New Data Reveal the Full Extent of STAR*D Failure

The initial study, which has been used to promote antidepressants, employed outcome switching to hide poor results.

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Psychiatrists tout the STAR*D trial as strong evidence for the use of antidepressant drugs. It was a real-world study of over 4,000 people with depression who were able to receive up to four different trials of antidepressant drugs. The STAR*D researchers reported that over the course of the study, more than two-thirds of the patients had remitted (no longer had depression).

Since the 2008 publication of the STAR*D results in the American Journal of Psychiatry (AJP), however, those researchers have been criticized for misleading the public about the true remission rates in the study.

Now, in a new study, researchers were able to obtain the patient-level data used in the STAR*D. Based on their analysis, the true remission rate—over the year-long trial—was a little more than one-third.

“In contrast to the 67% cumulative remission rate reported in AJP, the actual rate was 35.0% when using the protocol-specified HRSD,” the researchers write.

STAR*D was an open-label, real-world trial of antidepressants conducted at 41 different treatment centers. The study was meant to show outcomes after one year. There was no placebo control group with which to compare the results.

The study included 4,041 patients with major depressive disorder. They were started on the SSRI citalopram (Celexa), but if they did not respond to that drug, there were three more treatment levels, individualized for each patient. There were 11 drug combinations offered in the study. This was meant to reflect real-world practice, in which patients who don’t respond to a drug are (theoretically) given a different drug until they find something that works.

The 2010 Reanalysis

In a 2010 study, researchers H. Edmund Pigott, Allan M. Leventhal, Gregory S. Alter, and John J. Boren reanalyzed the published results of STAR*D—combining data from various tables and other data reporting—to discover that the original publication had misled the public.

The STAR*D researchers submitted a protocol before conducting the study, which outlines exactly what measures will be used and how they will be reported. In that protocol, remission on the Hamilton Rating Scale for Depression (HRSD) was listed as the primary outcome measure—the main way to tell whether the treatment was successful or not.

However, in their AJP publication of the STAR*D results, the researchers did not include the primary outcome of remission on the HRSD. They simply left this out of the publication entirely. Instead, they reported on a different measure, one that they themselves created: the Quick Inventory of Depressive Symptomatology—Self Report (QIDS-SR).

Crucially, the HRSD was delivered by a third party to ensure that the researchers were blinded to the outcomes, which guards against their biases and the placebo effect. Unlike the HRSD, though, the QIDS-SR was unblinded, meaning that researcher biases and the placebo effect likely enhanced the scores.

However, without access to the original patient-level data, it was not possible to see exactly how much this outcome switching affected the results. That’s why the new study—with its finding that only 35% counted as “remitted” on the HRSD—is so important.

In 2010, Pigott, Levantal, Alter, and Boren documented that 607 of the STAR*D had an HRSD score of less than 14 and thus were ineligible to be in the trial because they weren’t very depressed to begin with. Yet, many in this group subsequently scored as remitted during one of the four stages of active treatment, inflating the remission rates.

Moreover, for those that remitted and entered into the year-long follow-up, they would not be scored as having “relapsed” during the follow-up unless their scores rose back up to 14 or higher on the HRSD scale. Thus, patients in this group of 607 who weren’t eligible for the trial in the first place could be counted as remitted and non-relapsed at the end of one year, even though, at that point, they were worse than when they entered the study.

And finally, Pigott, Leventhal, Alter, and Boren found that the actual number of people who stayed remitted and continued to the end of the trial was dismal—108 of the 4,041 in the trial, or about 2.7%.

A huge percentage of the STAR*D participants dropped out of the trial. Almost 10% dropped out within two weeks, and over a thousand participants dropped out during their first trial of antidepressants—many of them counted as having “remitted,” despite the fact that it’s usually people who do poorly or have adverse effects that drop out of studies.

The 2018 Reanalysis

In 2018, Pigott and other researchers—led by renowned Harvard researcher in placebo studies Irving Kirsch, along with Tania B. Huedo-Medina, and Blair T. Johnson—were able to access the patient-level data. They analyzed this data, focusing on just the first antidepressant trial in STAR*D.

