--:-- [Theme music fades out]
--:-- Jessica Mendoza: Welcome to The Journal, our show about money, business, and power. I'm Jessica Mendoza. It's Friday, March 21st.
--:-- [Soft music continues in the background]
--:-- Jessica Mendoza: Before we get started, a quick heads up. This episode mentions suicide and discusses depression. Please listen with care.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: So, just to start us off, could you introduce yourself, your name, your age, what you do?
--:-- Sean Fury: My name is Sean Fury. I'm a writer in Fort Worth, Texas. I'm 36 years old.
--:-- Jessica Mendoza: And I'm seeing a very interesting background there for you. You've got a poster. You've got, is that Creature from the Black Lagoon?
--:-- Sean Fury: It is. That's my favorite.
--:-- Jessica Mendoza: Sean loves movies, but he doesn't just love to watch them. He makes them, too. Horror is my go-to.
--:-- Sean Fury: We just finished the first leg of a shoot of a horror thriller. It's a vampire film.
--:-- Jessica Mendoza: Why did you want to make this film?
--:-- Sean Fury: 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.
--:-- Jessica Mendoza: Yeah, so I decided to make that literal and explore it through a vampire film.
--:-- Sean Fury: 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.
--:-- Jessica Mendoza: What kind of treatments have you tried over time?
--:-- Sean Fury: 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 weeks. And then by that point you have to kind of wing 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.
--:-- Jessica Mendoza: 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.
--:-- Sean Fury: And it's unique because it's a derivative of ketamine, best known as an illicit club drug.
--:-- Jessica Mendoza: What impact has Spravato had on your life? How would you describe that?
--:-- Sean Fury: 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?
--:-- [Soft music continues in the background]
--:-- Jessica Mendoza: 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.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: For the pharmaceutical industry, it's amplifying the potential of psychedelics as a treatment for mental health.
--:-- Jessica Mendoza: 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 a ketamine-derived treatment for depression became a hit for Johnson & Johnson.
--:-- [Soft music continues in the background]
--:-- Jessica Mendoza: We'll be right back.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: Spending millions of dollars. I'm so excited to embark on this adventure with all of you. Make the best I do win! On brand with Jimmy Fallon. Series premiere Tuesday on NBC.
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--:-- [Pause for a moment]
--:-- Jessica Mendoza: Nearly 30% of adults in the U.S. say they've been diagnosed with depression at some point in their lives, according to a Gallup survey.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: 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?
--:-- [Pause for a moment]
--:-- Dr. Hosseini Manji: 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.
--:-- Jessica Mendoza: Dr. Hosseini 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.
--:-- Dr. Hosseini Manji: 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.
--:-- Jessica Mendoza: 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.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: 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.
--:-- [Pause for a moment]
--:-- Dr. Hosseini Manji: 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.
--:-- [Pause for a moment]
--:-- Dr. Hosseini Manji: 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.
--:-- Jessica Mendoza: 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.
--:-- [Pause for a moment]
--:-- Dr. Hosseini Manji: Hosseini 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.
--:-- Jessica Mendoza: So Hosseini went looking for a substance that could do that. And he found a good option. Ketamine.
--:-- [Pause for a moment]
--:-- Dr. Hosseini Manji: 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.
--:-- Jessica Mendoza: 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.
--:-- [Pause for a moment]
--:-- Dr. Hosseini Manji: 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.
--:-- Jessica Mendoza: So I was involved in some of the earlier studies using intravenous ketamine, and those studies really showed remarkable effects.
--:-- [Pause for a moment]
--:-- Dr. Hosseini Manji: 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.
--:-- Jessica Mendoza: 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.
--:-- [Pause for a moment]
--:-- Dr. Hosseini Manji: In 2008, Hosseini 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.
--:-- Jessica Mendoza: Hosseini believed ketamine could provide a breakthrough. But first, he needed to convince J&J.
--:-- [Pause for a moment]
--:-- Dr. Hosseini Manji: 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.
--:-- Jessica Mendoza: So I had to really, you know, sort of walk through a lot of the reasons why I thought this would be successful.
--:-- [Pause for a moment]
--:-- Dr. Hosseini Manji: 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.
--:-- Jessica Mendoza: Knowing these risks, Hosseini 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.
--:-- [Pause for a moment]
--:-- Dr. Hosseini Manji: 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.
--:-- Jessica Mendoza: So they administer it in the nose themselves, and then there's no drug left in the device, so you throw away the device.
--:-- [Pause for a moment]
--:-- Dr. Hosseini Manji: 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.
--:-- Jessica Mendoza: What were the challenges of testing this drug on patients? What were the risks involved?
--:-- [Pause for a moment]
--:-- Dr. Hosseini Manji: 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.
--:-- Jessica Mendoza: 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, etc.
--:-- [Pause for a moment]
--:-- Dr. Hosseini Manji: For almost everyone, you know, it sort of starts within about half an hour. At about one hour, it's gone.
