Ketamine for the acute treatment of severe suicidal ideation
bmj.com
bmj.com
This really shouldn’t be labeled as double blind.
1.The nurse administering knew if it was placebo or active (for safety reasons).
2. It would immediately become obvious to the subject if they were injected with salt water or ketamine.
3. Within minutes it would become obvious to everyone in the room if the patient was injected with salt water or ketamine.
Some trails are impossible to be double blind. That’s okay, there are other ways to address concerns of internal validity. Pretending like this trail is double blind does not address any internal validity concerns, and only raises concerns about the researchers understanding of experimental design.
But I suspect that would take many years to get through the permitting apparatus, if it was at all possible.
The classic gold standard is to randomly assign subjects to groups. Then give one group a sugar pill, give the other group the treatment pill. Neither to patient, the person administering, or the person recording the results know who got the treatment who got the placebo. This is not possible with ketamine, psilocybin, MDMA, LSD, etc. That's fine, we can still build a strong body of experimental evidence of their efficacy. It bothers me when clearly non-blind non-mask experiments are labeled as double-blinded, which we see often in this body of research, this study included.
I'm not saying it's impossible to conduct good experiments on these substances. I'm saying that they require special considerations of internal validity and it's incorrect to call this study (iv ketamine vs iv saline water) double blind.
[Edited to clarify.]
It's common for those wordings to be used because often it literally is a handing over of drugs you're talking about - with sickness you're more likely to talk about the moment a medical person said to start using a drug than to tell people about the actual use because it's usually more interesting.
At 0.5mg/kg intravenous, there's no way that people wouldn't feel anything. It's not necessarily a "drug trip", but pretty much anybody can tell the difference between that large of a dose of ketamine vs. a saline solution.
For trials in cases like this, it's common to use a group which receives either a smaller dose of the drug or a drug that is intended to mimic some of the subjectively observable side effects.
I do not know what a trip is or is not supposed to be like but it was a very wild sensation.
The problem with ketamine and suicidality studies is that suicides - thankfully don’t happen very often - so we have no direct evidence that ketamine prevents suicides. Of course if it would only alleviate suffering and wouldn’t increase the rate of suicides, that would be a win too.
0.5 mg/kg intravenous. For frame of reference, a small recreational dose is between 5-25 mg (insufflated[0]), and a larger recreational dose (for people targeting a "k-hole") is more like 50-100mg. For clinical depression (ie, not this study, but for a similar purpose), the fixed dose is 84mg (not weight-based).
So assuming a 75kg individual, that would be a 37.5mg intravenous dose, which is definitely going to provide a noticeable effect for any ketamine-naive user (ie, someone who does not already have a tolerance for the drug from recent prior use).
> The problem with ketamine and suicidality studies is that suicides - thankfully don’t happen very often - so we have no direct evidence that ketamine prevents suicides.
That's not really a problem - suicidal ideation is a strong enough predictor for suicidality and mental health that it's common to use as a biomarker. In other words, nearly anything that reduces suicidal ideation is presumed to reduce suicidality (on a large scale) - it's not necessary to wait months or years to see what happens (and in fact, depending on the specifics of the study, it can be considered unethical to do so).
Source: former clinical researcher and drug counselor
[0] bioavailability when insufflated is significantly less than other means of ingestion
About the first point, I still disagree with the parent comment. The standard 0,5mg/kg ketamine is given under 40 minutes. I've seen two patients receive it. The room was dimly lit, silent and peaceful, as to not induce or exacerbate any possible dissociative or hallucinative side effects. The patients didn't report any side effects at first and later reported a little sedation. I wouldn't be a able to tell with certainty if they had received a placebo or ketamine, and certainly not within minutes.
Source: psychiatrist in training
Edit: I still think we need hard data about anti-suicide effect and not just surrogate markers. Variability in suicidal ideation is suggested to be a predictor of suicide attempts [1]. If ketamine first gets someone better and later on they relapse, they could, in theory, be at increased risk for suicide. More long term data is also needed about it's long term effects. Note that I do think it's a good thing that ketamine is becoming more available! I will continue to suggest it for e.g. patients with treatment resistant and severe depression.
[1] https://www.sciencedirect.com/science/article/abs/pii/S01650...
.5 mg/kg
I was numb all over, my lips tongue and throat were numb.
I melted in to the chair and felt like I was up down and sideways at the same time.
You would not be able to tell immediately but I put on my blindfold within 7 minutes due to effects starting.
And I'm not drug naive by a very long shot. On my 2nd infusion there was an older gentleman across the hall from me who had never had anything stronger than scotch whiskey. He was not having a good time at all.
7 days falling in and out of the K-hole while hallucinating is not as much fun as it sounds.
A friend of mine did it last week and he described it as the most intense experience of his life. He’s 40 and he has experience with other drugs.