Kirsch, Huedo-Medina, Pigott, and Johnson juxtaposed these outcomes to comparator trials of antidepressants (studies that compare antidepressant drugs against one another, rather than against a placebo, since STAR*D did not have a placebo group).

In comparator trials, the average improvement in HRSD score is 14.8 points. In the STAR*D, it was 6.6 points.

In comparator trials, the average remission rate is 48.4%. In STAR*D, it was 25.6%.

In comparator trials, the average response rate is 65.2%. In STAR*D, it was 32.5%.

They add that the antidepressants in STAR*D performed worse than what is typically seen from a placebo group in clinical trials.

The New Reanalysis

In this context, the new reanalysis of patient-level data, which shows that the original STAR*D publication used outcome switching to double the efficacy of antidepressant drugs (from 35% to 67%), is a confirmation of the way the original study results misled the public.

The reanalysis was conducted by Pigott and Kirsch, along with Thomas Kim, Colin Xu, and Jay Amsterdam.

According to Pigott, Kim, Xu, Kirsch, and Amsterdam, the highly publicized inflated outcomes presented in the original STAR*D publication have left the public with the incorrect assumption that antidepressant drugs are effective for over 15 years. They argue that this misleading data has led to a failure to search for better interventions that could be more effective.

“Bias in the clinical literature is commonly associated with industry-funded RCTs, not publicly funded ones. Our RIAT reanalysis though documents scientific errors in this NIMH-funded study. These errors inflated STAR*D investigators’ report of positive outcomes,” they write.
“The STAR*D summary article’s claim of a 67% cumulative remission rate was published in 2006. If STAR*D’s outcomes had been reported as prespecified, its model of care would likely have faced much stronger criticism 16 years ago and fuelled a more vigorous search for evidence-based treatment alternatives,” they add.

 

 

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Pigott, H. E., Kim, T., Xu, C., Kirsch, I., & Amsterdam, J. (2023). What are the treatment remission, response and extent of improvement rates after up to four trials of antidepressant therapies in real-world depressed patients? A reanalysis of the STAR*D study’s patient-level data with fidelity to the original research protocol. BMJ Open, 0, e063095. doi:10.1136/bmjopen-2022-063095 (Link)

21 COMMENTS

  1. Did the STAR*D study used “add-on” medications?, like benzos or Z-drugs, etc. during the study? Because I remember the kitchen sink approach in a”treatment-resistant” study recently published that got around similar(!?) rates of “got better” as this reanalysis?
    How does the use of add-ons compare to the reference rates of improvement, remission and response in the “comparator” studies?
    How would that affect the intrepretation of this reanalysis?
    So, assuming the comparator studies and the STAR*D, and maybe(!?) the kitchen sink approach, are not THAT different I guess I’ll imprint in my mind, that as for depression and SSRIs you get between ONLY 50% to 40% the “benefit” in more real life-like conditions, relative to what you could expect from published RCTs.
    Assuming you reach the end of the “trial”, and the depression is “bad enough” at the beginning. Alternatively or complementarily, certainly not contradictorily, there indeed is/may be a strong placebo effect in SSRIs use, since this was “open-label”, and a strong, maybe, “kindly leave because of side effects” effect. This last one more noticeable, not less (another irony), in an open-label fashion? (am I wrong?). Like a “nocebo get better” effect?.
    Funny, a clinical psychologist over 20yrs ago told me something like that: half the people stopped taking SSRIs within 30 days of starting them because “they felt better”, despite that it takes 4 weeks for patients to actually START to “look better”, talk about patient insight beating the clinical eye!. Or was it “foresight”? Precognition?. Nah, maybe just banal nocebo lived experience, perhaps…
    His words more or less, both statements not at the same time though. And he was a smart, educated, even cultured, although aggresive and a little antisocial fellow, to my mind, that described himself as a “people’s person”, another irony. But yeah, conceding, he didn’t call himself a people’s pleaser. My cynic inside made me write this: “How could he? Honestly?”.
    Am I wrong?, surely I am, somehow, somewhere with something. And by analogy or extension, the kitchen sink approach “got better” rate would be less than half the around 25% that I think I missremember?.
    Was there any correlation between the leaving rate and the “severity” of depression at the start of the trail or during it? like because side effects or drug switching?.
    Could that explain the “got better” rate recently published, also in some BMJ mag, that suggested that MOST of the SSRI “got better” rates occur on the top raters in the severity scales of depression? Like, they have no better choice that to stick with the treatment and “wait” for the “got better” either way kicks in?. Weren’t these last rates also around the same 30% range?.
    So these “new” results could or would(?!) bring down the clinicaly “unnoticeable” depression improvement with SSRI treament above (or was it below?!) the mythical expert consensus 3 points in depression scale from RCTs to less than half than it was before? Or was it 2 points? Or was it 7 points?
    I mean, explain, me trying to make a collage, not a puzzle since the pieces seem no to fit, that is understandable out of so much discordant info…
    And from other reviews here in MIA, one could get over 400% the side effects and risks, relative to what is published, originally, in the RCTs, if I’m remebering correctly. What a pickle and ordeal from trials, clinical ones that is. Even reading about them sounds excruciating, I imagine going through at least one, medication or trail, either or both?.
    Note to self, I got to start taking notes, and I have a first good one…

