5 ms·

> placebo that turned out to be escitalopram, an SSRI antidepressant. How is this a placebo?

BossingAround 5y ago
If that was sugar, it's pretty easy for me, as a study participant, to tell whether I've been given mushrooms or not (i.e. am I feeling drugged or not). I suspect that played a part of the reasoning to use a psychoactive compound instead of sugar pills as a placebo.
- TheBlight 5y ago
  IIRC, AstraZeneca did a similar thing when testing their covid-19 shots. In one of their trials the placebo was a meningitis vaccine.
  - cnity 5y ago
    Isn't the term "control" more accurate than "placebo" in these contexts? I thought that a placebo was inactive, while a control is used to set a baseline for judging improvement. A placebo is a type of control, but not vice versa.
    - bragr 5y ago
      A placebo doesn't have to be inert, it's more that it has to have no therapeutic value. Meningitis vaccine doesn't protect against covid so it's an effective placebo for testing covid vaccine for example.
    - arghwhat 5y ago
      A placebo does not need to be completely inactive, it merely needs to not exhibit the effect you are trying to test for. Using an anti-depressant as placebo for a test regarding anti-depressive effects does seem a bit odd, but it is fine if the test is for effects or durations exceeding the capability of placebo drugs.
- linguistbreaker 5y ago
  I think other studies have used Nicotine and other substances to provide an initial flush of feeling like you took something. That being said, "feeling drugged" is pretty dose dependent so plenty of studies could use a truly inactive placebo alongside a lower dose.
  - pmoriarty 5y ago
    "I think other studies have used Nicotine and other substances to provide an initial flush of feeling like you took something." Niacin, not nicotine. See the so-called "niacin-flush" response: https://en.wikipedia.org/wiki/Niacin#Flushing https://en.wikipedia.org/wiki/Niacin#Flushing
weego 5y ago
My assumption and this article is badly worded. The wording suggests the second group are not treatment-resistant, and considering the loading and expected timeline of any kind of effect of Escitalopram it may well have been their current medication. Especially as from my experience loading an SSRI has a very unmistakable physical unpleasantness which would be a give-away. There's also the ethical limitations of taking someone off a medication they need for their wellbeing to try something else, which is largely not allowed which makes trialing certain alternatives difficult and complex.
luto 5y ago
These days many studies use existing medicines as a placebo as opposed to just nothing in the form of sugar. see also https://en.wikipedia.org/wiki/Placebo#In_research_trials https://en.wikipedia.org/wiki/Placebo#In_research_trials
- meowface 5y ago
  If it's a psychoactive molecule, it's not really a placebo, in my opinion. I don't think the section you linked refutes this: >Some suggest that existing medical treatments should be used instead of placebos, to avoid having some patients not receive medicine during the trial. It discusses medical treatments used instead of placebos, rather than as placebos. I think the more accurate term here would be "control", not "placebo". It arguably could create or enhance a placebo effect with respect to psilocybin, but I think "control" would be less confusing terminology to refer to the non-psilocybin substance. Then again, they're the research university and I'm a random internet commenter, so they probably have more authority on this than I do.
  - tokai 5y ago
    Your opinion is not worth anything regarding this, as it goes against the common understanding of reseachers. The concept of an active placebo is from the 60s and is well know in medical studies.
    - meowface 5y ago
      My understanding is that an active placebo generates some expected effects so that the patient is more likely to believe that they took something: https://en.wikipedia.org/wiki/Active_placebo https://en.wikipedia.org/wiki/Active_placebo >An active placebo is a placebo that produces noticeable side effects that may convince the person being treated that they are receiving a legitimate treatment, rather than an ineffective placebo. >An example of an active placebo is the 1964 work of Shader and colleagues who used a combination of low-dose phenobarbital plus atropine to mimic the sedation and dry mouth produced by phenothiazines. >Morphine and gabapentin are painkillers with the common side effects of sleepiness and dizziness. In a 2005 study assessing the effects of these painkillers on neuropathic pain, lorazepam was chosen as an active placebo because it is not a painkiller but it does cause sleepiness and can cause dizziness. Here, it seems like an example active placebo might be something that induces nausea, since psilocybin is known to induce nausea. SSRIs are not just an active placebo but something that actually attempts to treat the primary symptom: depression. The above paragraph suggests lorazepam would be a good active placebo for testing painkillers because it is not a painkiller; here, an antidepressant is being compared with an antidepressant. So I was wrong to say that it's not a placebo if it's a psychoactive molecule. I just don't think it is if it's a psychoactive molecule that's treating the primary symptom you're attempting to find a treatment for.
macksd 5y ago
To help keep it as blind as possible, studies sometimes use something that is better understood and gives you the side-effects you might expect if you weren't on the placebo. Like the Pfizer COVID study used the meningitis vaccine as a placebo IIRC. edit: see another comment suggesting that control is the right term for this rather than placebo - face palm moment.
isoprophlex 5y ago
I guess it's poorly or incompletely worded. This is an "active placebo". Another example would be determining something about mystic experiences and testing amphetamine against psilocybin. You need something active, because otherwise even a drug-naive participant quickly groks they're on sugar and not an actual drug
luckydata 5y ago
placebo controlled studies are not really possible for psychedelics anyways. There's literally no way someone takes a high dose of it and doesn't figure out they have taken psychedelics. You need slightly different tools for this type of studies so I think they are comparing effectiveness instead.
- pmoriarty 5y ago
  Actually, I've heard a researcher say that in the MDMA studies they ran, some people who were given placebos experienced a full breakthrough, with lots of emotion, crying, and therapeutic benefit and swore that they were given MDMA. It probably also helped that these were people who'd never tried MDMA.. so they didn't really know what to expect. Also, in microdosing studies, I think even sugar pills could be very effective placebos.
PragmaticPulp 5y ago
Technically an "active control", though the patients appear to be selected to have been SSRI-resistant: > The open-label trial had the additional criteria of TRD, as defined by no improvement despite multiple courses of antidepressant medication (mean = 4.6 ± 2.6 past medications; range, 2–11) If i'm reading the study properly (disclaimer: I may not be) then the patients in the open-label trial had already failed an average of 4.6 typical antidepressants. So it's unlikely that they'd be responding to a starter dose of another SSRI (10mg escitalopram, though some were on 20mg perhaps by body weight)

