FDA advisory panel votes against approving MDMA-assisted therapy for PTSD

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clozareal

clozareal

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I wanted to get this discussion started because it's an interesting one. The FDA advisory panel rejected MDMA-assisted therapy for PTSD had an issue with functional unblinding, cardiovascular risk, therapist misconduct/sexual assault, and lack of data on dependence risk. The rejection wasn't just for MDMA, it was for MDMA-assisted psychotherapy.

I think it's very disappointing that this was not approved as I think treatment for PTSD is sorely needed.

It's kind of strange that Lykos wanted to approve a brand new, manualized psychotherapy for PTSD when the FDA doesn't regulate therapy. If they would have just went the route of Suboxone, where the FDA indication is "should be used as part of a complete treatment plan that includes counseling and psychosocial support" that would have been much better. They should have just had Cognitive Processing Therapy or Prolonged Exposure, the gold standards for PTSD, be the therapy arm rather than trying to push through a new drug and a new psychotherapy simultaneously, both of which are untested. The study design them becomes too muddled.

They did a disservice to those with PTSD with this study design and pushing for the FDA to approve a type of psychotherapy, rather than just a drug which is what they do.

What do you all think?
 
Probably wanted to get double the $$ by being able to sell the drug and the therapy.
 
I think it's worth reading how we historically used MDMA as psychiatrists.

Now I suspect It would quickly become a slippery slope and midlevel providers would start opening up MDMA pill mills left and right.

FDA and other 3 letter agencies are being more cautious with scheduled meds as they have noticed that once regulations are relaxed by a small margin it can quickly become messy.
 
clozareal said:
I think it's very disappointing that this was not approved as I think treatment for PTSD is sorely needed.
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I vehemently disagree. We have more than enough effective treatments for PTSD.

My hot take: Even if MDMA works for PTSD, the harms of approving it as a treatment would dramatically outweigh the benefits.
 
I tend to also think the harms could be extreme. I'm all for decriminalization, but that does not mean it is effective or helpful. I'm just not sure where the logic of using a dissociative agent to treat avoidant disorders like PTSD comes in...
 
The treatment for PTSD should be to stop creating PTSD in the first place - stop sending Americans abroad to fight useless wars who will then require life-long and costly treatment (and it is doubtful that this treatment will even be available to them)
 
allantois said:
The treatment for PTSD should be to stop creating PTSD in the first place - stop sending Americans abroad to fight useless wars who will then require life-long and costly treatment (and it is doubtful that this treatment will even be available to them)
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This is prevention rather than treatment. Focusing on treatment doesn't mean we can't also address prevention.
 
allantois said:
The treatment for PTSD should be to stop creating PTSD in the first place - stop sending Americans abroad to fight useless wars who will then require life-long and costly treatment (and it is doubtful that this treatment will even be available to them)
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That doesn't really help the millions of people that are sexually assaulted and raped here. Just because the research is mostly conducted in the VA doesn't mean that's the only form of trauma being treated. Many of the veterans I worked with in residency had PTSD from childhood traumas and the reported traumas from military weren't the actual cause of their ongoing problems.
 
aim-agm said:
I vehemently disagree. We have more than enough effective treatments for PTSD.

My hot take: Even if MDMA works for PTSD, the harms of approving it as a treatment would dramatically outweigh the benefits.
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We have 2 FDA approved medications that don't really work that much better than therapy, one of which we don't even use much in psychiatry (paroxetine, sertraline). There's a few more that aren't FDA approved but seem slightly better than placebo for PTSD too (venlafaxine, prazosin). We don't nearly have as much effective medication options for PTSD as many other psychiatric conditions.
 
clozareal said:
We have 2 FDA approved medications that don't really work that much better than therapy, one of which we don't even use much in psychiatry (paroxetine, sertraline). There's a few more that aren't FDA approved but seem slightly better than placebo for PTSD too (venlafaxine, prazosin). We don't nearly have as much effective medication options for PTSD as many other psychiatric conditions.
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1) Start with SRI+sympatholytic
2) If you need to augment, buspirone and/or NRI

Most PTSD patients don't even need to go to step 2. Rarely do I have to go beyond step 2.
 
