Nasal Spray for Depression? Not So Fast

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Last week, the FDA advisory committee endorsed Janssen Pharmaceutical’s (division of Johnson & Johnson) experimental nasal spray for depression despite a mixed bag of clinical trial results. The panel voted 14-2 to approve Esketamine nasal spray for major depression in patients who have NOT benefited from two or more antidepressants (e.g., Prozac, Paxil, or Zoloft).

This fast-acting nasal spray using esketamine is a chemical mirror image of the anesthetic ketamine, which is often used by veterinarians to sedate animals but is also a schedule III drug known on the street as “Special K” — thanks to its dissociative and hallucinogenic effects.

This new drug was designed in an effort to help the millions of people who suffer from persistent depression and do not respond to current antidepressant products. The nasal spray is seen as a potential substantial improvement over existing therapies for “Treatment Resistant Depression” (TRD), considered a serious or life-threatening condition.

In theory, a drug that provides rapid relief within 24 hours vs the standard 4-6 weeks for the current antidepressants on the market sounds good. However, the disease label of “Treatment Resistant Depression” (TRD) is also the new buzzword allowing drug companies to obtain FDA fast tracking or “breakthrough therapy” designation without having to go through more rigorous testing protocols. Such designation gives the pharmaceutical company the ability to present smaller, fewer clinical trials in order to get their drug to market quicker. While most approved antidepressants currently on the market had to show effectiveness data from at least two positive short-term trials, Janssen only presented one positive short-term trial and the second is an incomplete picture as it is from a withdrawal trial. Janssen’s other trials failed to meet their primary endpoints for efficacy. Additionally, there were also clinical trial participant suicides that occurred during the clinical trials, however these were glossed over and presented as unrelated to the “study” drug. In my opinion, we need more information on the potential link to suicide before an assumption can be made that it’s safe.

Despite all of this, several members of the FDA Advisory Committee perceived this new drug as a potential “game changer” in the way depression is treated. I, however, am NOT one of them. I take my role as the Consumer Representative very seriously and want to make sure that any pharmaceutical drug that the FDA approves shows greater benefit than potential harm. There are real world implications once these drugs are approved and, on the market, advertised with an FDA stamp of approval on them, and counted on without question by the doctors prescribing them and the potential millions of people who will take them.

Too many times I have seen that as soon as one of these controversial drugs gets approved, the drug company’s PR and advertising machine immediately kicks into hyperdrive. The media will be given talking points and tout it as a “breakthrough” treatment for depression that works within mere hours of inhaling the drug, and people will start lining up at their doctor’s offices. In fact, just a day after this meeting, news of this meeting and drug was all over the national media appealing to America’s “quick fix” culture. This “breakthrough treatment” messaging is powerful, especially in the environment of rising antidepressant prescription rates and increased suicides. The media needs to do a better job of questioning these FDA approvals and not just report the “promising” findings off a drug company press release.

Another observation I have had lately is that a majority of new drug application reviews are coming before the FDA Advisory Committees with a Risk Evaluation Mitigation Strategies (REMS) program. The Food and Drug Administration Amendments Act of 2007 gave the FDA authority to require a REMS for certain medications with serious safety concerns to help ensure the benefits of the medication outweigh its risks. REMS are not designed to mitigate adverse events of a medication, rather, it focuses on preventing, monitoring and/or managing a specific serious risk by informing, educating and/or reinforcing actions to reduce the frequency and/or severity of the event.

I believe most of the FDA Advisory Committee members vote for these controversial drugs assuming that the REMS program will address any of their potential safety concerns. What they fail to realize is that the REMS program is not enforceable and the drug companies are responsible for managing and reporting to the FDA. I can NOT in good faith cross my fingers and trust the drug companies and FDA to do what they say they will do, just to get the drug approved.

At the end of the day, safety will always be my top priority and I didn’t feel this was similarly the case for the manufacturer as it rushed this esketamine nasal spray to market. I cannot vote for something when the perceived benefits do not clearly and demonstrably outweigh the potential for known harms such as sedation, dissociation, and long-term cognitive or memory loss — this is especially so considering the extremely limited positive clinical trial results.