--:-- Jessica Mendoza: Dissociation, is that like tripping?
--:-- Dr. Hosseini Manji: I think it's a low-level tripping. Very low-level tripping.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: Because of these side effects, the drug would have to be administered under medical supervision in a clinic.
--:-- Jessica Mendoza: In testing, Hosseini 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.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: 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.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: In 2019, the FDA approved Spravato for patients with treatment-resistant depression to take along with another antidepressant.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: 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 okayed back in 1987.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: At the time, J&J put the list price for Spravado between $590 and $885 per treatment session.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: For Hosseini and his team, the FDA approval was a huge breakthrough.
--:-- [Pause for a moment]
--:-- Dr. Hosseini Manji: You know we got the call while the whole team was together and obviously we celebrated right after.
--:-- Jessica Mendoza: Were you popping champagne?
--:-- Dr. Hosseini Manji: It wasn't quite champagne, but we were really happy.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: 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.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: And then the pandemic made that sort of in-person treatment even harder.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: How Spravado turned into a blockbuster is next.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: Mint is still $15 a month for premium wireless. And if you haven't made the switch yet, here are 15 reasons why you should.
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--:-- [Pause for a moment]
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--:-- [Pause for a moment]
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--:-- [Pause for a moment]
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--:-- [Pause for a moment]
--:-- Jessica Mendoza: When you first heard about a ketamine treatment for depression, what did you think?
--:-- [Pause for a moment]
--:-- Sean Fury: I associated it with like micro dosing 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.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: Sean Fury, who we heard from earlier, was encouraged to try Spravato by his psychiatrist because he was continuing to struggle with his depression.
--:-- [Pause for a moment]
--:-- Sean Fury: What changed your mind?
--:-- [Pause for a moment]
--:-- Sean Fury: 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.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: At that point, I felt like maybe I didn't have anything to lose.
--:-- [Pause for a moment]
--:-- Sean Fury: Sean attended his first appointment in 2023. The treatment was covered by his insurance.
--:-- [Pause for a moment]
--:-- Sean Fury: How did that first session leave you feeling afterwards?
--:-- [Pause for a moment]
--:-- Sean Fury: 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.
--:-- [Pause for a moment]
--:-- Sean Fury: But Sean went back the next week, and the next, and the next.
--:-- [Pause for a moment]
--:-- Sean Fury: And how did your body feel after taking it?
--:-- [Pause for a moment]
--:-- Sean Fury: The first probably 40 minutes, I feel it the most. You feel lighter. You know, you get like tingling sensations a bit.
--:-- [Pause for a moment]
--:-- Sean Fury: I let my mind just kind of wander. And it wears off after about 40 or 50 minutes or so.
--:-- [Pause for a moment]
--:-- Sean Fury: And that second hour is just trying to be calm.
--:-- [Pause for a moment]
--:-- Sean Fury: 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.
--:-- [Pause for a moment]
--:-- Sean Fury: And there are other days where I'm ready to go.
--:-- [Pause for a moment]
--:-- Sean Fury: In the two years he's been taking it, Sean says he's only experienced hallucinations twice.
--:-- [Pause for a moment]
--:-- Sean Fury: He told me about the first time it happened.
--:-- [Pause for a moment]
--:-- Sean Fury: Even though they had told me about it, I was not prepared at all for that.
--:-- [Pause for a moment]
--:-- Sean Fury: I remember that being very scary.
--:-- [Pause for a moment]
--:-- Sean Fury: Thankfully, my wife is there at the treatments with me, and so she was holding my hand and talking to me through it.
--:-- [Pause for a moment]
--:-- Sean Fury: Because when I'm taking the Spravato, that feeling that I get is kind of being somewhere between reality and dreaming.
--:-- [Pause for a moment]
--:-- Sean Fury: So your mind's going a million miles an hour, but you can still hear what's going on around you.
--:-- [Pause for a moment]
--:-- Sean Fury: And that was very jarring at first.
--:-- [Pause for a moment]
--:-- Sean Fury: But overall, Sean says Spravato has worked for him.
--:-- [Pause for a moment]
--:-- Sean Fury: I could handle things better than I could before I'd started taking Spravato.
--:-- [Pause for a moment]
--:-- Sean Fury: So 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.
--:-- [Pause for a moment]
--:-- Sean Fury: My confidence came back to some extent.
--:-- [Pause for a moment]
--:-- Sean Fury: I felt like the shell had broken and I was able to finally kind of breathe again.
--:-- [Pause for a moment]
--:-- Sean Fury: 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 and kind of self-abuse.
--:-- [Pause for a moment]
--:-- Sean Fury: Um, when that starts happening now I I recognize it pretty much right away and I'm able to kind of ground myself or redirect my thoughts.