If that was sugar, it's pretty easy for me, as a study participant, to tell whether I've been given mushrooms or not (i.e. am I feeling drugged or not). I suspect that played a part of the reasoning to use a psychoactive compound instead of sugar pills as a placebo.

TheBlight 5y ago
IIRC, AstraZeneca did a similar thing when testing their covid-19 shots. In one of their trials the placebo was a meningitis vaccine.
- cnity 5y ago
  Isn't the term "control" more accurate than "placebo" in these contexts? I thought that a placebo was inactive, while a control is used to set a baseline for judging improvement. A placebo is a type of control, but not vice versa.
  - bragr 5y ago
    A placebo doesn't have to be inert, it's more that it has to have no therapeutic value. Meningitis vaccine doesn't protect against covid so it's an effective placebo for testing covid vaccine for example.
  - arghwhat 5y ago
    A placebo does not need to be completely inactive, it merely needs to not exhibit the effect you are trying to test for. Using an anti-depressant as placebo for a test regarding anti-depressive effects does seem a bit odd, but it is fine if the test is for effects or durations exceeding the capability of placebo drugs.
linguistbreaker 5y ago
I think other studies have used Nicotine and other substances to provide an initial flush of feeling like you took something. That being said, "feeling drugged" is pretty dose dependent so plenty of studies could use a truly inactive placebo alongside a lower dose.
- pmoriarty 5y ago
  "I think other studies have used Nicotine and other substances to provide an initial flush of feeling like you took something." Niacin, not nicotine. See the so-called "niacin-flush" response: https://en.wikipedia.org/wiki/Niacin#Flushing https://en.wikipedia.org/wiki/Niacin#Flushing

weego 5y ago

My assumption and this article is badly worded. The wording suggests the second group are not treatment-resistant, and considering the loading and expected timeline of any kind of effect of Escitalopram it may well have been their current medication. Especially as from my experience loading an SSRI has a very unmistakable physical unpleasantness which would be a give-away. There's also the ethical limitations of taking someone off a medication they need for their wellbeing to try something else, which is largely not allowed which makes trialing certain alternatives difficult and complex.