I think possibly you don’t know what you’re talking about?
It was more intense and less intense at the same time because I did not know what to expect.
At home treatments with sublingual trockies have much less side affects, but differently still noticeable. Nasal spray is the weakest with just some minor body numbing.
A lot of people take amphetamines as a medically prescribed treatment for ADHD (and other conditions such as narcolepsy too). A lot of people take amphetamines recreationally. Studies done on the negative heath consequences for recreational users are largely irrelevant to medically prescribed users, because your average recreational dose is an order of magnitude (or more) higher than the average prescribed dose. Increase the dose ten-told, it acts like a different drug altogether.
Plus, the irregular dosing schedule of recreational users probably isn’t helping either. And many recreational users try to get the drug into their bloodstream as fast as possible (injection, snorting, smoking), while most prescription drugs aim to be released more gradually (oral route, sometimes even extended release or an inactive prodrug such as Vyvanse/lisdexamfetamine)
What you're saying applies in other cases, but in the case of ketamine, the recreational dose is one or two orders of magnitude lower than the clinical dose.
How numb does it make you. My mouth and throat being numb was very surprising.
You certainly notice the effects of IV K. So do other people when you start to talk to a hairbrush. It's a bit draining after a few days though, and not terribly fun.
However, I have no idea how other sedations feel, so who knows if they are a good placebo. Could be.
I read it as the nurse preparing the IV's knew if it was a placebo, it doesn't really say that the same nurse administered the IV's.
Can't you achieve all of those by having someone else create the bag and then label it for the patient. The "right medication" is the one they're receiving as part of the study.
It's not like what they need to do is different if it's ketamine or saline.
For that matter, a quick web search shows that at least some of the (injected) coronavirus vaccine trials were double blind. Seems like enough for someone in the next room to know if the maybe-ketamine injection is placebo, so they can unblind immediately in case of a bad reaction.
For orally dosed RCTs, often the pill making process is the way the blinding is done -- i.e. they're either in brightly-coloured gelcaps or a film or sugar coating. If it is a double-blind RCT it must be double blind. All of this will have been explicitly examined in the ethics statement for a trial and very, very prescriptively laid out.
> 3. Within minutes it would become obvious to everyone in the room if the patient was injected with salt water or ketamine.
I think you’re mistaking IV infusion for injection. The dose is given slowly over 40 minutes, not as a rapid injection. The patient would barely have any of the drug in their system in the first few minutes. Given the short duration of action, it wouldn’t produce peak levels anywhere near what recreational users experience.
In the sessions I had with IV ketamine, it is very, very noticeable and fairly trippy. The eye mask and the music certainly help, but the ketamine is inducing some crazy sensations.
I don’t remember the exact dosages I received, but I remember it being in line with what I saw others reporting online from their experiences at a clinic.
this is not part of the definition of double blind. There maybe drug effects and there may be placebo effects. If you don't know and the person administering it doesn't know, then the effects you report or measure are what is being studied over the group of people in the study.
> 3. Within minutes it would become obvious to everyone in the room if the patient was injected with salt water or ketamine.
also not part of the definition of double blind.
I'm saying this as a huge fan of the positive impact of ketamine.
There are some symptoms that seem like they need more rewiring.
I’ve done 20 ketamine sessions over the past 2 years (the last one about 5 months ago). I agree with you that a lot of the immediate relief from an infusion can fade after not that long. However, combined with some of the other work I was doing there was a slow accumulation of benefits and new perspectives on life.
Overall, the infusions definitely helped… it hasn’t been easy going though, and I have been continuing to work on myself.
A few months ago, I finally found a therapist who I felt was actually helping me. I had tried a few different therapists in years past and it wasn’t that helpful. My current therapist uses a lot of “somatic therapy” in her work, which I think is really important. With trauma, talk alone won’t get you very far.
I’ve made a lot of progress since November when I started seeing her. I think the Ketamine and the work I had been doing on my on own “prepped” me in a certain sense.
Your friend might benefit from finding a good somatic therapist.
I did 2 surveys and a phone consult then a baseline depression survey before my first infusion.
I go to the clinic and go in my room and they give me my IV then the doctor hangs the ketamine mix bag, hooks it up and leaves. The rooms are dark and they have colored lights or a dim light. I wear an eye mask.
I pay extra to receive talk therapy during the infusion so I have a therapist with me the whole time. We do a ceremony to start each infusion and set the intent just before the effects start.
They have a head doctor and then an anesthesiologist that handles the actual infusion.
what about side effects also ?
colorful emotions: Yes. I've gone inside a rainbow and swam in a lake of my own feelings
The biggest thing you do is disconnect from your self. I've become the particles I'm made of and often lose the sense of what it is to be human or if I am human or not.