--:-- [Pause for a moment]
--:-- Sean Fury: And that's been the biggest change, the most powerful change to me.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: Since its slow start, Spravato has steadily grown its sails.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: J offered assistance to doctors who were interested in setting up clinics like the one Sean goes to.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: And like so many pharma companies J also invested in an ad campaign.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: With fewer depression symptoms, you may begin to feel like yourself again. Ask your doctor about Spravato.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: Since the beginning of 2023, prescriptions for Spravato have nearly doubled in the U.S. to more than 46,000.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: 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.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: J&J predicts that it could make them $5 billion annually.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: Here's a company executive from an earnings call in January.
--:-- [Pause for a moment]
--:-- Company Executive: And Spravato's also the only antidepressant to ever receive breakthrough designation from the FDA.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: So great momentum and a long-term commitment to patients suffering with depression.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: Spravato's success shows the challenges and opportunities for big pharma when it comes to mental health treatments.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: And it's also giving hope to companies working in the field of psychedelic research.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: There are now dozens of startups studying the effects of drugs like LSD and psilocybin on mental health.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: And last year, the industry seemed poised for another breakthrough.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: The FDA considered approving MDMA for treating PTSD, a condition that affects 13 million Americans.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: But the agency decided that drug needed more testing.
--:-- [Pause for a moment]
--:-- Dr. Hosseini Manji: I think there's no doubt it's opened the door.
--:-- [Pause for a moment]
--:-- Dr. Hosseini Manji: 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.
--:-- [Pause for a moment]
--:-- Dr. Hosseini Manji: So I think that's one of the things that until Spravato came along, that simply wasn't the case.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: So I think it certainly has opened the door.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: But there are still unanswered questions about the future for patients taking Spravato.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: 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.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: I spoke to one psychiatrist who runs a Spravato clinic, and he raised some concerns about patients taking the drug beyond six years.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: I asked Hussaini about this.
--:-- [Pause for a moment]
--:-- Dr. Hosseini Manji: Would you say Spravato is a long-term or a short-term treatment?
--:-- [Pause for a moment]
--:-- Dr. Hosseini Manji: I would say probably it'll depend on the indication.
--:-- [Pause for a moment]
--:-- Dr. Hosseini Manji: 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.
--:-- [Pause for a moment]
--:-- Dr. Hosseini Manji: So if they're not on treatment, the illness might come back.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: Today, in Fort Worth, Texas, Sean Fury will do what he does every Friday.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: He and his wife will get into the car and drive 10 minutes to the clinic where he takes Spravato.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: He'll inhale the medication through his nose and then relax in a reclining chair for two hours.
--:-- [Pause for a moment]
--:-- Sean Fury: Sean told me that now he's hopeful for the future.
--:-- [Pause for a moment]
--:-- Sean Fury: He's finished filming his vampire movie and is editing it.
--:-- [Pause for a moment]
--:-- Sean Fury: He sent us a clip from the final scene.
--:-- [Pause for a moment]
--:-- Sean Fury: The dialogue is almost verbatim a conversation he had with his wife at the depths of his depression.
--:-- [Pause for a moment]
--:-- Sean Fury: She's so tired, Char. Down to my core, it's just... I have nothing left.
--:-- [Pause for a moment]
--:-- Sean Fury: It's alright. I have plenty.
--:-- [Pause for a moment]
--:-- Sean Fury: Does it have a title?
--:-- [Pause for a moment]
--:-- Sean Fury: Yes, it's called The Hard Way.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: The Hard Way?
--:-- [Pause for a moment]
--:-- [Pause for a moment]
--:-- Jessica Mendoza: It seems like a very apt title.
--:-- [Pause for a moment]
--:-- [Pause for a moment]
--:-- Jessica Mendoza: Hopefully it'll be ready by April, May, to start a festival run.
--:-- [Pause for a moment]
--:-- Sean Fury: I really want to get in front of as many audiences as possible to show them that people struggling with the same demons I've been struggling with, those things can be fought.
--:-- [Pause for a moment]
--:-- Sean Fury: You don't have to just sit with it.
--:-- [Pause for a moment]
--:-- Sean Fury: And so I want to get that message to as many people as possible.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: Well, Sean, thank you so much for your time.
--:-- [Pause for a moment]
--:-- Sean Fury: Well, thank you, Jess. It's been a pleasure talking to you as well.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: 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.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: That's all for today, Friday, March 21st.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: The Journal is a co-production of Spotify and The Wall Street Journal.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: Additional reporting in this episode by Peter Loftus.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: The show is made by With help from Trina Menino.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: Our engineers are Griffin Tanner, Nathan Singapok, and Peter Leonard.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: Our theme music is by So Wiley.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: Additional music this week from Katherine Anderson, Peter Leonard, Bobby Lord, Nathan Singapok, Griffin Tanner, and Blue Dot Sessions.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: Fact-checking this week by Najwa Jamal and Mary Mathis.
--:-- [Pause for a moment]
--:-- Jessica Mendoza: Thanks for listening. See you on Monday.
--:-- [Theme music fades in]
