8 ms·

> Then, patients received a first 40 minute intravenous infusion of ketamine (0.5 mg/kg) or placebo 0.9% (saline solution) in addition to their current treatmen

> Then, patients received a first 40 minute intravenous infusion of ketamine (0.5 mg/kg) or placebo 0.9% (saline solution) in addition to their current treatment. 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.

BurningFrog 5y ago
Injecting some other psychoactive drug should work, at least for patients who have never used ketamine before. But I suspect that would take many years to get through the permitting apparatus, if it was at all possible.
- after_care 5y ago
  Injecting someone with another psychoactive drug would not be a placebo. We would be comparing the efficacy of {other psychoactive drug} and ketamine. That's not to say this experiment has no value, it's one of the many experiments we should run to help build the case for ketamine. 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.
  - phren0logy 5y ago
    There is precedent for this; it's called "active placebo." For example, I think some of the psilocybin trials used methylphenidate as an active placebo comparison condition.
    - after_care 5y ago
      Sure, but as a scientist conducting an experiment I will be able to determine who is dosed with psilocybin and who is doses with methylphenidate >90% of the time, thus removing the observer mask. I think the average patient would be able to tell if they were dosed with psilocybin or methylphenidate, even if they were drug naive, thus removing the patient mask. 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.
      - phren0logy 5y ago
        The person assessing the depression response in the psilocybin studies is not in the room with the person while they are under the influence of the substance. The ratings are done on a different day. It's two different people to preserve blinding.
AdamH12113 5y ago
My psychiatrist administers IV ketamine treatments for depression. (I don't use those; regular antidepressants work for me.) I'm not sure what dosage she uses, but from what she's told me, it's not a drug trip, and a lot of people don't feel any different during the treatment. [Edited to clarify.]
- sandworm101 5y ago
  You might be in her placebo group.
  - aaaaaaaaata 5y ago
    I read it as their doctor receiving the treatment, not them.
    - sandworm101 5y ago
      "she uses" is an odd phrase for a patient. Patients normally "receive" or "are given". Drug addicts and doctors "use" a drug.
      - deleted 5y ago
        [deleted]
      - swores 5y ago
        Mmh, not sure. I received a prescription for a drug from my doctor, now I use (or 'take') that drug/medicine once a day. 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.
  - AdamH12113 5y ago
    Sorry, poor wording. I meant that my psychiatrist runs a ketamine clinic and administers IV ketamine treatments to patients.
hadmatter 5y ago
I’m sorry but you are strongly over exaggerating the (side) effects of i.v. ketamine. It’s not a dose that sends you in a K hole. It’s way less than that. Some get sedation and some do get dissociative symptoms which can unmask the study arm of the patient. Approximately one out of ten got at least one of those side effects. Sedation can be mimicked with midazolam, so if you use that as placebo, you get 90 % of the patients that are not obvious, which medicine they got. I do agree that a better ”placebo” would be good to 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. Of course if it would only alleviate suffering and wouldn’t increase the rate of suicides, that would be a win too.
- bradly 5y ago
  Inter muscular ketamine treatments were the only thing that helped my severe treatment resistant depression that included suicidal thoughts. They definitely had strong side affects. Complete disconnection, loss of the concept of humanism, I've gone inside a rainbow, held hands with my brain, etc..
- chimeracoder 5y ago
  > I’m sorry but you are strongly over exaggerating the (side) effects of i.v. ketamine. It’s not a dose that sends you in a K hole. It’s way less than that. 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
boomboomsubban 5y ago
>1.The nurse administering knew if it was placebo or active (for safety reasons). 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.
- btach 5y ago
  The nurse administering it is most certainly liable for what s/he administers. It is a very big no-no to blindly administer a medication of which you cannot reasonably verify what it is. To push a syringe or start a pump of something that "could be ketamine, or could be NS" is walking an uncomfortable line for your license to practice nursing. Right patient, right medication, right dose, right route, right time. If you as a nurse cannot attest to all of the above when you push something, it is in error to push it.
  - boomboomsubban 5y ago
    >Right patient, right medication, right dose, right route, right time 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.
    - s1artibartfast 5y ago
      The parent comment is absolutely correct. This is salt in the medical community by having a nurse that knows exactly what the patient is getting and a different clinician doing the assessment
  - throwaway81523 5y ago
    How does it work in other clinical trials where you take a pill instead of getting an injection? Those are double blind all the time. They watch you take the pill, but they don't know whether it is active or placebo. 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.
deleted 5y ago
[deleted]
PragmaticPulp 5y ago
0.5mg/kg spread out over 40 minutes wouldn’t be as dramatic as you’re suggesting. > 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.
- dwaltrip 5y ago
  My personal experience suggests otherwise. 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.
sonicggg 5y ago
Your second point does not invalidate it as a double blind. But I agree that the person administering should not be aware.
fsckboy 5y ago
> 2. It would immediately become obvious to the subject if they were injected with salt water or ketamine. 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.

