I wonder if J&J got a patent on S-ketamine? The patent system is often abused this way. First you sell the racemic mixture, then when that patent is about to expire, you start selling a new product that is just the active enantiomer. And you can tell customers that it's new and improved: that you only need to take half as much! See Prilosec/Nexium, Celexa/Lexapro, etc.
Although, maybe it's difficult to manufacture just the one enantiomer, at scale?
Also the racemic intranasal ketamine was already patented:
(Incidentally, we have some evidence that the metabolite that causes the effect can be blocked via concurrent CBD administration - without reducing the dissociative effect)
The standing appointment to get slightly high for a couple of hours every three days does get inconvenient (though it's not as problematic as the resultant insomnia). I expect esketamine will be more so, for less antidepressant effect. And, being a controlled substance, I'm concerned I'll be unable to increase my dosage to make up the difference.
 - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4065787/
 - https://www.ncbi.nlm.nih.gov/pubmed/29501990
I suppose it didn't occur to him that the company trying to get their drug approved might not have taken the patient voice into account enough either? Or maybe under-reported certain patient voices? (The adverse ones. Hey, it's not like it has never happened. At least take a closer look!)
Evidence and studies like this should not be done by the company itself. The OxyContin claims about low addictiveness should be a timely reminder for independent clinical studies. Reading that set off alarm bells for me.
Opiates, for example, do solve certain problems very effectively. That doesn't mean they're not extremely abusable and dangerous to use without proper caution.
Frankly, it's also going to be hard to distinguish between some types of addictive behaviors and people desperately seeking to avoid sinking back into the morass of their mental states prior to effective treatment.
SSRIs are useful meds, but they're not miracles.
Sometimes I hear people mention that ketamine’s special effectiveness (in those whom it is effective, which isn’t 100% of people afaik) wears off over the length of a treatment protocol. It’d be nice to hear more about that, especially in comparison to the long-term effectiveness of traditional antidepressants and SSRIs in particular.
I'm eager to see it come to market, and for it to work, but I'm scared to work with my doctor to try it based on those stories.
To put it mildly, not the most pleasant experience of my life, but still looking forward to seeing where the next iterations on rapid-acting antidepressants go, and whether they turn out to be any more durable.
(Also quite curious to see what research crops up about why the effects are sometimes not durable, but that's gonna be a decent wait.)
If the answer is "no, but the marginal differences between ordinary ketamine and the new drug are enough that you'd want to prescribe the new drug instead"--well, that's new value added, isn't it?
The IV protocols for non-life-threatening cases usually involve a number of treatments over a short period (say 6 over 2 weeks), then increased spacing until a satisfactory equilibrium between avoiding symptom recurrence and not spending too often strapped to an IV is achieved.
I believe the nasal spray treatments are more frequent and less potent, but I've no firsthand experience with those, just the knowledge that one of the major limiters on getting a ketamine derivative into people's hands outside of an IV bag is the variability of dosage through e.g. nasal spray. (You can get a prescription for ketamine in a nasal spray from compounding pharmacies right now, but you will likely have decent variability of dosage each time.)
FDA will approve drugs from companies or individuals that pay for the application. The cost is pretty high today, something on the order of $2-3M USD just for the application. That's not including the cost of supporting data you need to have (Phase 1-3) that will likely cost a large amount to support (multiple centers, paying participants, wholesale cost of drug, paying investigators, researchers, statisticians, etc). Side note, should companies be able to justify exorbitant prices for their drugs based on this cost? No, probably not, but smarter people than myself have debated this on HN.
Why do I mention this? Because ketamine for use in intranasal form for treatment of depression is not off patent. That's right, Mount Sinai Hospital (Icahn School of Medicine) was granted that patent in 2007. A non-profit institution, mind you. So, if I were a drug company, looking to make a profitable form of intranasal ketamine, wouldn't I try and sidestep the patent entirely, reducing overhead on my end?