luto 5y ago

These days many studies use existing medicines as a placebo as opposed to just nothing in the form of sugar. see also https://en.wikipedia.org/wiki/Placebo#In_research_trials https://en.wikipedia.org/wiki/Placebo#In_research_trials

meowface 5y ago
If it's a psychoactive molecule, it's not really a placebo, in my opinion. I don't think the section you linked refutes this: >Some suggest that existing medical treatments should be used instead of placebos, to avoid having some patients not receive medicine during the trial. It discusses medical treatments used instead of placebos, rather than as placebos. I think the more accurate term here would be "control", not "placebo". It arguably could create or enhance a placebo effect with respect to psilocybin, but I think "control" would be less confusing terminology to refer to the non-psilocybin substance. Then again, they're the research university and I'm a random internet commenter, so they probably have more authority on this than I do.
- tokai 5y ago
  Your opinion is not worth anything regarding this, as it goes against the common understanding of reseachers. The concept of an active placebo is from the 60s and is well know in medical studies.
  - meowface 5y ago
    My understanding is that an active placebo generates some expected effects so that the patient is more likely to believe that they took something: https://en.wikipedia.org/wiki/Active_placebo https://en.wikipedia.org/wiki/Active_placebo >An active placebo is a placebo that produces noticeable side effects that may convince the person being treated that they are receiving a legitimate treatment, rather than an ineffective placebo. >An example of an active placebo is the 1964 work of Shader and colleagues who used a combination of low-dose phenobarbital plus atropine to mimic the sedation and dry mouth produced by phenothiazines. >Morphine and gabapentin are painkillers with the common side effects of sleepiness and dizziness. In a 2005 study assessing the effects of these painkillers on neuropathic pain, lorazepam was chosen as an active placebo because it is not a painkiller but it does cause sleepiness and can cause dizziness. Here, it seems like an example active placebo might be something that induces nausea, since psilocybin is known to induce nausea. SSRIs are not just an active placebo but something that actually attempts to treat the primary symptom: depression. The above paragraph suggests lorazepam would be a good active placebo for testing painkillers because it is not a painkiller; here, an antidepressant is being compared with an antidepressant. So I was wrong to say that it's not a placebo if it's a psychoactive molecule. I just don't think it is if it's a psychoactive molecule that's treating the primary symptom you're attempting to find a treatment for.

macksd 5y ago

To help keep it as blind as possible, studies sometimes use something that is better understood and gives you the side-effects you might expect if you weren't on the placebo. Like the Pfizer COVID study used the meningitis vaccine as a placebo IIRC. edit: see another comment suggesting that control is the right term for this rather than placebo - face palm moment.

isoprophlex 5y ago

I guess it's poorly or incompletely worded. This is an "active placebo". Another example would be determining something about mystic experiences and testing amphetamine against psilocybin. You need something active, because otherwise even a drug-naive participant quickly groks they're on sugar and not an actual drug

luckydata 5y ago

placebo controlled studies are not really possible for psychedelics anyways. There's literally no way someone takes a high dose of it and doesn't figure out they have taken psychedelics. You need slightly different tools for this type of studies so I think they are comparing effectiveness instead.

pmoriarty 5y ago
Actually, I've heard a researcher say that in the MDMA studies they ran, some people who were given placebos experienced a full breakthrough, with lots of emotion, crying, and therapeutic benefit and swore that they were given MDMA. It probably also helped that these were people who'd never tried MDMA.. so they didn't really know what to expect. Also, in microdosing studies, I think even sugar pills could be very effective placebos.

PragmaticPulp 5y ago

Technically an "active control", though the patients appear to be selected to have been SSRI-resistant: > The open-label trial had the additional criteria of TRD, as defined by no improvement despite multiple courses of antidepressant medication (mean = 4.6 ± 2.6 past medications; range, 2–11) If i'm reading the study properly (disclaimer: I may not be) then the patients in the open-label trial had already failed an average of 4.6 typical antidepressants. So it's unlikely that they'd be responding to a starter dose of another SSRI (10mg escitalopram, though some were on 20mg perhaps by body weight)