The VAST majority of PTSD, including in veterans, is not combat related. Most veterans were not involved in combat, even those serving at the height of the Gulf Wars. Stopping wars will help, but certainly not prevent, PTSD. (Also, we're not stopping wars.)
 
comp1 said:
The VAST majority of PTSD, including in veterans, is not combat related. Most veterans were not involved in combat, even those serving at the height of the Gulf Wars. Stopping wars will help, but certainly not prevent, PTSD. (Also, we're not stopping wars.)
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Waiting on @Sushirolls political comment on our military industrial complex.
 
comp1 said:
The VAST majority of PTSD, including in veterans, is not combat related. Most veterans were not involved in combat, even those serving at the height of the Gulf Wars. Stopping wars will help, but certainly not prevent, PTSD. (Also, we're not stopping wars.)
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In fact some studies suggest that veterans who were not involved in combat roles were actually more likely to develop PTSD.
 
littlefred said:
I think it's worth reading how we historically used MDMA as psychiatrists.

Now I suspect It would quickly become a slippery slope and midlevel providers would start opening up MDMA pill mills left and right.

FDA and other 3 letter agencies are being more cautious with scheduled meds as they have noticed that once regulations are relaxed by a small margin it can quickly become messy.
Click to expand...
I don't know, the REMS system for Spravato seems to be very secure with keeping it off the streets/regularly ingested. Why would this be any different? I apologize as I am not tracking it closely, my understanding is this would be only used in a therapeutic setting rather than take 1 molly QD #30.
 
This has been challenging for me clinically because very rarely do I find just PTSD without some co-morbidity involving personality (self/other). This has been called so many things: Co-morbid BPD, Co-morbid moderate-severe personality disorder (DSM-5 Alternate System), Dysregulated self-organization (DSO), "C" PTSD, or DSM IV PTSD + 3 BPD criteria, etc.

Continuing to just call this PTSD is misleading. Very often, I do exposure therapy (WET) with patients, and on their 2nd session, they actually want to write/talk about their family neglect; what really bothers them is developmental invalidation. Or, when going through the PTSD criteria, they fail to associate it with "the trauma" and, instead, relate it to their boyfriend breaking up with them that same week.

This other stuff requires longer-term psychotherapy. Is that PTSD refractory, or is there more to the formulation? They probably also have "treatment-resistant depression" too!
 
Yeah, I always get flustered when people strongly associate combat with PTSD. They aren't synonymous. They are related as combat could be a Criterion A, but still quite loosely and yes, there definitely are studies that show some protective effect due to various psychosocial factors relative to veterans who did not participate in combat when you carefully control.
 
aim-agm said:
This is because I am good at treating PTSD.
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I'm sorry, but your claim that your patients get better because you're that good and while simultaneously claiming that most don't even need more than an SRI + sympatholytic just doesn't match up with the reality of actual PTSD patients unless you're the one doing extensive therapy with them and are that good at therapy. If SRIs + some prazosin or clonidine was that effective then psychedelic research would be irrelevant. Also, buspirone sucks for PTSD. Idk that I've ever had a patient where PTSD was the real issue who felt buspirone was helpful at all.

