The Food and Drug Administration is expected to decide in the coming weeks whether to approve esketamine, which would become the first major depression treatment to hit the market in decades. The psychiatry field is buzzing with excitement — and hesitation.

Esketamine — developed by Johnson & Johnson and delivered as a nasal spray — would be used in combination with oral antidepressants in patients with depression that haven’t responded to other drugs. Many experts have lauded esketamine as an important option for patients in dire need of new treatments — particularly because it could work faster than existing antidepressants.

An independent advisory committee convened by the FDA earlier this month agreed with them. The panel of medical experts voted 14-to-2 that the benefits of esketamine outweigh its risks, which include blood pressure problems, the potential for misuse, and dissociation, a temporary mental state in which a person might become less aware of their surroundings.

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“We’re always weighing the risk balance in treatment. On balance, [esketamine] is definitely of value,” said Dr. Wendy Marsh, a psychiatrist and the medical director of the Depression Specialty Clinic at UMass Memorial Medical Center.

But some experts aren’t convinced that there’s enough data just yet to show that esketamine is effective. And they say they want more details on how the drug should be used in the long run.

“There’s sort of a split in academia. Some are cheering for something new and others are more skeptical,” said Dr. Erick Turner, a psychiatrist at Oregon Health and Science University who serves on the FDA advisory committee that recently evaluated the drug. (Turner didn’t take part in the panel earlier this month for travel reasons.)

Johnson & Johnson submitted five Phase 3 studies on the drug: three-short term studies, one maintenance study, and a long-term safety study. Two of those turned up positive results. One was a randomized trial in adults under age 65 with treatment-resistant depression who were started on an oral antidepressant and intranasal esketamine. After a month, roughly 70 percent of patients who received the treatment responded compared to just over half in a placebo group. The researchers considered an improvement of 50 percent or more on a common depression rating scale as a successful response.

The other positive study was a maintenance-of-effect study, in which participants who responded to esketamine in one of the short-term studies were randomly assigned to either keep taking it or be switched to a placebo. The FDA generally wants to see two successful studies for approval — but historically, withdrawal studies haven’t counted toward that total.

“The threshold has been two adequate and well-controlled trials. In this case, they only got one,” said Turner. “Based on that, I would have voted no,” he added.

A spokesperson for Janssen — the subsidiary of Johnson & Johnson that developed the drug — pointed to the positive results that showed esketamine could have a significant effect on treatment-resistant depression in some patients.

“Janssen has a strong track record of bringing important medicines with novel delivery models to market that have helped to address critical healthcare needs of people around the world,” spokesperson Greg Panico said.

Julie Zito, a professor of pharmacy and psychiatry at the University of Maryland, was one of just two advisory committee members who voted “no” on the question of whether esketamine’s benefits outweighed its risks. She said that if the drug is approved, she would want to see providers, patients, and the families of patients work together to keep tabs on possible side effects and how well the drug is working.

“I have no doubt in my mind that this is a very useful treatment,” said Dr. Gerard Sanacora, a psychiatrist and the director of the Yale Depression Research Program, but that “has to be balanced with how do we use this rationally and in what step in care do we use this medicine.” Sanacora has been involved in several of the esketamine trials and has also served as a consultant to Janssen.

“This is gonna be the big question: How do we use this in the clinic?” Sanacora said. Janssen has said that esketamine would be given twice a week during the first month of treatment, then reduced to once a week or once every other week during the maintenance phase. But psychiatrists say they still have questions about long-term treatment with esketamine, including how long to keep a patient on the medication and what the risks of long-term use might be.

“I certainly would love to see ongoing studies for treatment duration and frequency,” said Marsh.

Another big concern among experts: the hype around esketamine. The drug is the chemical mirror of ketamine, a longtime anesthetic that can be abused recreationally at higher doses. In recent years, as early studies pointed to the drug’s possible antidepressant effects, there’s been a boom in the off-label use of ketamine as a treatment for depression and other mental health conditions. Dozens of clinics have opened around the country to treat patients with ketamine, which, unlike esketamine, must be administered intravenously. Patients are paying $350 to nearly $1,000 per infusion, and many get six rounds of treatment, or more.

