker 2 having, you know, suicidal thoughts and all of that. And I think finally I just hit a breaking point where I was like, okay, well, we'll try Spravado

Speaker 2 and see how that goes. At that point, I felt like maybe I didn't have anything to lose.

Speaker 1 Sean attended his first appointment in 2023. The treatment was covered by his insurance.
How did that first session leave you feeling afterwards?

Speaker 2 It was very jarring. I remember being

Speaker 2 surprised and nervous and wondering if this was something I wanted to keep doing, if it was going to be like this every time.

Speaker 1 But Sean went back the next week and the next and the next.

Speaker 1 And how did your body feel after taking it?

Speaker 2 The first

Speaker 2 probably 40 minutes, I feel it the most. You feel

Speaker 2 lighter, you know, you get like tingling sensations a bit.

Speaker 2 I let my mind just kind of wander

Speaker 2 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.

Speaker 2 There are some days where I come home and immediately take a nap just because I'm...

Speaker 2 just tapped out and there are other days where I'm ready to go.

Speaker 1 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.

Speaker 2 Even though they had told me about it, I was not prepared at all for that. I remember that being very scary.

Speaker 2 And thankfully, my wife is there at the treatments with me and so she was holding my hand and talking to me through it.

Speaker 2 Because when I'm taking this bravado, that feeling that I get is kind of being somewhere between reality reality and dreaming.

Speaker 2 So your mind's going a million miles an hour, but you can still hear what's going on

Speaker 2 around you.

Speaker 2 And that was very jarring at first.

Speaker 1 But overall, Sean says spravado has worked for him.

Speaker 2 I could handle things better than I could before I had started taking spravado. Just like the daily stresses of life.

Speaker 2 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.

Speaker 2 I felt like the shell had broken and I was able to finally kind of breathe again.

Speaker 2 The biggest thing is

Speaker 2 that I recognize when I'm having those negative thoughts, which before I used to,

Speaker 2 it never even occurred to me that I was kind of spiraling into this

Speaker 2 cycle of negativity and kind of self-abuse.

Speaker 2 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,

Speaker 2 the most powerful change to me.

Speaker 1 Since its slow start, Spravado has steadily grown its sales. JJ offered assistance to doctors who were interested in setting up clinics like the one Sean goes to.

Speaker 1 And like so many pharma companies, JJ also invested in an ad campaign.

Speaker 12 With fewer depression symptoms, you may begin to feel like yourself again.

Speaker 12 Ask your doctor about Spravado.

Speaker 1 Since the beginning of 2023, prescriptions for Spravado have nearly doubled in the U.S. to more than 46,000.

Speaker 1 But with an estimated 3 to 5 million people suffering from treatment-resistant depression, according to JNJ, the company has high hopes for the drug's potential.

Speaker 1 JNJ predicts that it could make them $5 billion annually. Here's a company executive from an earnings call in January.

Speaker 1 And Spravato 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.

Speaker 1 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.

Speaker 1 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.

Speaker 1 The FDA considered approving MDMA for treating PTSD, a condition that affects 13 million Americans. But the agency decided that drug needed more testing.

Speaker 1 Hosseini, who has now left JNJ, told me he thinks that the success of Spravato could mean we see other non-traditional drugs being used as treatments.

Speaker 4 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.

Speaker 4 So I think that's one of the things that until Spravado came along, that simply wasn't the case. So I think it certainly has opened the door.

Speaker 1 But there are still unanswered questions about the future for patients taking Spravato.

Speaker 1 A JNJ 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.

Speaker 1 I spoke to one psychiatrist who runs a spravado clinic, and he raised some concerns about patients taking the drug beyond six years. I asked Husseini about this.

Speaker 1 Would you say spravado is a long-term or a short-term treatment?

Speaker 4 I would say probably it'll depend on

Speaker 4 you know, 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, you know, they've got bad illness.

Speaker 1 If they're not on treatment the illness might come back in January the FDA went one step further in its approval of spravado 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

Speaker 1 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 spravado he'll inhale the medication through his nose and then relax in a reclining chair for two hours.

Speaker 1 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.

Speaker 1 The dialogue is almost verbatim, a conversation he had with his wife at the depths of his depression.

Speaker 5 She's so tired, Sharp.

Speaker 2 Down to my core, it's just

Speaker 1 I have nothing left.

Speaker 1 It's alright.

Speaker 1 I've played it.

Speaker 1 Does it have a title?

Speaker 2 Yes, it's called The Hard Way.

Speaker 8 The Hard Way. Yeah.

Speaker 1 It seems like a very apt title.

Speaker 2 Yes. Hopefully, it'll be ready by April, May to start a festival run.

Speaker 2 I really want to get it in front of as many audiences as possible to

Speaker 2 show them that people struggling with the same demons I've been struggling with, those things can be fought.

Speaker 2 You don't have to just sit with it. And so I want to get that message to as many people as possible.

Speaker 1 Well, Sean, thank you so much for your time.

Speaker 2 Well, thank you, Jess. It's been a pleasure talking to you as well.

Speaker 1 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.

Speaker 1 That's all for today, Friday, March 21st. The journal is a co-production of Spotify and the Wall Street Journal.
Additional reporting in this episode by Peter Loftus.

Speaker 1 The show is made by Katherine Brewer, Pia Gakkari, Rachel Humphreys, Sophie Codner, Ryan Knutson, Matt Kwong, Kate Leinbaugh, Colin McNulty, Annie Minoff, Laura Morris, Enrique Perez-De La Rosa, Sarah Platt, Alessandra Rizzo, Alan Rodriguez-Espinosa, Heather Rogers, Pierce Singhi, Jivaca Verma, Lisa Wang, Catherine Whalen, Tatiana Zemis, and me, Jessica Mendoza, with help from Trina Menino.

Speaker 1 Our engineers are Griffin Tanner, Nathan Singap, and Peter Leonard. Our theme music is by So Wiley.

Speaker 1 Additional music this week from Katherine Anderson, Peter Leonard, Bobby Lorde, Nathan Singapock, Griffin Tanner, and Blue Dot Sessions. Fact checking this week by Najwor Jamal and Mary Mathis.

Speaker 1 Thanks for listening. See you on Monday.