At one time, the current antidepressants were seen as “game changers” beginning with the launch of Prozac in the late 1980s. Little did the medical establishment and general public know then what we clearly now know today about the questionable efficacy of antidepressants and all the associated dangers such as suicides and withdrawal issues that come with taking these medicines. It is in the rush to market without sound clinical testing and trials that prove efficacy, without potential horrible side effects or outcomes, that we set society up for misuse of medical drugs and create the very real potential for heartache and disappointment for many.

Time will tell, but as I always say, we (the American public) are the real clinical trial. We pay the ultimate price for the lowering of FDA standards for drug approvals.

***

Mad in America hosts blogs by a diverse group of writers. These posts are designed to serve as a public forum for a discussion—broadly speaking—of psychiatry and its treatments. The opinions expressed are the writers’ own.

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59 COMMENTS

  3. Based on how little testing is required for “regular” FDA approved psychiatric drugs, it seems Esketamine can be considered virtually UNtested. Even more worrisome, this drug will inevitably be prescribed to young children and teenagers –off label. Parents are desperate to help their kids, and when (as often happens) the Prozac and Risperdal cocktails don’t work, they may acquiesce to this ‘nasal spray for depression.’

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    • It isn’t designed as first line treatment for depression. Has anyone done any research before posting comments about this? No child is going to get some C-III substance nasal spray for their depression. It is meant for those that have tried other things and they have failed, as well as for people with suicidal ideation. It isn’t something being designed to be just given to kids for off label use. Those kinds of doctors who would do such a thing are the real problem here.

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  4. Thanks for this. I found your personal story compelling. I am sorry for your loss.
    Back in the day in treatment with children, no medication was used. Even in residential treatment. The only time I saw it used was for developer mentally disabled children and that was NOT across the board.
    It is not only chemicals that are issued as treatment but the total disabandement of any concept of treatment quality. If there was any and I still believe in some places or folks there were , it has become extinct. What is left is the last visible skeleton of so called treatment and a continuing ongoing assault of bio0sychiatry to keep its hands on the money at all costs.
    Thanks again and THANKS for commenting.

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  5. “Depression is still the Great Enemy. More personal energy is expended in manic defenses against, diversions from, and denial of it than goes into any other supposed psychopathological threat to society.”

    “Yet through depression we enter depths and in depths find soul. Depression is essential to the tragic sense of life. It moistens the dry soul, and dries the wet. It brings refuge, limitation, focus, gravity, weight, and humble powerlessness. It reminds of death. The true revolution begins in the individual who can be true to his or her depression. Neither jerking oneself out of it, caught in cycles of hope and despair, nor suffering it through till it turns, nor theologizing it – but discovering the consciousness and depth it wants. So begins the revolution in behalf of soul.”

    James Hillman

    I can’ t see problem in state of the depression, but in people who are searching for a medical cure.
    To cure means to accept, to believe -TO BELIEVE IN PSYCHOLOGICAL SUFFERING. There is no cure if we show hate toward depression. And that hate is purely egoic or theological.
    Apollonians knows nothing about psyche, but still they want to make money on psychological man.

    To search for medical cure means that no one believe in the depression per se. This is unreal for happy people. They want to lock you up, because of their hatred and lack of time to be with someone beyond naive apollonnian archetype.
    Psyche is the truth, depression is the truth, and mental health is when your ego is too naive, and to far from psychological reality, and death. Mental health is psychological naivety. And depression and psychosis are psychological awareness.

    DO WE UNDERSTAND “MENTAL HEALTH” DEFINITION, PROPERLY? No.

    They want to cure someone form something which is not a medical issue. There is no virus of depression, to get rid of, so they will get rid of human being.

    For “biological” psychiatry, human being is a pathogen.
    We must remember that apollonic society (the ego in the center of the psychological reality) is not a psychological society, it is material and fake like plastic. Resurrection of the psyche is needed.

    James Hillman “Re – Visioning psychology”. .