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    • Yeah. Back in med school, apparently after ONLY a written test I was serially, informally and covertly labeled: schizophrenic, preschizophrenic, borderline, and even Hitler-like. Just from a written test that was not the “official” 300 item questionaire used back then, and certainly not done alone, in an office, with a single trained and qualified pro in front of you. But it did include a Bender test that apparently wasn’t mine. It was like … forged.
      Several yearZ later this psychologist told me in his “office” that I had the mind of a “serial killer”, not his exact words, but close enough. His exact words where: “Cold blooded killer”. Red faced, puffy cheeks, bending forward, upper teeth showing. Talk about explosive therapy. I might be confabulating that even his fists were clenched….
      Apparently, based, mostly I figured, on “comments” from my then “schoolmates”, maybe even some “professors”. They actually mobbed me not “just” bully me, but he obviously never got that, the mobbing, at least not from me. And I imagine that he thought, I fantasize, that since “I didn’t whine”, that qualified me as “reality test failurer”. Fortunately, before that a psychiatrist did mention ONLY to him, that I had the profile of a persecuted refugee, geez, I wondered why?, which led, I imagine to formalize a “depression” diagnosis on me. To me she said that I was actually not bipolar, “no chance in hell”, she wrote, I hope…
      YearsZ laters, two other professionals ran again the rooster of diagnoses: schizophrenic, preschizophrenic, borderline. But not the psychopath one, and since I survived at least FOUR antidepressants without becoming manic, I guess neither the bipolar one, at this time, maybe when I was a child and no one told me? I did have a bad case of anomia back then, who knows?!. I still do, on and off, geography is not my stronger suit…
      Odd, I guess that part of my personality traits, the psychopatic ones, “permanent” as defined, closely, in the DSMs, didn’t survive the cuasipersecution. Egoreductive informal group therapy might have done THAT trick…
      YearZ laters, same thing. Only then, I was downgraded to: “just”, plain, simple paranoid, after being labeled by a paranormality believer clinical psychologist as some type of “schizo” personality type, like just pick one, any, it’s an SPECTRUM, more or less her words. She did recomend I read a book about REAL spiritual? angels and demons to FIGHT against the EVIL, I suppose in my life or around me. Never cared much for the paranormal myself. I’ve always been on the skepticamp, since a young kid, really. But I do respect and enjoy talking and sharing with people who do believe in that, some of the time, with some people.
      Funny, my only delusion was actually “self fulfilled” said one of my “medical” (uughh!) kidnappers, in training, not a qualified fellow. I told him, like many pros when they say to me something like that: I am neither smart enough nor diabolical enough to make people do whatever I want. I never told them: “Geez, talk about YOUR delussions of MY grandeur!”. But I did point into that direction, with the predictably bad attitude of someone who just got “served” by a “crazy” person. Or more precisely “another” crazy person.
      And I added to the “last diagnosis” about “my” delusion: “You know, that’s not what I believe!, that’s actually what people said to me, including one Medical Director at THE biggest private hospital in a relatively big city, when I was working there, because bad things happened and his inmediate underling was involved in apparent “criminality”, inside and outside the hospital in which he was THE medical director. And the only “crazy person” to actually write a partial complaint about it was actually yours truly. And he did mention that he was unsure, the medical director, if there were ANY others like his underling, and questioned why I didn’t include his underling’s name in my complaint, to which I answered: “Because he is your underling and you know better than I do what he’s suspect of doing”. And actually, without me asking for him to provide such independent knowledge or point of view. He did mentioned that he ‘asked around’ outside the hospital, even in my med school, and got that ‘impression'”, among other things. So not even, to my mind, “my delusion”, but HIS or an independent corroboration without being prompted by me, if at ever I had THAT delusion. Obscure, but…
      Some shameless pro might think, even quip, THAT was actually another reality testing done outside the “office”, but he was, to my mind, more concerned about lawsuits or journalists, and a few months after that, casually in the street he did asked if “someone” stopped mobbing me. Not his exact words, but close enough. He even wished me luck or something to that effect. So, sounds legit comments to me from this fellow…
      And in all of that, when I asked for the pros to put each criteria that I, in their opinion, fulfilled for each diagnosis, got nothing, just ONLY one in each, some heavy hand waving, red herring and ad hominem, and ALWAYS a refusal overt or covert to put it in writing for me to keep and read.
      But, I did got the impression, that at least all of these pros, actually diagnosed me with what THEY had!. Not that I believe in the psych labels, but if I did, I probably would reach THAT conclusion more than 80% of the time, in my limited “sample”. But I fear, that would be another delusion…
      I vote VERY persecutable personality disorder and mirror personality disorder to be added to the DSM-VR or the DSM-VI. 🙂
      Oddly enough, some other colleague did mention the last one, since aparently I do behave similarly to my current interlocutor, in serial fashion. Which I guess makes me sympathetic although of an obnoxious kind to some “pros”, hence the border/bipolar label on me, I fantasize, I look unstable AND annoying somehow. And I guess being sympathetic is actually a real SPECTRUM of the non-paranormal non-dsm kind.
      The medical director and this colleague did mention that to some people I actually “show them” what they dislike, go figure what that could be, sounds more like a gasslightning comment to me, but might be actually true. And always there has been the omnipresent profit motive in my serialized diagnostic gamut, so…