Merovinge said:
I don't know, the REMS system for Spravato seems to be very secure with keeping it off the streets/regularly ingested. Why would this be any different? I apologize as I am not tracking it closely, my understanding is this would be only used in a therapeutic setting rather than take 1 molly QD #30.
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Spravato isn't the issue. It's compounded ketamine and all the IV infusion clinics offering IV ketamine where the problems arise, as they're not included in REMS programs and being schedule III means there's less scrutiny and regulation surrounding their prescribing.
 
comp1 said:
Yeah, I always get flustered when people strongly associate combat with PTSD. They aren't synonymous. They are related as combat could be a Criterion A, but still quite loosely and yes, there definitely are studies that show some protective effect due to various psychosocial factors relative to veterans who did not participate in combat when you carefully control.
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I recognize that most of the veteran PTSD is not combat related; nevertheless they report trauma directly related to their military service
 
allantois said:
I recognize that most of the veteran PTSD is not combat related; nevertheless they report trauma directly related to their military service
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Yes, because that's how they get service connection. Many veterans without any trauma disorder do this to get SC also. This has been discussed extensively and SC should not be seen as reflective of actual MH conditions.
 
Merovinge said:
I don't know, the REMS system for Spravato seems to be very secure with keeping it off the streets/regularly ingested. Why would this be any different? I apologize as I am not tracking it closely, my understanding is this would be only used in a therapeutic setting rather than take 1 molly QD #30.
Click to expand...
My argument is not for street use, it's for unscrupulous prescribers. Read my post again.

You're going to tell me with a straight face that all Ketamine and Esketamine providers out there are psychiatrists following strict FDA indications?
 
romanticscience said:
This has been challenging for me clinically because very rarely do I find just PTSD without some co-morbidity involving personality (self/other). This has been called so many things: Co-morbid BPD, Co-morbid moderate-severe personality disorder (DSM-5 Alternate System), Dysregulated self-organization (DSO), "C" PTSD, or DSM IV PTSD + 3 BPD criteria, etc.

Continuing to just call this PTSD is misleading. Very often, I do exposure therapy (WET) with patients, and on their 2nd session, they actually want to write/talk about their family neglect; what really bothers them is developmental invalidation. Or, when going through the PTSD criteria, they fail to associate it with "the trauma" and, instead, relate it to their boyfriend breaking up with them that same week.

This other stuff requires longer-term psychotherapy. Is that PTSD refractory, or is there more to the formulation? They probably also have "treatment-resistant depression" too!
Click to expand...
Complex PTSD looks a lot like BDP for some reason in a signifcant portion of patients I treat, don't know why...when I go through developmental/past history, it doesn't seem like they HAD BPD, but they seem to develop it after intense PTSD, or maybe I am missing something. Curious to hear what other providers noticed, in relation to personality disorders before and after PTSD.
 
littlefred said:
My argument is not for street use, it's for unscrupulous prescribers. Read my post again.

You're going to tell me with a straight face that all Ketamine and Esketamine providers out there are psychiatrists following strict FDA indications?
Click to expand...
I agree with you on the ketamine. I don't know, are unscrupulous people really bothering with Spravato? Insurance is very particular about covering it and I would think everyone who is exploring it off label is going for the ketamine. I've never prescribed either drug. I was under the impression the REMS for Spravato was a good thing, even if the vital signs monitoring is a little excessive.
 
Stagg737 said:
I'm sorry, but your claim that your patients get better because you're that good and while simultaneously claiming that most don't even need more than an SRI + sympatholytic just doesn't match up with the reality of actual PTSD patients unless you're the one doing extensive therapy with them and are that good at therapy. If SRIs + some prazosin or clonidine was that effective then psychedelic research would be irrelevant. Also, buspirone sucks for PTSD. Idk that I've ever had a patient where PTSD was the real issue who felt buspirone was helpful at all.
Click to expand...
I admit that a significant part of the intent of that response was not to imply that I'm "that good" but to imply that the person who was disparaging my clinical skills and experience was "not good."

I can only speak to my reality of numerous actual PTSD patients, and I my statements are truthful to that reality.

I should clarify that sympatholytic includes alpha-2 agonists. I suspect much of my relative success relates to being more willing to use that medication class. However, even if they aren't typically used, alpha-2s are many decades old and are a well established part of the psychiatric repertoire. But even prazosin is often too narrowly utilized, as it can be quite effective for daytime symptoms but is typically only used for sleep/nightmares.