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    • Anyone can become situationally depressed. Is esketamine designed for situational depression? No it is not. Are some people abused and traumatized by horrible experiences in life? Unfortunately, yes there are, and sometimes these people are never given a chance to develop normal coping mechanisms in life and develop major depressive disorders and suicidal ideation. These are not normal states of mind, and no, they are not biological in origin. This is not some virus that esketamine is meant to eliminate.

      Some people are in deep moral black holes and/or develop into broken human beings with such horrible depression that suicide seems an option to deal with it. Getting these people to just “snap out of it” and realize that they can just change their own mental states by relearning their cognitive behaviors and emotional responses to trauma and abuse is quite difficult. Some people truly cannot get out of bed, let alone have the desire to go to a mental hospital for help.

      I know psych meds are mostly neurotoxic things, but sometimes there are people who need a stepping stone or crutch to just be able to get out of bed or out of a bad situation so they can get into proper therapy and learn to make lifestyle changes and all that, which people normally do without medication.

      Unfortunately, we cannot speak on behalf of those that are slashing their wrists because of abuse, neglect, trauma, rape, loss, shame, and/or defeat (yet so many people seem to think they can bc of their affluence and privilege in life that leads to the condemnation of the mentally inferior by merely stating that “if only they thought better, their lives would magically heal and all mental illness just vanish”).

      For anyone to write a book about how mental health is not a medical issue is just profiting by stating the obvious. No kidding it isn’t about any sort of virus of depression, as no such thing exists. The people who esketamine is designed to help are truly those that have tried things before that failed them as well as those that need a little artificial boost to get going on making lifestyle changes, if that is even possible.

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      • I think you are more than a bit optimistic about the intentions of the psychiatric profession when you say it’s obvious that “mental health is not a medical issue.” In fact, this is the song the profession has been singing loud and clear since the DSM III came out in 1980. Millions of the so-called “mentally ill” have been told by their doctors, their psychiatrists, the Oprah Winfrey show, TV shows and movies, and of course, those wonderful DTC advertisements showing Zoloft “rebalancing” the chemicals in our cartooned synapses while failing to mention the dramatic reduction of serotonin receptors that results from this supposed “balancing.” It is thus VERY far from “obvious” that “mental illnesses” are not biological entities. A few years back, over 80% of surveyed Americans believed that “low serotonin” causes depression, despite the fact that this idea was convincingly disproven by the mid 1980s.

        I’m glad you “get” that, but I don’t think you’re going to convince anyone that the psychiatric profession agrees with your assessment or shares it with their clientele in most cases.

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        • To be fair no psychiatrist ever told me that Steve.

          But numerous workers at the Mental Centers where these professionals work did. Countless supportive family members–the real brains–told us this at NAMI. Pete Earley admits this is a falsehood on his blog–can’t do links here–but says if it makes people take their “meds” it’s okay to lie.

          Yes the insulin is actually heroin. We can’t prove you have diabetes.But don’t you dare stop taking the white stuff. For rea$on$. 😛

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  6. I really appreciate the attention to this and agree that caution is warranted, but I’m also concerned about the particular bias you seem to be bringing to this issue. To characterize ketamine as “used by veterinarians” and “a party drug” just is not right and, to my eye, raises major concerns about credibility right out of the gate. It is a common and very effective ER anaesthetic, is also frequently used in hospice care, and has been shown over decades to be reliable and safe for these uses.

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    • Um, Daniel, ketamine IS used by veterinarians, and I’ve known it as a “party drug” called “Special K” for at least 2 decades now. (No, I’ve never used it myself, but have friends who have. They rave about it. Pun intended.) Ketamine was used in a clinical trial in Minn., where the “subjects” were actually recruited without their knowledge or consent. The cops would instruct ambulance staff to use it on persons who got rowdy in police custody, and were taken to the ER.
      I see no mention in the article about the crucial topic of DOSAGE. There’s also the issue of the “mirror molecule” aspect. My advanced neuro-chemistry and psychopharmacology degree is from a Cracker Jack box, so I can’t say what “mirror molecule” will really mean, when millions of persons of all ages use this drug in what is actually a LARGE-SCALE, MULTIPLE UNCONTROLLED & UNCONTROLLABLE VARIABLE FIELD TRIAL. In plain English, “let’s give a new drug to millions of people, and see what happens!” Hey, what could go wrong!?…. Your bias, Daniel, seems to be of the “some drugs are good, so more drugs are better” category. I’ll put MY trust with Kim Witczak…..