"At week 6, remission in the ketamine arm remained high, although non-significantly versus placebo (69.5% v 56.3%; odds ratio 0.8 (95% confidence interval 0.3 to 2.5), P=0.7)."
1. The "placebo" received standard treatment for suicidal ideation.
2. We should expect a natural regression towards the mean. The vast majority of humans do not experience suicidal ideation in a particular day. People with suicidal ideation tend to move towards the standard human experience of not having suicidal ideation over time.
While it probably works for some people, it's likely dangerous for many others.
Kenji Hashimoto and others have published numerous papers about this. It's not exactly under-researched. The incentives in the US are horribly misaligned.
Quite honestly it's upsetting that spravato even exists and there ought to be a huge class action lawsuit about this.
A few papers: https://pubmed.ncbi.nlm.nih.gov/32224141/ https://pubmed.ncbi.nlm.nih.gov/26327690/
https://www.nih.gov/news-events/nih-research-matters/how-ket...
Question: does reducing suicidal ideation reduce suicide? I mean, it sounds like it obviously should, but we've been wrong about this before. Many heart medications to reduce cholesterol worked great at reducing cholesterol without reducing heart disease!
All that said, reducing suicidal ideation is a worthy goal itself, even if it doesn't reduce suicide. I'm a full supporter of seeing this treatment move more mainstream.
I just started IV ketamine infusions at .5 mg/kg for depressions.
I am not finished with my treatment yet.
Ask me anything if you would like.
> Any issues with your bladder? Have doctors mentioned anything about the potential damage to the urinary system? This seems to be the scariest side effect.
We're lucky because ketamine has been used for decades in inpatient settings at much, much higher doses than what is being used now for psychiatric purposes, so we have a good sense of its safety profile already.
Urinary tract and bladder issues are noted for long-term and frequent recreational users of ketamine, but not really for anesthetic use. The dosing schedule for psychiatric use is closer to anesthetic use than it is for recreational use.
The effects also are reversible if detected early and use is ceased, so periodic but infrequent treatment is unlikely to result in long-term damage, both because it's not frequent enough to accumulate, and because you can stop if it becomes a problem.
I am a man and it did immediately reduce my libido. Not in the same way SSRIs did. Will be curious to see if that is a lasting effect or not.
I was only nauseous for maybe 1 minute but I can see it being terrible for folks with motion sickness.
That said it's not a long term solution (because honestly its frustrating due to losing a few hours during the work week, inability to drive, etc) so I'm working with Drs to actually resolve things without regularly being stabbed :D
There's also lozenge form which I believe some clinics allow you to take at home, but not sure of the effectiveness
Ketamine is supposed to be a disassociate drug, which I'm guessing is perhaps like an out of body experience or something. But I cant see how that can help with depression when people dont understand depression can actually be lots of things, but it has one overriding common element which is people remembering.
So unless people get something like dementia where recent memories seem to fade first and the earliest memories come back, I fail to see how K can help treat depression.
As for suicide ideation, well look around at what constitutes 1st world medical care! If you dont buy into the smiley faces because you might have grown up around medical professionals and heard the back office chats you might think twice about the authenticity of so called medical professionals! Not only that, its just a job for most, leave it at the door when your shift finishes, which is easier said than done especially if a dying patient seemed nice and innocent compared to an unpleasant angry dying patient.
I really dont know why we dont have legal euthanasia because being experimented on in the name of science is not something I'd let others do to me if I can help it, I am aware that some argue it would be a direction towards eugenics, but that goes on already in stealth with some medical procedures.
Obviously (going off things like trainspotting and peoples accounts), opiates are supposed to give you a warm fuzzy feeling as you slip into a deep sleep or unconsciousness I guess but not to sure, never done it not even in an operating theatre.
MAOI's the old style anti depressants are quite sudden in that they are like an on off switch for the brain, you dont remember or feel nothing and I think they were popular with people who wanted to end it, but SSRI's have replaced them as the new anti depressant treatment but their problem is you dont sleep properly on them so they introduce their own problems, but I'm not aware of any end of life properties in SSRI's other than they ruin your sleep and send you off the rails slowly.
But all the while, these chemicals still dont address the fundamental problem with depression which is remembering stuff that causes depression. Maybe depression should be treated more like PTSD, because depression seems to be an ego thing, where as talking to other people, PTSD seems to be more like what people associate as depression.
For bloke's I think the bio mechanical properties of testosterone would help many with PTSD, cant comment for women though, but the risk the police and medical lot dont want is some hulk losing it so the idea isnt entertained AFAIK.
Self preservation of institutions comes before everything else!
Edit: I should add, once CO2 blood saturation exceeds 30% it has a noble gas effect on the body, so anyone who remembers the periodic table should remember what noble gasses are and its why compressed gas companies go to great lengths to not enable pure noble gases getting into the hands of the public.
Biology and chemistry is just the mammalian equivalent of computer hacking.