I also would not be surprised if my psychotherapeutic interventions (usually not extensive) facilitate success of the medications, but that is irrelevant to my point that we don't need new PTSD meds. We might need better access to reliably good therapy, but MDMA wouldn't obviate that issue (and would probably worsen it by diluting the pool of therapists with hacks offering MDMA-assisted therapy).

In my experience buspirone has usually been quite helpful for PTSD, although certainly a good number of patients don't benefit. I am a careful diagnostician and am selective with my PTSD diagnosis. I'm not sure why we have different experiences.
 
aim-agm said:
I admit that a significant part of the intent of that response was not to imply that I'm "that good" but to imply that the person who was disparaging my clinical skills and experience was "not good."

I can only speak to my reality of numerous actual PTSD patients, and I my statements are truthful to that reality.

I should clarify that sympatholytic includes alpha-2 agonists. I suspect much of my relative success relates to being more willing to use that medication class. However, even if they aren't typically used, alpha-2s are many decades old and are a well established part of the psychiatric repertoire. But even prazosin is often too narrowly utilized, as it can be quite effective for daytime symptoms but is typically only used for sleep/nightmares.

I also would not be surprised if my psychotherapeutic interventions (usually not extensive) facilitate success of the medications, but that is irrelevant to my point that we don't need new PTSD meds. We might need better access to reliably good therapy, but MDMA wouldn't obviate that issue (and would probably worsen it by diluting the pool of therapists with hacks offering MDMA-assisted therapy).

In my experience buspirone has usually been quite helpful for PTSD, although certainly a good number of patients don't benefit. I am a careful diagnostician and am selective with my PTSD diagnosis. I'm not sure why we have different experiences.
Click to expand...
I don't recall anyone in this thread coming anywhere near accusing you of having poor clinical skills. Where did you get that from?
 
Concur, service connected disabilities should not generally be utilized diagnostically for treatment. The VHA and VBA may be under the VA, but they are separate entities with unique goals and criteria. In general, it should be a one way street in terms of clinical information. The VBA uses clinical info from the VHA (per their own policy), but not vice-versa. Service connection for PTSD or any other condition should not necessarily guide clinical treatment. Letting service connection guide treatment can lead to perverse incentives about recovery. And again, even that service connected PTSD is not related to combat in most cases.
 
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comp1 said:
I tend to also think the harms could be extreme. I'm all for decriminalization, but that does not mean it is effective or helpful. I'm just not sure where the logic of using a dissociative agent to treat avoidant disorders like PTSD comes in...
Click to expand...
Would definitely not call MDMA a dissociative
 
clozareal said:

I wanted to get this discussion started because it's an interesting one. The FDA advisory panel rejected MDMA-assisted therapy for PTSD had an issue with functional unblinding, cardiovascular risk, therapist misconduct/sexual assault, and lack of data on dependence risk. The rejection wasn't just for MDMA, it was for MDMA-assisted psychotherapy.

I think it's very disappointing that this was not approved as I think treatment for PTSD is sorely needed.

It's kind of strange that Lykos wanted to approve a brand new, manualized psychotherapy for PTSD when the FDA doesn't regulate therapy. If they would have just went the route of Suboxone, where the FDA indication is "should be used as part of a complete treatment plan that includes counseling and psychosocial support" that would have been much better. They should have just had Cognitive Processing Therapy or Prolonged Exposure, the gold standards for PTSD, be the therapy arm rather than trying to push through a new drug and a new psychotherapy simultaneously, both of which are untested. The study design them becomes too muddled.

They did a disservice to those with PTSD with this study design and pushing for the FDA to approve a type of psychotherapy, rather than just a drug which is what they do.

What do you all think?
Click to expand...
Disappointing, but completely agree with your analysis that linking the drug to an untested therapeutic approach in retrospect was not a very clever way to go about this.

Also agree with the panel that the apparent sexual approach to a participant?? By the therapists???? is super concerning and merits putting the brakes on until appropriate safeguards can be devised against this type of situation.