“There’s been a lot of hype about ketamine in general. … There’s this belief out there that it’s this kind of miracle drug,” Turner said.Turner said that while there’s evidence that esketamine works, he’s worried it’ll be seen as superior to other drugs for treatment-resistant depression or as a therapy that can produce very rapid effects — two points he says studies don’t yet support. That type of hype, he said, can mean patients get their hopes up about the drug “to a degree that’s unwarranted.”

In Sanacora’s role as a researcher, he has often heard from patients who want to know why they can’t just try the drug before first seeing whether they respond to standard oral antidepressants. He’s concerned that the excitement over esketamine might lead patients to look to it as a first-line treatment before trying other antidepressants — or even as a cure.

“The danger is having it so positively portrayed,” Sanacora said. “I’ve been around enough to know this is not necessarily a condition that responds to miracle drugs.”

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  • As a bipolar II patient with mostly depressive episodes, and a lengthy laundry list of failed RX treatments behind and 100s of hours in therapy, I can tell you, I was extremely skeptical when a Ketamine compounded Rx was suggested to me by my Psychiatrist. However, coming off of an extreme lithium toxicity reaction in the last several weeks, (at only 300mg BID, loading dosage) and having gone to THAT mess because of a new Dx of NASH/Cirrohsis, I am out of options. That all said, I was skeptical but have had to place all of my eggs in one basket. I picked up my Rx today, 4/1/19 and have been utterly amazed in what it’s done with only 2 doses. My thoughts quit racing, I have been able to concentrate, my shoulders have eased down into an almost normal position on my frame, (normally kept near my ears from anxiety and pain.) I have had zero panic attacks since my first dose at 6PM this afternoon. My mood is lighter, I’m not jovial or effervescent like I used to be before being diagnosed with my psychiatric problems, but I actually am sitting here, responding to this post, and thinking that I can breathe in and out and the world won’t crash around me, or that I won’t want to die already from my health issues. I have a long way to go, and this is only on 2 initial doses (1 squirt both nostrils every 6 hours, Ketamine 25MG/ML.) I actually don’t know if it would be better to have this approved or kept off the market and compounded. My 30 day supply was only $35.00 cash price. I know that it will skyrocket if it’s approved. I also know that my Medicare/Medicaid Rx plan most definitely won’t cover this if it’s put into production. And then I will be facing ECT and I honestly would rather die than go through ECT if it’s half as debilitating as what I’ve been through for the last 3 weeks dealing with the Lithium toxicity.

    If you are afraid to try this, because it’s a novel treatment, don’t be! The only side effects I’ve had, with each dosage, have been a cold/scratchy feeling in the back of my throat and nose immediately after use, lasting about 30 seconds total. And a few jaw cracking (in a wonderfully relaxed sort of way) yawns. That’s it. I feel better tonight than I have in 5 years.
    I will update if anything new crops up, but so far, I’m pleased. Extremely so!

    • are you saying you were prescribed the esketamine, picked it up at a compound pharmacy and used at home?

    • Sean, no, I was given an Rx that was compounded for me at a local pharmacy that handles that type of order. I was not aware that esketamine was approved yet in the US. I was bemoaning the issue that if it does become approved here, that the price will probably sky rocket once Big Pharma get their greedy claws on it. I know that it will be practically impossible to convince my Rx plan insurer to cover it. I don’t know if I will be able to still have my Rx created locally once the Esketamine is in production or not.

    • What pharmacy for you use that compounds it? Can you give me more info on strengh and everything, so I can ask my doctor about it. Thank you so much!! – Shanee
      P.S. I’m treatment resistant, why were you put on it??

    • For Shanee,

      I am in the U.S. The only compounding pharmacy close to me is The Medicine Shop (or maybe Shoppe?) I know it’s a chain of pharmacies in Ohio and West Virginia. I am near Huntington, WV. The strength is 25mg/ml and the dosage is 1 squirt to each nostril 4 times per day. And the cost for the medication is $35.00 cash price.

      I have been diagnosed with Cirrhosis of the liver, and ketamine is an excellent option for me as it’s not processed through the liver (like almost every decent anti-depressant on the market, unfortunately.) I, too, am fairly treatment resistant and the list of pre-Cirrhosis Dx medications I’ve been tried on is well over 35 different drugs and/or combinations of drugs. Nothing has helped me the way that this nasal spray has helped me. N.O.T.H.I.N.G. It has literally been a lifesaver.

