Antidepressant fraud over antidepressant ineffectiveness

It's long been known that many antidepressants seem to be little better than placebo for major depression.

The typical answer from the psychiatric world, if not from every individual psychiatrist, has been "give it a little longer." (To the degree that anti-Ds, whether old tricyclics, newer SSRIs or newer yet SNRIs, do seem to have any direct physical effects, stimulating synapse and/or brain cell growth does take several weeks.)

If that still doesn't work, then the psych world answer is: "Let's try another." Lexapro instead of Celexa. An SNRI instead of any SSRI. Etc., etc.

What if the primary research cornerstone that still upholds the antidepressant world is itself based on Big Pharma research fraud? What if the mainstream media hasn't picked up on that yet, because it largely follows psych world PR?

That's exactly the contention of psychiatrist Bruce Levine, a regular Counterpunch contributor. Levine says this isn't totally new, either; only 4 years after the 2006 STAR*D study, the issue of publication bias in general, though not actual research fraud or the spirit thereof, was raised about anti-D efficacy.

Yes, research fraud or the spirit thereof, as STAR*D investigators didn't disclose their pharmaceutical ties. And, the fraud that's documented is clear and easy to see. Dropping people out of results although part of a test group, for example, if they dropped themselves out of the research before complete. (These people made up almost one-quarter of the test cohort.)

What if they had?

Levine links to a piece from the Mad in America site that covers this in more detail. That said, unless I'm hitting a paywall, it ends with this as a rhetorical question.

And, Levine himself shoots down the rhetorical alternatives. He says, for example, that ketamine is as overhyped as SSRIs.

(T)he research on ketamine as an antidepressant is worse than disappointing.

Given its clear side effects, it's hard to see how it could not have a placebo effect as big as SSRIs.

He also notes that, even if the "chemical imbalance" theory of depression isn't accepted today, if STAR*D's truth had been told early on, this idea never would have taken off. 

Among issues involved, to the degree that anti-Ds do appear to change neurons, we don't know how they change them, if they change only brain neurons, what changes may affect mental health and more. Re the demise of the chemical imbalance theory, all brain neurons have multiple receptors for each of the main neurotransmitters. We don't know which ones might be affected by depression, anxiety, etc., and how anti-Ds may or may not affect that.

Levine doesn't discuss electromagnetic interventions, such as old electroshock or more modern transcranial magnetic stimulation. He does say he has his own antidepressant:

I do have my own personal antidepressant, which is Albert Camus’s essay The Myth of Sisyphus. Camus argues that the realization of the absurd does not justify suicide, and instead compels rebellion that can be vitalizing. Camus concludes, “The struggle itself towards the heights is enough to fill a man’s heart. One must imagine Sisyphus happy.”

And, we shouldn't take that as a joke. Without going fully Thomas Szasz, we need to look more at the social psychology aspects of depression. I say that because I think things like schizophrenia are not totally socialized psychology, and so, don't totally go down the road of Szasz.

John Horgan, who's long been critical of the Big Pharma world on mental health, had this to say after I tweeted him Levine's link:

This is a huge medical scandal, which should be much more widely disseminated and discussed. https://t.co/BogjK3WAl8

— John Horgan (@Horganism) January 18, 2024

He's right. And, of course, this coming in the wake of COVID and conspiracy theories over mRNA vaccines overshadowing people like me who see their relatively low effectiveness, and also see a Biden Administration refusing to use federal power to deal with copyright issues, and you have additional problems both social and political.

Side note: The Twitter exchange has drawn at least one COVID anti-mRNA vaxxer, if not more than that. But, said person has been told the truth, has been seen to retweet racism from VDare and other stupidity, and the conversation has been ended. 

As for that person and others? The real scandal, not just over mRNA vaxxes, but to some degree, all COVID vaccines, is that neither Trump nor Biden, based on federal whipping of "Operation Warp Speed," that neither one exercised federal patent rights.

==

Personal note: I have been on antidepressants before for the flip side of depression, acute anxiety. They seemed to have work, but how much of that was placebo effect? How much of it was me "aging out" of the anxiety problem? And, I have had the side effects.

Deconstructing Sarah Fay

Cliches become well-used before they get known as clichéd for good reason: They express near-universal truths, to venture into the land of clichés. And, the best of them never become hackneyed.

With that? 