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      • YES we know ketamine is used by veterinarians, yet we as humans also use it in hospitals and hospice on other humans. To just dismiss anything having any medical value just because there are people who have used it recreationally or abused it pretty much dismisses everything out there right off the bat. Just take nasal spray right out of the market then. May as well pull benadryl as well as cough medicine like DXM. Holy cow, has anyone ever thought that maybe some people are self medicating with a substance and are not just hopeless addicts. OMG, there has been a huge amount of morphine addicts mostly since the Civil War began sending veterans home with it. May as well just discount morphine and all opioids due to millions of persons of all ages using this drug type, too.

        Ketamine itself is indeed used in ERs and hospitals, and I myself have gotten it in the operating room of a hospital.

        Daniel does NOT seem to be of the “some drugs are good, so more drugs are better” category. He just was stating that it is stupid to stereotype a drug based on its history in recreational use and not focusing on its medicinal value. And ketamine and esketamine are not identical substances!

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    • I don’t understand your problem with this woman raising the issues about ketamine since what she stated is absolutely true and has been true for at least the late 1970’s when I lived in New Orleans and heard people in the bars talking about Special K and how fun it was to take. Why would anyone in their right mind take a tranquilizer that’s made to be used for horses????????

      I believe that Bradford makes some really valid points about all this. I can’t imagine letting people loose with this stuff. I suspect that if it’s allowed to go to market that we’re going to see a lot more drug induced psychosis crop up on the scene and a lot more people making their way into the wonderful “mental hospitals” where they will be “diagnosed” as schizophrenic. This is absolutely stupid as hell. But it doesn’t surprise me one little bit as the drug companies continue to look for more and more avenues to increase their insane profits margin as they rape the people of this country in so many ways.

      Once again I will state that I do not see the FDA being the friend and protector of the American people.

      Thanks, but not thanks, I don’t want ketamine used on me if I end up in the hospital. Just because hospitals do something doesn’t necessarily mean that it’s good or safe. I was given a nice, big, whopping shot of fentanyl when I was last in the hospital. The nurse didn’t tell me what it was and I stupidly consented to take it without asking and the damned stuff depressed my oxygen levels and sent my blood pressure plummeting. An emergency doctor was summoned to Recovery where I was to attend to me. Just because hospitals do something doesn’t mean that it’s safe nor right. Remember, medicine is the third largest killer of Americans today.

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      • Good idea, Steve. When you’re “diagnosed” by such means when freaking on ketamine/PCP type drugs, you’re likely to deteriorate big time when placed on a psych drug regimen and then get called treatment resistant, which calls for even heavier doses of psych drugs (which is why I became interested in big doses of glutamine for PCP delirium 40+ years ago).

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        • I watch this happen all the time where I work. Someone is brought in who had problems with the police etc. while they were on drugs. They get sent to us and without any time devoted to actually looking into what is going on with the person they get put on nice, big doses of some neuroleptic, which then causes more problems for them and away we go in the merry-go-round known as the wonderful “mental health system”!

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          • Think of it as job creation, Steve. How many psychiatric area jobs would be lost if these delirious individuals were revived with a few grams of niacin, ascorbate or l-glutamine and were sent on their way when coherent?

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        • Everyone is so vastly different than you, their needs cannot be solved by a single amino acid with a bunch of things like B-vitamins. And then sent on their way totally coherent?

          Some people here are going off on tangents that have absolutely nothing to do with esketamine and how it actually functions in the brain or why it is even being studied in clinical trials and being approved.