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      • Could be that these “brilliant” shrinks paid no attention to your physical condition. Pernicious anemia is treated with B12, which has antidepressant (and sometimes antipsychotic) properties, while depression is common in the anemic, for obvious reasons. Are you under the care of diagnostic morons?

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        • 🙂 You can’t be, by definition under the care of diagnostic morons… Care and moron in the derogative don’t belong in the same sentence, by definition.
          And yeah, at least 2 genetic contidions and at least one systemic disease, not condition, disorder nor spectrum, that don’t bode well, let alone together, never formally diagnosed, but easily confused, I have documentary evidence, not just opinions. Not vitamin deficiency and certainly not anemia, at least not a clinical one as opposed to a “laboratory” one…
          But, in full disclosure, anyone could have missed those, not after obvious signs, but as symptoms, anyone can miss those. Let alone if the diagnostic “savants” never asked, or never put it in writing.
          Hence the relevance to my mind and my experience of not using cohersion but humility, kindness, knowledge and understanding when dealing with living things, not just humans.
          And not just “shrinks”, survivors turned “activists” do try to diagnose people on the street, in their house, in their school and in their work like the law, their knowledge and qualifications allowed them such. Which is not the case, specially if there is not informed consent for each and every one of the painfull and harmfull diagnostic attempts on ANY individual. Just asking: “Are you o’right?”. “Do you need help?” with a “clinical” eye is bound to be hurtfull, I’ve seen it, I’ve been there. The difference to my mind is: Are you diagnosing? or caring?. Are you being clinical?, particularly without knowledge or qualifications, let alone in places the law does not grant you specific authority to do so, or are you “just” being human and/or decent?.
          And since NO ONE can’t know before hand if a PARTICULAR question, even a glance, hurts, you can not glance, ask or “diagnose” ANYONE before asking each and everytime before doing so, since YOU don’t know if its going to hurt. That’s informed consent.
          Not picking on you or your comment, just laying the way I see it, and why psychology, psychiatry and “activists”, regardless of their expertise, can’t do any diagnosis or even ask a question, since they can’t before hand know what is hurtfull and what is not, in a particular individual. Just saying 99% of the “people” is not bothered by it, is not enough, it has to be individualized.
          Two clinical psychologist admitted to me that THEY could not ask for informed consent before asking hurtfull questions. To which I replied somehow: Then you should not ask ANYTHING. Imagine how they reacted and that sadly, kept doing it.
          The psychiatrists invoked the fifth..
          Thanks for your comment, I, can gladly write, am not hurt, offended, minimized by your concern. On the contrary. Thanks.
          And, blank consents, like in therapeutic contracts, have no meaning. I do suspect some ex-partner forged my signature on one of those babys and a public notary validated another from some cuasi-criminal lawyer when I was just looking to validate my signature on an unrelated matter. On the last one I was even threatened to sign a recipt on a document that I don’t know what it is INSIDE the office of the public notary…
          And you might think I was just lame…
          But, I did got the to the highest authority that supervises the FEDERAL JUDICIARY with a formal complaint, and in turn, as I understand from NEXOS magazine, in Mexico, was turned to the District Atourney, federal I imagine, because of acts against the law commited in one of MY cases by at least one, then appeals federal court judge. Which I understand is highly unusual, most judges, appeal judges and supreme court justices rarely if at all, turn cases from a complaint into the district atourney, it is said in some Nexos magazine issue on that. So my complaint, must have included some “evidence” of the undeniable kind.
          So, I did have reason to fear for my life.
          And, one may think having videos, photograhps, “hard evidence” of “fabrication” from AN authority would grant you an “acceptance” of a lawsuit or complaint against an authority. Not the case, I did have, and still do have that, and it never “prospered”.
          One might thing a human rights comission might do something about it. As Michio would have said: “Not so fast”. My human rights comission file, the official published one contains a narritive, as a quote, that I never wrote. I do have the original and the certified copy for comparison. I am skeptic that that formal, to my mind, offense, as in fabrication, is going to be prosecuted, given my past, limitedly stated, experience.