The functional unblinding is I think sort of a Duh, and also a Who Cares? If the subjective experience is a critical part of the mechanism then complete, unassailable blinding isn't an appropriate or relevant expectation.
 
I have read many opinions about the decision, but this is, in my opinion, the best synopsis I have seen. It also addresses many of the issues mentioned in this thread.
1717726141885.png
 
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ClosetCentrist said:
Would definitely not call MDMA a dissociative
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Uh, what? Whether you look at it from a research/clinical or recreational aspect it is absolutely a dissociative agent.

ObsequiousAplomb said:
I agree with you on the ketamine. I don't know, are unscrupulous people really bothering with Spravato? Insurance is very particular about covering it and I would think everyone who is exploring it off label is going for the ketamine. I've never prescribed either drug. I was under the impression the REMS for Spravato was a good thing, even if the vital signs monitoring is a little excessive.
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I think LF is talking about PO or IV ketamine which is not monitored through REMS and is only schedule III. Plenty of shady prescribers out there using oral ketamine via lozenges or troches. REMS and in-clinic monitoring for Spravato and IV ketamine is a good thing IMO, but again I don't think that's what Fred is talking about.
 
tr said:
Disappointing, but completely agree with your analysis that linking the drug to an untested therapeutic approach in retrospect was not a very clever way to go about this.

Also agree with the panel that the apparent sexual approach to a participant?? By the therapists???? is super concerning and merits putting the brakes on until appropriate safeguards can be devised against this type of situation.

The functional unblinding is I think sort of a Duh, and also a Who Cares? If the subjective experience is a critical part of the mechanism then complete, unassailable blinding isn't an appropriate or relevant expectation.
Click to expand...
Yea, I won't comment on this further publicly, but I just saw did some reading on this decision and can say that some of the "experts" advising on this are absolutely not experts in the area of psychedelics or mental health at all. Frankly, they have no business making official comments in this area at all.
 
clozareal said:
It's kind of strange that Lykos wanted to approve a brand new, manualized psychotherapy for PTSD when the FDA doesn't regulate therapy. If they would have just went the route of Suboxone, where the FDA indication is "should be used as part of a complete treatment plan that includes counseling and psychosocial support" that would have been much better. They should have just had Cognitive Processing Therapy or Prolonged Exposure, the gold standards for PTSD, be the therapy arm rather than trying to push through a new drug and a new psychotherapy simultaneously, both of which are untested. The study design them becomes too muddled.
Click to expand...
It's not strange at all. MDMA is not suboxone. The whole point is that you aren't using the drug as a medication but to facilitate a therapeutic experience and inner healing. This is not compatible with CPT or PE etc although exposure is a part of this therapy. Without the psychotherapeutic component, you wouldn't have a new treatment for PTSD at all. The therapy is heavily, heavily influenced by Stanislov Grof's LSD psychotherapy and then seems to draw from humanistic, psychodynamic, cognitive, behavioral, somatic, and parts approaches.

You're taking a more medicalized approach which is anti-thetical to how proponents have envisioned MDMA-AP. Interestingly the biological psychiatrists have been questioning whether psychotherapy is necessary to unlock the therapeutic benefits of psychedelics, but most people who have been interested in this area (especially the non-physicians) have been interested in psychedelics primarily because they are not seen as a technomedical intervention but facilitative of transformative inner healing. From a marxist perspective, the role of psychiatry has been to oppress and regulate the masses and manage subjectivity whereas the proposed role of psychedelics is to liberate the masses and unravel subjectivity. The backlash against psychdelics (which also consigned research to the scrap heap for 40 years) was in part a response to the potential destabilizing impact of psychedelics on late capitalism.

All of this of course is not conducive to the FDA approval process. I think many people have been put off by the cult-like aspects of psychedelic assisted therapy movement, and some of the dominating personalities. In order to get this through the process, there was always going to be a higher standard and there are enough yellow flags to raise concern.