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      • It’s not meant to be used as a tranquilizer for horses. It isn’t some animal painkiller alone. It’s been used in hospitals on human beings for quite some time now, everyone. And while some people who have used it recreationally may think it’s awesome and all that, it isn’t bc they are using a horse tranquilizer. Personally, all this talk about something no one here seems to have taken themselves just makes the whole topic just a bunch of opinions and anecdotal observations not even close to being accurate.

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      • Oh please. I was given ketamine in the hospital due to opioids failing to be able to control or handle the insane amount of pain and horror I was in at the time. And yes, I had been given things like fentanyl before, which has had a huge history of being a very helpful substance for people with severe chronic pain issues (or even just post-surgery issues, as I myself have had a script for it before, legally, after botched surgery on my arm to repair a falsely made diagnosis), yet now it is being headlined as this massive killer of people, yet none of this fentanyl is coming from the hospitals. China and Mexico are hugely responsible for manufacturing it cheaply and without enough control that it gets diverted to the streets and misrepresented. But to say that because of this that fentanyl should just disappear is ludicrous! I mean, there goes all the epidurals for women giving birth! Yeah, that’s right, women get fentanyl injected into their epidural location for pain relief giving birth these days. It is a hugely controlled drug (C-II) and way different than esketamine (which is NOT ketamine). That’s just going completely on a tangent. And some people OD on codeine! I cannot even metabolize that stuff! People are so massively different in their medical needs that they assume the horror stories being replayed for attention-getting value are all true and would apply to them, too! You call it a horse tranquilizer yet say no thanks to it if you ever go to the ER or OR? How on earth would you know?

        Ketamine and PCP are not any closer than just being labeled as dissociatives as a drug classification. Well, so is DXM, an OTC cough suppressant. You may as well decline ever using that bc you may accidentally dissociate!

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        • dj

          My injection of fentanyl was given in the hospital after surgery and it almost killed me. It depressed my oxygen level in my blood and started lowering my blood pressure at an alarming rate. A young nurse caught what was happening and called the doctor on call for the hospital. He asked me if I knew what had been given to me and when I said no he said it was fentanyl and that I should never ever take it again as long as I lived. All the nurse told me who originally gave the shot to me was that it was a painkiller.

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    • Daniel, I think your argument makes Esketamine look worse, not better. Of COURSE if you (lightly) anesthetize someone their depression will vanish for a while. Is this what we call progress? If we can’t really help you, we’ll just numb you out? Ah, “modern medicine”….

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    • Anesthetics are used short term for surgeries. Not for a lifetime. Big difference.

      Most people don’t want to sleep their lives away. And most wouldn’t take this crap if they weren’t deceived by drug companies, social workers, and doctors they think they can trust.

      These people will not get accurate information from traditional sources. 🙁

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  7. I applaud all the work you do as a patient advocate Kim. I am so sorry to read about the loss of your beloved husband at Woodymatters. That this tragic outcome was the end result of him experiencing insomnia boggles the mind. Your dedication to his memory and efforts to protect others from harm is very commendable.

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  9. I predict that this is going to be a done deal and that there will be nasal spray galore out there. They’re talking about this on news reports and they’re acting as if it’s some kind of miracle drug. It supposedly takes away the desire that people are experiencing to kill themselves. I guess so, if you’re sedated with something that originally comes from a horse tranquilizer! You’re going to be numbed up really great and won’t be worrying about much of anything. People were breaking into veterinary clinics in New Orleans in the mid to late 70’s to steal the ketamine that the vets used to tranquilize large animals like horses.

    How are they even going to attempt to regulate this???? People get addicted to over the counter nose sprays like Afrin so I’m wondering if this eskatamine is addictive in any way?

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    • Probably this will end up with thousands of people fucked up on ketamine, which might start people thinking twice about psych drugs and related junk science. Anyway, we know what’s likely going to happen so we should be ready to start explaining to people what’s happening to them, and the fraudulent criminal ideology behind it.

      I agree it probably a done deal.

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      • I highly doubt this. This isn’t ketamine. This is esketamine, which has been researched to specifically target suicidal ideation and tendencies.