Also, calling esketamine a knock off is disingenuous. It's an enantiomer, therefore literally half of what is in normal ketamine. It's also probably the more potent half.
Edit: originally wrote that ketamine patent was granted in 2017, meant 2007.
Edit2: originally wrote that NYU held the patent to intranasal ketamine when it was actually Mount sinai hospital.
The risk of abuse and addiction from using ketamine in a surgical setting is incredibly low. That's not necessarily the case (in fact, it definitely isn't) for nasal spray given as a treatment for depression.
Same drug, but completely different use case. It's very well known that it's a physically safe drug, but there is a definite risk of abuse and addiction, as evidenced by the number of people I know with ketamine abuse problems. It's not a drug that should just be given out willy nilly to everyone with depression, in fact a lot of people I know who have problems with ketamine abuse are clinically depressed or have other mental health issues.
People who want recreational drugs will find them anyway. Letting innocent people die from treatment-resistant depression is a perverse priority.
"The voice of the pain patient is underrepresented! We should approve opioids"
"The voice of the depressed patient is underrepresented! We should approve nasal ketamine".
I'm all for new therapies but ketamine can be highly addictive and causes really nasty side effects in high quantities (bladder problems being horrific from what I've heard). I hope we don't see a huge spike in ketamine abuse in 10 years time like what happened after overprescription of opioids.
I also think this will be extremely popular. Current antidepressants are not very effective and take a long time to work. This seems to work very quickly. Who would want to wait 8 weeks Vs hours to get better? It would not surprise me if J&J have massively downplayed the potential addiction risk of this.
Subjectively, it’s not as good a “take the pill and forget your problems” drug as opioids, benzos, and alcohol are. It can be used in that way if you take a huge “k-hole” dose and dissociate completely, and some people do get addicted. But at common doses, certainly whatever they are going to prescribe, it’s more of a “think about your problems and figure out how to solve or accept them” drug like mushrooms and LSD.
Exactly the same thing could be said about opiates.
I'm all for new and novel methods for treating depression, but everyone seems to be jumping on this like it's a magical depression cure with no negative externalities.
I'm not saying it is addictive as heroin etc but it's definitely addictive. And will people start increasing their doses as they become tolerant to the antidepressant effects, etc?
Group A: Drugs like benzos, alcohol, and opioids provide pleasant sensations upfront, killing your pains and anxieties, but those problems return in even worse form when the drug wears off. It’s as though your brain’s baseline for what counts as suffering had been lowered by the experience of being coddled. It’s very clear how this leads to compulsive redosing and addiction.
Group B: Psychedelic drugs like mushrooms and LSD induce unpleasant feelings as they take effect, followed by a more positive (perhaps euphoric) experience once the brain adjusts to the presence of the drug, and then less potent pleasant after-effects when the drug wears off. It seems like the brain has raised the bar for suffering - suddenly the fact that you can see things in the correct color, gravity is pointing in the right direction, and you have clarity of thought makes life feel easy. You might redose to extend the peak effects, but you aren’t going to take any more for a while once it wears off. It would be tough to get addicted to these. However, a depressed person might have trouble with the come-up, and could experience a panic attack. You’d want a very skilled therapist if you’re trying to treat depression this way.
IMO ketamine kind of straddles the line here. The onset of the dissociation can be stressful, but it’s not that hard. You don’t forget your problems, but they feel like the problems of somebody that you know closely and care a lot about, so you can try to solve them from a different perspective. You can feel that you are doing something great, which can lead to compulsive redosing, but you keep the lessons you learn when it wears off. It’s not as though your problems come back in even worse form like you get with group A. Although if you really blast yourself, the dissociation can get so strong that you don’t care about your problems at all, which gives you more of a group A experience while you are peaking. I’m not a scientist and I may be wrong about this, but I think the antidepressant effects are not caused directly by the drug or metabolites that one could become tolerant of. I think that they are a result of the brain’s recent experience of looking at life from a non-depressed perspective.