          🙂

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        • Not giving medical, legal, or otherwise advice or analysis.
          When I said formalize was like they made up their mind about me being depressed. As far as I’ve been told, I’ve never met the threshold to be diagnosed as clinically depressed. On the short/brief screening test it was just above the score, but subsequently it never met the clinical diagnosis, as far as I was told, never. The SSRI treatment was “empirical” not diagnosis based.
          I had never had hallucionations nor delusions, so no psychosis, at best/worst deliroid ideas. Negative hallucinations are an invalid construct that can’t be experimental because of moral concerns (my analysis), but the first part is published. Dream related hallucinations are not part of psychosis but of the living human dreaming state, as hopefully and optimistically Albert Szent-GyĂśrgyi would have said. Tinitus is not an hallucination, and so forth. What other kind of hallucinations are left?
          Hearing voices “inside” your head, are not hallucinations, hallucinations are heard outside your head. Just to clarify what I learned on the semiology of neurological signs and symptoms.
          So, neither of those considerations, depression, psychosis, personality disorder fits. Clinically, on psychological or psychiatric complaints, in my case up to now, did not even merit a laboratory test, they required and still do intervention by the judiciary, not a medical prescription. Let alone a lab test.
          My symptoms were in whole understandable, as that: complaints, as part of my human condition in my then and now circumstances. That was my point. False positives do happen in any laboratory or clinical test, therefore they should be done only when the apriori probability of being sick overrides the false positive rates, AND there is actually something SAFE and USEFULL to do about a positive test.
          Blank screening tests require a very high confidence to be used on undiagnosed/unfiltered population AND a treatment that actually brings more benefit that harm in an individual DIAGNOSED because of a lab test, not because of a clinical exam and a medical history. Those are TWO very different clinical situations that require very different management.
          But I did got assaulted and forcibly drugged, as I figured out decades later, by a female school mate that apparently at least had auditory hallucinations and severe negative symtoms, probably because of her delusions and with the help of a psychiatry resident that, as far as I know, never consulted with her hospital to drug me, like in date rape, literally, and leave me a scar evident in radiographies.
          So, if a diagnosis, even a laboratory one was warranted in my case would have been: criminal administration of a depot neuroleptic by a still psychotic female under supervised treatment complicit with a criminal psychiatry resident, that predictably never wrote it in my medical records. But my then psychologist, my vascular surgeon, two later psychiatrists never told me, but oddly enough did ask for a radiography to check for the scar. The vascular surgeon even touch it “fresh” and never told me, and certainly never informed the autorities.
          As for the two psychiatrist never did either, they are the ones that asked for the radiography and never told me why, they said I had to trust them, don’t ask questions, and just do it at a particular place, because apparently, if I were to go ANYWHERE else, my radiolography would have been replaced with one from some other patient. It happened to me on another test, I have evidence they switch those things at least in my case, I nailed the female radiologist that switched one on me. I have that evidence to back me up. The bones evolve over time, but don’t just morph into someone else.
          On top of that how do I know that for more or less sure? Because I have been ORDERED to not deliver radiographies with such scars to patients, but to separate them and turn them to a “special” person, not unlike my then psychotic schoolmate but with a more obvious psychopathic personality, with an MD in charge of training aspiring specialists in a top public medical center in my country. I have a witness for the request, will he testify?, dunno. He’s the one who asked me on behalf of the psychopathic MD!. And the psychopatic MD did came complaining obscurely, talking to the wall, literally, about “someone” not following her indirect instructions. Of course NEVER in writing.
          They were all complicit, and I have the scar and the physical exam of the TOP vascular surgeon to prove it, from a TOP university in the US, nonetheless, they publish a LOT of books on the medical field, like a LOT. With a witness the vascular surgeon brought into the examining room for some reason I ignore.
          Enough said for me on that I think.