      After nearly 2 months of use, the only significant side effects I’ve had have been an ice-cream headache from the instant I first squirt the medication, and it lasts about 15 to 20 seconds tops. Also, there is a sort of ‘cold’ sensation at the back of my throat that lasts about the same duration of time. The other side effect, if you want to call it that, is a horrible bitter taste, which I combat with a couple of sips of orange juice.

      One other note and this is not a real problem unless I forget more than 2 doses of medication in a row, is that I do get CRANKY by the time for that 3rd dose. But that is my normal MO anyway, I have been a hyper-irritable person for so long, I thought that was just who I was now, I forgot that I’m actually pretty pleasant and easy going. (haven’t seen that person in so long I thought she was ancient history.)

      I really like the option of being able to control the drugs use myself, from home, and not having to go through the plethora of hoops necessary for the FDA approved medication (purchasing your Rx, taking it to your Dr. to store, going to their office to use the product on yourself, waiting 2 plus hours post use before being released, and then ALSO having to have a driver take you home. Too many hoops!)

  • Esketamine is a fast acting powerful stimulant that creates an instant “high” sensation. Esketamine is being used more and more in illegal recreational use because of the instant “altered state effect” it creates.

    In clinical trials, six patients who were taking the drug died, three from suicide. Esketamine creates a feeling of being temporarily “disconnected” from your body and your mind.

    Conclusions from tests are misleading. Esketamine is a stimulant that alters perception. In the immediate short term patients perceive improvement in mood but as soon as the stimulus wears off so too does any perceived benefits and the crash from the “high” altered-state increases depression.

    Johnson & Johnson are currently working in overdrive hyping this product for obvious reasons, profit.

    Esketamine is a stimulant and not a miracle drug.

  • As a participant in the esketamine clinical trial, I experienced dramatic improvement from a weaker formulation than IV ketamine, with non-invasive dosing and zero intense disassociative effects. As far as I’m concerned, intranasal esketamine is a miracle drug. I sincerely hope that it is approved. The greedy Drs running needle mills that offer insanely priced ketamine infusions are predators who profit from the misery of others. They are a disgrace to their professions.

  • This drug wouldn’t need to be developed or sold at what will likely be exhorbitant prices, if insurance would cover IV ketamine treatment for depression. Ketamine is a generic that has safely been used for decades even in pediatric patients. There have been positive results published for quite some time now. I’ve personally been treated with great results for 2 years until I could no longer afford it. Our health system is shameful, and I work in it!

    RN and depression sufferer

    • Lisa,
      I too suffer from treatment resistant depression and would love to chat with you. Our healthcare system is awful. Our mental health care is worse yet, especially in Iowa. If this works…I will advocate to the highest for it’s availability and cost

    • Hi Lisa, (and Janet, and others)

      It’s perhaps not the same thing, but I have narcolepsy- I know, I know, I can’t believe it either and it’s both a relief to know and terrifically embarrassing- it’s very clear to me that our healthcare system condoned an extremely overt attempt at social engineering in it’s acceptance of the premise that,

      “psychotropic effects, if they are perceived as positive, are bad for a person’s mental, as well as physical well being and inasmuch as they modify the perception of social and environmental pressure they cause social harm- these pressures ought to, or even must be felt in their full gravity for the individual and the society to function.”

      …as if the Vikings couldn’t maintain villages, or the Mongol Horde needed to supervised to operate as a team while working, and in the self-written history of Mediterranean Europe modernity was founded by a savage killer who was raised by wolves and raped the Sabine women, if there were any vice police in Rome then I would be shocked- they did use intoxicating medicines- the people who invented the aqueduct and ate off of disposable, north African dishware at restaurants in Britain- they didn’t even consider the unregulated distribution of intoxicants threatening to their institution of slavery.

      YES, that’s melodrama, I know, it’s melodrama- it’s still worth mentioning inasmuch we are now fairly well aware that the mind and the body work pretty closely together, that the mind does not, “feel good when it sins, which causes disease,” and I’m very well concerned how much like, “what vices caused this illness, and what virtues will cure it,” our belief in drug addictions must be described….

      …and at the same time?