It's that millions of people will be taking it when they never would have before from a doctor, and it is definitely addictive. Drug companies have an insane incentive to down play/hide studies that show it is addictive.
Emotional language like "letting innocent people die" is a huge red flag when it comes to having a good discussion about the issue.
Ecstasy is a stimulant, not a hallucinogen. I thought bloomberg was generally considered to be better at fact checking than that.
Or expand the name, and recognise it as MDMethamphetamine.
Ecstasy/MDMA. MDMA (3-4 methylenedioxymethamphetamine) is a synthetic, psychoactive drug chemically similar to the stimulant methamphetamine and the hallucinogen mescaline.
I thought bloomberg was generally considered to be better at fact checking than that.
They are. You’re not.
The use and abuse of MDMA (3,4-methylenedioxymethamphetamine, or ecstasy) is a significant public health concern. In the United States, MDMA is classified as a hallucinogen, a category comprising LSD (lysergic acid diethylamide), PCP (phencyclidine, or angel dust), peyote, mescaline, and psilocybin (mushrooms).
That was a huge blow to my ability to trust Bloomberg's journalistic credibility, along with several others' trust I'm sure.
Granted that was clearly a different reporter and a different field altogether, but the name "Bloomberg" alone should no longer lend the same credence in this era of fake news.
Food for thought.
The primary effect of LSD isn't hallucination, but something far more strange and more difficult to describe.
MDMA is both a stimulant and a hallucinogen. In smaller doses the effect isn't noticeable, but it's definitely there in larger doses.
There is very little evidence that depression is caused by chemical imbalance in the brain, it's something that big pharma have sold you so they can sell their drugs.
Great book on the topic, check out lost connections.
The problem with SSRI's, especially in my experience and from my understanding, is that they aim for "mildly beneficial with minimal side effects" and hit somewhere closer to, "mildly beneficial with understated side effects that many patients will be too embarrassed to report". This doesn't mean SSRI's are total junk, but it does mean that they're kind of mediocre.
Ketamine is more of a high-risk high-reward drug, similar to the use of CNS stimulants to treat ADD. There's no question that amphetamines help people focus. There's also, understandably, far more concern about giving people amphetamines in the first place.
Also, it's easier to convince patients to take a boring prescription drug than to sell them on, "I think the real solution to your problem is this really scary-sounding drug that people take at raves; trust me, I'm a psychiatrist."
A broken bone can be fixed by immobilizing it via a plaster cast. Did the bone break due to the lack of plaster?
Eczema can be fixed by applying topical steroids. Did eczema develop due to the lack of topical steroids?
Depression can be fixed by inducing changes in neurochemistry. Did depression arise due to an imbalance in neurochemistry?
> The results are reported after 8 weeks of treatment, so we don't know if they apply to long-term use of antidepressants.
I'm not sure why you would discount an improvement in symptoms over 8 weeks though. Many major depressive episodes will be resolved in that time ("The median duration of MDE was 3.0 months; 50% of participants recovered within 3 months"), so even if they are not suitable, or less effective, for long term care, that can still be a improvement in quality of life.
(FWIW, it was 21 antidepressants, not 21 studies: "The researchers found 522 studies covering 116,477 patients in total. This included 101 previously unpublished studies.")
I'm not, but I don't think anyone is arguing that SSRIs can't be effective for some people with severe depression when used in the short term. The issue is that that only represents a small percentage of patients.
He found they didn't work better than Placebo.
I looked up the first thing I found on Google.
This is written about Kirsh's study, and it's confusing. Kirsh interpolation of the raw data showed that antidepressants don't work, and work less so for extremely depressed patients.
This doctor claims the opposite?
Pesonally, I find the research on the efficacy of antidepressants very confusing.
To those whom are depressed, I can offer this, it does get better with age.