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    • Completely agree.

      I was diagnosed with bipolar II at 17, was swapped to borderline (which I vehemently resisted due to the amount of stigma I was facing from all sorts of clinicians), and then back to bipolar II.

      Fifteen years, 31 different psychotropic medications, and two extremely long courses of ECT later, and I finally found the language and strength to describe my observations/frustrations to psychiatrists who were willing to listen, and even agreed that the language of the borderline diagnosis is stigmatizing and invalidating in and of itself. Now people are coming around to what in my heart I always knew was the root issue: Complex PTSD.

      Every time a borderline diagnosis was given to me, it was always with a sense of futility, dismissal, invalidation, judgment, and in the case of two psychiatrists, a visible sneer.

      If their prescribed therapies or treatments don’t work, I’m resisting or sabotaging my treatment. If the coping skills to manage the unbearable emotional-agony prove ineffective, I’m manipulative and attention seeking. If I have a legitimate concern, I’m being combative. What simplistic, “black-and-white” thinking on their part.

      People labeled borderline do not like being in the ridiculous emotional turmoil they experience. No one would. People with borderline are people. People are more complex than the simple, surface level reasoning the mental health community has provided for a phenomena they are too lazy, or uncreative to accurately describe or treat.

      I mean, god forbid a clinician’s ego gets bruised! Most are so obsessed with being right and retaining their power/status, that they disdain being truly helpful. They’d rather us suffer, than their theory prove false.

      (In case anyone is curious, psychedelic assisted psychotherapy helped me immensely, although I’m still not quite where I want to be yet. I’m going to try schema therapy next. At least I never have to take another blasted psych med again!)

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  2. Oh! Oh! I forgot to mention that during the red faced psychologist part of my life, a professor was really insistent with the Mr Ripley character portrayed by Matt Damon. But I guess that would be part of my diagnosticable self referential thoughts, not a TOOL of mobbing and gasslightning…

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      • This, to me, quasi-law of thirds keeps appearing, again and again, even in the placebo/nocebo effects if I am not misremembering. Like there is not a biological thing, but a STATISTICAL thing that from a third gives you the 95% conffidence interval.
        Like a math thingy that just won’t go away precisely because it is related to the p<0.05, just by luck, by random if you try long enough. Like getting 1/6 out of a fair dice..
        Taking into account that these are experiments on the living, not on dice.
        Dunno, my knowledge of stats is just lacking.
        I'm not getting esoteric, just can't miss the apparent to me, maybe errouneously pattern.