      I read on the front page of the Wall-Street journal while waiting in line the other day that research into an alzheimers medicine came up empty- is it just me or did they probably not try anything on this list: deadiversion.usdoj.gov/schedules/

      Which frustrates me because half an inch deep into it’s own logic it makes not sense, a 75 percent dextroamphetamine and 25 percent levoamphetamine mixture that is called adderall is considered super safe for children but a 50/50 mixture I like a lot better quite specifically because it’s less intoxicating, in the traditional sense, is considered, “very highly likely to be abused,” and all of this nonsense like it’s radioactive- my doctor is a good doctor, so I have it anyway, I just hope I never have to defend her against the DEA in court- my point is that at some point it’s like, “bro, have you tried it- seriously, with less than a ten foot pole, do you have any idea what this stuff does?”

      When I was a teenager, on a school trip to London, my friends Joey and Allison and I bought a case of a Schmirnoff Ice Knockoff called Red Square and drank it until we puked while smoking Marlboro- Amphetamine is Nothing Compared to Red Square, and, anybody who can’t handle Red Square shouldn’t be a Doctor- imho, and it’s only that, but I have actually tried both, and adderall, and unlike the U.S. Government I don’t have a taxonomy of Sin penned out and since I’m neither the most responsible, nor least- just normal- it doesn’t seem fair to me that I’m entrusted with a Serious Dope that almost everyone else in this country would get locked in the slammer for….

      …and no one would ask, “why you wanna be so awake for, anyway?”

      You know what I think?

      I think everybody’s circadian rhythms are all guttered to hell, I think that they can’t sleep, or relax, that liquor smells like liquor and makes you wobbly and they don’t have enough of a social life to go to parties that might excuse that so they’re doing dope to squeeze joy out of the pavement and keep a smile on for the, “no fun life,” and that we should have guessed these drugs could help people when Black Dudes in the G-D Prewar South could do day jobs with a side hustle of “Jazz Musician,” right?

      I’m fairly sure the Mormons are the Firstish Distinct Culture to Always Be Sober, and that’s weird- that isn’t ideal, it is ideal for a bank trying to predict your behavior or a company that wants your labor as predictably as if anybody working their cared about you…but, in this case you’re disposable…and it’s pretty much just facelessly large companies wherein that’s the case.

      I work in advertising- and don’t really drink much, it’s probably been a year since I’ve been drunk- but I could do this fucking wasted, and if called wasted what it was- seems to be for a lot of addicted people, it would be something like,

      “An aberrant state of mind, judgement or mood in response to an exogenous agonist, antagonist or absence of an analogue to a neurochemical,” which is to say that it is our language that says that opiate addicts are, “high,” when they feel, “par with everyone else and capable of fulfilling their expectations on a normal day,” but, “sober,” when they are very, very ill and depressed due to an effect which could be replicated by a, “drug,” that you or I could take right this minute.

      Similarly- although I am fulfilling an extremely tragic stereotype by writing such a long message; I write for a living, I respect my voice, and I have something to say- it’s when I’m, what, “spun,” that I’m actually capable of being an equal in terms of some very basic appearances of effort- and yet it’s what I do, take medicine with some pretty heavy effects so that I can be a normal person and contribute….

      My being useful and helping the couple people I love is the most important thing in the world to me- it is most people, I think, and anyway I would really like to talk with you and Janet and anybody else who is interested about our healthcare system, this treatment, these sorts of things.

      I live in Saint Louis City; this is kinda a place where if I make a super good argument, things might actually change, and I’m like….

      I have lost a very, very large number of people to depression and opiates combined- if our government thought back in the 1930’s it could cull the shoreline of it’s weirdos by checking who had to be on dope to look normal?

      Makes sense to me- these same police structures are shit at doing what they were alleged to also and primarily do, and I swear to god- the dead people, I have so many dead people, I lost six in the latter half of last year- it’s frightening to consider that someone might think,

      “this will be good for another 150 years,” it won’t, and I won’t be shocked if the things we feel in our noggin do other stuff too- that it might be that instinct to avoid boredom, with intoxicants, that keeps us safe from neuro-plaque, even, why wouldn’t it be?

      We’re not necessarily born to contemplate the Jesus all the time, are we?

      (sorry for the length, just wanted to say my peace on it)

      Jonathan

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