My main concern is how VC and tech companies are going to ruin this. I am excited for the potential of MDMA-AP for my somatoform pts but we really have to get this right. Ironically, last time it was the hippies everyone was afraid. This time it's venture capitalists we should be afraid of.
 
splik said:
It's not strange at all. MDMA is not suboxone. The whole point is that you aren't using the drug as a medication but to facilitate a therapeutic experience and inner healing. This is not compatible with CPT or PE etc although exposure is a part of this therapy. Without the psychotherapeutic component, you wouldn't have a new treatment for PTSD at all.
Click to expand...
From a treatment perspective this totally makes sense, and has seemed logical for as long as I've been following this story.

But from the perspective of trying to get a therapeutic approval for a potential drug of abuse past the government regulators, in retrospect it gave them a whole other target to shoot at.

Practically it would have made more sense to just combine with CPT to avoid opening that can of worms. Agree that effect size might be smaller, it seems possible that people on MDMA just wouldn't want to engage with traditional exposure therapies while in that mindset. But given the astounding effect sizes seen, I think they still would have easily surpassed the significance bar for most of our existing therapeutic options.
 
psych_0 said:
I have read many opinions about the decision, but this is, in my opinion, the best synopsis I have seen. It also addresses many of the issues mentioned in this thread.
View attachment 387747
Click to expand...

I think this opinion underplays the psychotherapist ethics issue.

Yes regulatory bodies for this exist. But none of them are designed to cover instances in which the patient has their interpersonal judgement and threat alert mechanisms so globally altered as with MDMA.

It's another ballgame entirely and I have to agree that the two-therapist approach taken so far seems to have failed in this instance, suggesting that more thought about this is needed.
 
thelastpsych said:
Complex PTSD looks a lot like BDP for some reason in a signifcant portion of patients I treat, don't know why...when I go through developmental/past history, it doesn't seem like they HAD BPD, but they seem to develop it after intense PTSD, or maybe I am missing something. Curious to hear what other providers noticed, in relation to personality disorders before and after PTSD.
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Yes. I think that may be what elements of borderline organization J. Herman was trying to emphasize in CPTSD/DESNOS, the impairments in identity, affect regulation, and relationships. These individuals are not so angry, relationally chaotic, or self-injurious. I think the key ingredient here, and DSM-5 incorporated it, is dissociation (the dissociative subtype of PTSD was partially a concession to the appeal to add CPTSD alongside PTSD, along with adding symptoms of negative affects and cognition).

I've been trying to further understand the relationship between dissociation and childhood sexual abuse. There is some research to endorse it's not the trauma per se that's driving the dissociation (1). In these cases, as you mention about the personal symptoms evolving after the trauma, the person's reaction is mediated by the family environment.

1. Draijer, N. & Langeland, W. Childhood Trauma and Perceived Parental Dysfunction in the Etiology of Dissociative Symptoms in Psychiatric Inpatients. Am. J. Psychiatry 156, 379–385 (1999).
 
tr said:
Disappointing, but completely agree with your analysis that linking the drug to an untested therapeutic approach in retrospect was not a very clever way to go about this.

Also agree with the panel that the apparent sexual approach to a participant?? By the therapists???? is super concerning and merits putting the brakes on until appropriate safeguards can be devised against this type of situation.

The functional unblinding is I think sort of a Duh, and also a Who Cares? If the subjective experience is a critical part of the mechanism then complete, unassailable blinding isn't an appropriate or relevant expectation.
Click to expand...

But the unblinding is pretty critical if you want to make an argument that this particular molecule of interest is driving the effect rather than just incredibly strong expectancies. Especially given the highly self -selected population of people volunteering for psychedelic experiments.
 
Merovinge said:
I don't know, the REMS system for Spravato seems to be very secure with keeping it off the streets/regularly ingested. Why would this be any different? I apologize as I am not tracking it closely, my understanding is this would be only used in a therapeutic setting rather than take 1 molly QD #30.
Click to expand...