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      • But there is an over 80% spontaneous remission reported on a “self limited” “spontaneously self remitting condition”, like depression “used” to be considered and evidence NOW suggests somehow is for the MOST part the case, without medication, I assume.

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      • And the percentages do have the issue of the confidence interval, like in between 10% and 90%, not just the “mean” of the confidence interval, lame as that sounds, worse when comparing two populations, pressumed different, and not noticing that 90% of indivuals in both of them, fall within the 95% interval of BOTH, which by just looking at the dot graphs tells you they are the SAME, before and after threatment or follow up. Not sure it’s the case in psychiatry but it is and was the case in some studies that I read years ago…
        Which, as far as I know can’t also be individualized since that is for the most part reported as an aggregate, or without the relevant variables, specially in psychiatry where there is no physiopathology, since not knowing what scientifically speaking depression is, the variables cannot be established. Is weigh, height, skin color, occupation, altitude, barometric pressure, diet or genes a relevant variable?. Is the easyness or availability to be diagnosed THE relevant variable?. Which ones and with which weight? A fishing trip to the multiparametric regression to my mind won’t do the trick since it is an epistemic issue, not an experimental one.
        Hidden variables in physics are not just being ruled out completely, so. The mythical wormhole is neither confirmed nor denied experimentaly, and string theory lasted more than 30yrs, as far as I remember. And that is physics not pseudoscience.
        Hardhsip is a relevant variable, but how do you meassure that? whith another unvalidated set of variables? With an unvalidated questionaire? With a formulation? With an ‘opinion’?. Uuuugh!.
        Just being facetious, hardhsip IS the only relevant variable to my mind, not “trauma”, not giving any advice though…

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  3. And I think I, at least, have a conspiratorial codeDavincian “theory” of how this mythical, to me 30%, keeps showing up:
    I remembered that around 2 decades ago I read in Scientific American a report on the research of an MD, PhD, researcher and published writer about the lack of published studies that showed no effect of SSRIs in depresion, he even showed a graph that I remember showed a missing third of a bell shaped curve. Findings that as far as I remeber, are published in his book “Bad Pharma”.
    So the 30% starts, being conspiranoic, with the removal of the data points, be that individual patients or published studies, that shows not only no improvement, but among those data points WORSENING by the intervention, which in this case is medication.
    So that the published record shows ONLY those data points that by randonmess, chance, regression to the mean, etc., anything but a positive CAUSAL effect on the depression metrics can be used to prove an statistical “forged truth” of efectiveness/utility.
    Then you are left with the 60 to 70/80% of people or studies that as stated can be used to justify a causal role in improvement of depression.
    There was even a TED youtube talk about it, there is a book, and there is the Scientific American article. And I think a lot, lot more now. Then the increase in self-harm risk wasn’t very known, despite very famous lawsuits and media articles.
    I thought that was the end of SSRIs back then, because I thought to myself: What kind of physician would keep prescribing a GROUP of medications based on publications by an industry that mislead the medical and scientific community?. Wouldn’t that have broken the implicit trust that what you read is at least reliable? let alone truthfull?

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  4. https://www.spokesman.com/stories/1995/dec/16/pied-piper-of-prozac-defends-use-of-drug-state/#:~:text=News%20%3E%20Spokane-,’Pied%20Piper%20Of%20Prozac’%20Defends%20Use%20Of%20Drug%20State%20Board,Determine%20If%20Therapist%20Mentally%20Impaired&text=A%20Wenatchee%20psychologist%20known%20as,mentally%20unfit%20for%20his%20work.

    Does anyone know about this town in Washington state, Wenatchee, where a large percentage of the population was prescribed Prozac? Apparently there was a clinical psychologist there who got prescribers to put his patients on Prozac and then later on maybe he lost his license?

    If it’s true that a lot of people in this town were put on Prozac, I wonder if there were any follow-up studies. I saw one thing that said that the rates of crime went up after this happened.

    https://www.freedommag.org/english/vol33i1/page05.htm

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