BurningFrog 5y ago

Injecting some other psychoactive drug should work, at least for patients who have never used ketamine before. But I suspect that would take many years to get through the permitting apparatus, if it was at all possible.

after_care 5y ago
Injecting someone with another psychoactive drug would not be a placebo. We would be comparing the efficacy of {other psychoactive drug} and ketamine. That's not to say this experiment has no value, it's one of the many experiments we should run to help build the case for ketamine. 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.
- phren0logy 5y ago
  There is precedent for this; it's called "active placebo." For example, I think some of the psilocybin trials used methylphenidate as an active placebo comparison condition.
  - after_care 5y ago
    Sure, but as a scientist conducting an experiment I will be able to determine who is dosed with psilocybin and who is doses with methylphenidate >90% of the time, thus removing the observer mask. I think the average patient would be able to tell if they were dosed with psilocybin or methylphenidate, even if they were drug naive, thus removing the patient mask. 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.
    - phren0logy 5y ago
      The person assessing the depression response in the psilocybin studies is not in the room with the person while they are under the influence of the substance. The ratings are done on a different day. It's two different people to preserve blinding.

AdamH12113 5y ago

My psychiatrist administers IV ketamine treatments for depression. (I don't use those; regular antidepressants work for me.) I'm not sure what dosage she uses, but from what she's told me, it's not a drug trip, and a lot of people don't feel any different during the treatment. [Edited to clarify.]

sandworm101 5y ago
You might be in her placebo group.
- aaaaaaaaata 5y ago
  I read it as their doctor receiving the treatment, not them.
  - sandworm101 5y ago
    "she uses" is an odd phrase for a patient. Patients normally "receive" or "are given". Drug addicts and doctors "use" a drug.
    - deleted 5y ago
      [deleted]
    - swores 5y ago
      Mmh, not sure. I received a prescription for a drug from my doctor, now I use (or 'take') that drug/medicine once a day. 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.
- AdamH12113 5y ago
  Sorry, poor wording. I meant that my psychiatrist runs a ketamine clinic and administers IV ketamine treatments to patients.

hadmatter 5y ago

I’m sorry but you are strongly over exaggerating the (side) effects of i.v. ketamine. It’s not a dose that sends you in a K hole. It’s way less than that. Some get sedation and some do get dissociative symptoms which can unmask the study arm of the patient. Approximately one out of ten got at least one of those side effects. Sedation can be mimicked with midazolam, so if you use that as placebo, you get 90 % of the patients that are not obvious, which medicine they got. I do agree that a better ”placebo” would be good to 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. Of course if it would only alleviate suffering and wouldn’t increase the rate of suicides, that would be a win too.

bradly 5y ago
Inter muscular ketamine treatments were the only thing that helped my severe treatment resistant depression that included suicidal thoughts. They definitely had strong side affects. Complete disconnection, loss of the concept of humanism, I've gone inside a rainbow, held hands with my brain, etc..
chimeracoder 5y ago
> I’m sorry but you are strongly over exaggerating the (side) effects of i.v. ketamine. It’s not a dose that sends you in a K hole. It’s way less than that. 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

boomboomsubban 5y ago

>1.The nurse administering knew if it was placebo or active (for safety reasons). 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.

btach 5y ago
The nurse administering it is most certainly liable for what s/he administers. It is a very big no-no to blindly administer a medication of which you cannot reasonably verify what it is. To push a syringe or start a pump of something that "could be ketamine, or could be NS" is walking an uncomfortable line for your license to practice nursing. Right patient, right medication, right dose, right route, right time. If you as a nurse cannot attest to all of the above when you push something, it is in error to push it.
- boomboomsubban 5y ago
  >Right patient, right medication, right dose, right route, right time 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.
  - s1artibartfast 5y ago
    The parent comment is absolutely correct. This is salt in the medical community by having a nurse that knows exactly what the patient is getting and a different clinician doing the assessment
- throwaway81523 5y ago
  How does it work in other clinical trials where you take a pill instead of getting an injection? Those are double blind all the time. They watch you take the pill, but they don't know whether it is active or placebo. 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.

deleted 5y ago

[deleted]

PragmaticPulp 5y ago

0.5mg/kg spread out over 40 minutes wouldn’t be as dramatic as you’re suggesting. > 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.

dwaltrip 5y ago
My personal experience suggests otherwise. 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.

sonicggg 5y ago

Your second point does not invalidate it as a double blind. But I agree that the person administering should not be aware.

fsckboy 5y ago

> 2. It would immediately become obvious to the subject if they were injected with salt water or ketamine. 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.