Agreed. I think Spravato and in-office ketamine is going fine. The biggest issue I have is the mail order venture capital groups. This is why we need Ryan Haight laws back. We can’t keep nice things.

I don’t see why MDMA with REMS would be a problem.
 
tr said:
Yes regulatory bodies for this exist. But none of them are designed to cover instances in which the patient has their interpersonal judgement and threat alert mechanisms so globally altered as with MDMA.
Click to expand...

Certainly true. My guess is that the responsibility for this would ultimate fall to the liability coverage providers.
 
There might be more dissociative drugs out there, but MDMA, quite simply, is a dissociative. As they said in the hearing, the FDA has limited authority to require that psychotherapy be performed during MDMA administration and even less ability actually enforce such a requirement and/or monitor quality if they did somehow craft a requirement. Once MDMA gets off Schedule I, it's a free for all. As such, these drugs that really need a psychotherapy intervention along with administration really do have a higher bar to clear showing large benefit to outweigh the clear risk.
 
TexasPhysician said:
Agreed. I think Spravato and in-office ketamine is going fine. The biggest issue I have is the mail order venture capital groups. This is why we need Ryan Haight laws back. We can’t keep nice things.

I don’t see why MDMA with REMS would be a problem.
Click to expand...
Right as if Adderall 20mg TID IR only pill mill weren't a problem enough, we have mail order Special K to keep you fully dissociated at all times. Thanks VC!
 
clausewitz2 said:
But the unblinding is pretty critical if you want to make an argument that this particular molecule of interest is driving the effect rather than just incredibly strong expectancies. Especially given the highly self -selected population of people volunteering for psychedelic experiments.
Click to expand...
So if the concern is about expectancies in non-MDMA-naive patients, why not just look at the effect size in the MDMA-naive subset? It sounds like that was a good 60% of the participants. If the effect size in that subset is anywhere near as large as it was for the group overall, I just can't see the concern.

What would it even mean to say this is a placebo effect when it overwhelms the size of any placebo or active therapeutic effect ever studied? Making the case for placebo would require one to explain what is it about the MDMA 'placebo effect' that makes it so uniquely powerful vs any other agent ever studied, which is a more convoluted and less important question than just accepting the benefit for what it is and moving on to assess it against the risk side of the equation.
 
tr said:
So if the concern is about expectancies in non-MDMA-naive patients, why not just look at the effect size in the MDMA-naive subset? It sounds like that was a good 60% of the participants. If the effect size in that subset is anywhere near as large as it was for the group overall, I just can't see the concern.

What would it even mean to say this is a placebo effect when it overwhelms the size of any placebo or active therapeutic effect ever studied? Making the case for placebo would require one to explain what is it about the MDMA 'placebo effect' that makes it so uniquely powerful vs any other agent ever studied, which is a more convoluted and less important question than just accepting the benefit for what it is and moving on to assess it against the risk side of the equation.
Click to expand...

I agree that looking at only MDMA-naive patients certainly is helpful in addressing this concern, no doubt. But at the end of the day if participants can clearly tell they were in the treatment condition, there is a huge risk that they are going to answer questions in a way consistent with bigger symptom reduction than otherwise. Difficult as it is to do I think more studies with active placebos are desperately needed. I do understand the concerns that this may prove impossible to do perfectly but getting closer would help a lot.
 
clausewitz2 said:
I agree that looking at only MDMA-naive patients certainly is helpful in addressing this concern, no doubt. But at the end of the day if participants can clearly tell they were in the treatment condition, there is a huge risk that they are going to answer questions in a way consistent with bigger symptom reduction than otherwise. Difficult as it is to do I think more studies with active placebos are desperately needed. I do understand the concerns that this may prove impossible to do perfectly but getting closer would help a lot.
Click to expand...
Why does this only seemingly matter in psychedelic studies? I highly doubt people can't tell the difference between Zyprexa and docusate or whatever placebo we use in those studies.
 
how did they blind Auvelity, people must have felt the dxm
 
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