        If anyone would just read about the mechanisms of action and why the NMDA receptors are now the hot focus of new treatment lines (rather than just serotonin, norepinephrine, and dopamine), it would be an interesting discussion. All these anecdotal references to hearing about it in bars in other people’s conversations or believing that it is just a drug that just fucks people up (as you say) is just Cracker Jack box science, as someone basically has said.

        Can anyone bring any real neurobiology into this discussion rather than just fearmonger a drug that is actually a C-III substance in the USA (it isn’t C-II or C-I) that has been used effectively for many things that aren’t close to what people seem to think it does?

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      • Please do. People need someone they can trust to give them info on what nutrients they may need to tinker with in order to attain optimal health; “an apple a day keeps the fake-ass “doctors” away,” so to speak. I’m sure if I had more information, both general (which minerals can’t absorb together, for instance) and individual to my body, I could do a much better job of improving my quality of life. But please call it something else (though, I gotta confess, I chuckled at the notion of a back-alley psychiatrist, my twisted sense of humor.)

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    • I’m sure the APA is tinkled pink. More folks taking horse tranquilizers=more psychotic breaks. Which means more bogus claims the drug “unmasked” a condition they couldn’t find before. How convenient–for shrinks! Because the drug’s so addictive psych doctors can fool people into thinking they “need” their “medicine” to fix the imbalanced brain chemistry (well informed) shrinks secretly laugh at.

      Just like Anafranil messed my life up. At 45 I feel like a woman of 75.

      When do you think Big Pharma will alter adhesives (slightly) to sell as inhalants for the desperately unhappy?

      I was taught not to abuse mind altering drugs as a kid. The “mental illness” makers told me repeatedly these were different–non addictive brain fixers. Turned me into an unwitting drug addict.

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  10. OK so now the article in Around the Web about the “Prominent Psychiatrist Accused of Sexually Exploiting Patients” says that the guy was prescribing lots of Ketamine for women — does this mean that it’s also an aphrodisiac or date rape drug?

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  13. Ketamine infusion therapy (and ketamine nasal spray) has been in the United States for a while now for treating many things. Ketamine itself has been used in hospitals. I myself have gotten it in a hospital ER setting by anesthesiology. It works amazingly well for extreme pain that is resistant to opioids, and it is amazing for mood and other issues. Having in the hospital was not my first experience with ketamine either. I’ve taken it intranasally before with amazing results. It cured so many issues that I had no idea were such issues to me then. I have seen ketamine do amazing things in other people personally. Otherwise I wouldn’t share my own personal experience with it. It seems pointless to argue about anything’s effectiveness without having personal experience with it, in my opinion. Esp when one dose can last for so long or change a person’s life from dose #1.

    But to state that everyone absolutely will respond the exact same way also is a futile argument. Some people have gene mutations and enzyme variations among so many other physiological differences. Any variation in anything can result in totally different effects and complications. Just like any powerful dissociative analgesic that is also potent on the mind and spirit, it does come with the history of being diverted for nonprescription use by people of stereotyped backgrounds (ie, club kids, college kids, etc) seeking it for recreational use/misuse. This is why anyone who seeks it out should be fully aware of its side effect potential and profile, as there is no one universal panacea for anything.

    Sometimes just seeking help is enough to generate a placebo effect that is enough to promote a person through their obstacle without having to stay on any substance for very long at all. After all, we get what we expect to get out of things, and sometimes we get what we least expect.

    And yes, there are things that are quite scary from an outsider’s perspective, like the prospect of falling into a k-hole. But I do hope that esketamine is not so chemically different than ketamine itself (which is a Controlled Substance in the USA now) that it works along the same routes. Otherwise, comparing the two is really subjective.

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    • My understanding is that esketamine is just one of the steroisomers (two different mirror image molecules) of ketamine, which contains both stereoisomers. What difference that makes is not something that is obvious. It could make a difference in some cases, but I’m guessing (as a chemist) that in most cases, the actions of stereoisomers would be very similar unless they’re engaging some system that only accepts one isomer over the other. And even if only one isomer is active, the ketamine contains both, so if there is a difference, the most likely one is that it would be a more powerful impact of the same effect.

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