A series of posts have been moved from
Aripiprazole - Abilify
This is a bit harsh, I think. By a proper trial, I assume you mean a RCT trial?
Not specifically, just a trial that when looked at carefully in common sense terms provides evidence with a high probability of being meaningful. My proof of concept trial for rituximab in systemic autoimmune disease was uncontrolled and unrandomised, but because I had detailed pharmacodynamic profiles and objective endpoints it was sufficient to turn around the drug company from no interest to investing $2M in a bigger study. Everyone could see the results must mean something.
I spent much of my career involved in trials and what matters in the end is the likelihood, in common sense terms, that the results will stand up.
I agree that if you are a physician treating ME then a personal account of improvement while using e.g. aripiprazole should be a wake up call to see if that might mean something and maybe explore, discuss with the drug company, ask colleagues about experiences etc. My comment was in relation to us as forum users hearing of someone getting better while on a drug. The problem is that with a million or so people with ME with internet access someone with ME is bound to feel better while using aripiprazole, for whatever reason. And if others hear of that and ask to try some they may well get a placebo effect and so we end up with a rash of stories of improvement on the drug. I am the same physician who decided to investigate further in the clinic context, and one of my roles here is to pick up research ideas and try to persuade funders to take them seriously, but the stories of improvement on aripiprazole are no use to me in that regard - for the likelihood reason I have given. If OMF physicians think that the context merits investigation then hopefully they will do a useful trial, but their perspective will be different from ours.
Isn it not gaslighting to state that a patient is not improving on a med because the med has not undergone a controlled trial?
No. I think that is an unfair analysis that misses the point. I have not stated that patients are not getting better. A placebo response is getting better, so by definition I think they are. What I am unconvinced by is the assumption that they have got better because of that particular drug. We might well ask whether it matters if it its a placebo effect but the answer to that is that it does not matter much to that person but it does matter to everyone else because of the risks of psychotropic drugs (which include increased suicide risk, stroke from hypertensive crisis, permanent disfiguring involuntary movements, fetal abnormalities, etc, etc.).
I agree that endpoints matter, and deciding in advance what end-point you are going to take as evidence of true effect is crucial. The phase 2 open rituximab study is instructive because it showed that the placebo response followed what physicians and patients thought the time profile should be. The problem with invoking tachyphylaxis in ME is that it looks pretty much like what one would expect from fall off of placebo response. The irony of the phase 2 ritual trial was that the falloff of the placebo response was part of the placebo response because it was expected and another dose produced a new placebo response as expected. In other words the trial shows just how much suggestibility can come in to this. That is not gaslighting. It is documenting the way symptoms can go up and down.
I don't understand why there was a large placebo effect in the rituximab trial, but I worry that it may have poisoned the well for the UNCONTROLLED Norwegian cyclophosphamide trial, which had pretty spectacular treatment effects. I worry that patients and researchers lost faith in the UNCONTROLLED cyclo study because of the ritux study placebo effects. My point here is that the cyclo trial results shouldn't be discarded because it wasn't controlled.
I think the cyclo results tells nothing until we have a way to do a trial that can be relied on, and I think the toxicity of cyclo makes that unethical anyway. There were just as 'spectacular treatment effects' with the OPEN rituximab study as with cyclo and we know these were spurious. So there is every likelihood that the
cyclo results were too. Cyclo really doesn't do much to B cell activity on its own at the doses given so it is highly unlikely that it had an effect through B cells (particularly as even rituximab did nothing). Cyclo might conceivably have had a useful effect through some other means but my estimate of the likelihood is close to zero.
All I am really trying to say here is that we have learnt that for at least some people with a diagnosis of ME there can be a huge placebo effect. That is not disbelieving or gaslighting,it is a fact of life. And my impression from watching my wife receive psychotropic drugs is that they are probably even more risky than we are told.I suspect most of them made her worse and bad enough to be tube fed. I would urge people not to play around with them.