"Trying to have one's cake and eat it too" is the best I can think of on Sarah Fay's attacks on the DSM, the Diagnostic and Statistical Manual of Mental Disorders, the "bible" of counseling psychology and psychiatry, in her books "Pathologized" and "Cured." Hers is not by any means the first such attack; indeed, as noted on my Goodreads review of "Pathologized," which expanded to cover both books when I noted, via her website, that "Cured" is being published for free reading (in part?) in Victorian-type serialization on Substack installments, (See near the end for specific takes on specific chapters.) I long ago wrote a long, detailed blog post about Asperger's being "schizold disorder of childhood" until DSM-IV.

Pathological: The True Story of Six Misdiagnoses by Sarah Fay
My rating: 2 of 5 stars

This is kind of a hard book to rate. Or, it was, until I hit Fay's website and became more agog at what I read.

I will spell out in more detail, wrapping up with heading back to selected portions of the review, how it earned that 2-star rating, including warnings to readers of this book or her in-progress sequel, "Cured."

Hers is also not the only attack on the pharmaceutical industry in general and its psychotropic wing in particular.

That said, despite some Overton window shifting in her referencing a "recovery model" of mental illness, she seems to not only accept the need for such medications for herself, but to accept such need willingly, not grudgingly.

Just one problem. Such medications are prescribed based on a mental illness diagnosis. Such diagnoses are based on mental illnesses mentioned in the DSM, however imperfect it may be. To want such medications without accepting an accompanying diagnosis? More specifically, to want a doctor to prescribe without offering an accompanying diagnosis? That is essentially asking a doctor to commit medical malpractice.

If this is not the impression you intended? You've got a Ph.D. in English, creative writing or similar. I suggest you contact yourself or your editor if that's not the impression you planned. But, you can't have your cake and eat it.

Fay's story has other issues, some about her story, and some about her understanding of psychological counseling. The calls of her, and other people, for patient centered counseling?

Has she, and have they, never heard of Carl Rogers and his client-centered approach? It's like she (and others whose shoulders she stands on) are reinventing the fucking wheel. "Pathologized" never mentions his name, nor do the parts of "Cured" already available for reading. I would have checked the anti-DSM website of hers listed on the dust cover, but? It's expired. (Also interesting.) She loses claims to credibility right there. It's not entirely her fault; the therapy world today seems to be "meds here, cognitive behavioral therapy there." Other counseling modalities (she does mention dialectical behavioral therapy once) get ignored. Group therapy, gestalt, etc? Not mentioned. The broader humanistic psychology (which does not generally include gestalt) also ignored. Not all elements of humanistic psychology work well with more serious mental illness, even when medications come first. Nonetheless, for neurotic-level depression, alone or with hypomania, neurotic-level anxiety and other issues? It can be very good. 

As for patient involvement in general? Did you really not get involved in dialogue about your medications for 20 years or whatever? That may be something symptomatic of women's treatment in mental health. If it is, you really didn't discuss it, even as a couple of Goodreads reviewers noted this, race, etc., have long been "problematic." On the other hand, you mention at least one female psych and other female counselors. If not asking questions for 20 years reflects other obsequiousness to authority? That's not a mental health problem but it may be a personal development one.

Otherwise, what the new "recovery model" focuses on in one way is also just like the old humanistic psychology, and can be summed up in one word, a word I nowhere see in Fay's writing: "acceptance." It's that simple.

Then, there was her reply to me on Substack. She said "Cured" "isn't an advice book, it's a memoir." The two aren't mutually exclusive. "Pathologized" is a memoir, but it has an epilogue, which most memoirs do not, and that epilogue is very much an advice book.

I also found interesting that the circle wasn't closed in "Pathologized." Fay, if not full-on anorexic, had some sort of eating disorder as an adolescent, during the run-up and through her parents' divorce. Relations as an adult seem somewhat strained with her mom at times and more so with her dad before in the end of the book, she seems to indicate all is hunky-dory with both. But, she never talks, even in generalities, about how that happened, given that the relationship was clearly "distanced" per later parts of the book. And, at the same time, after her parents split, during high school, she bounced back and forth between them. Color me skeptical. She also talks about the "murky pit" already in the first chapter. That may not quite be Churchill's "black dog," but it sure sounds similar. So, two of the six misdiagnoses she alleges don't seem to be misdiagnoses.

That's even more true when one reads her essay "On Suicidal Ideation". "Interestingly" (that's scare quotes, Sarah) much of its material did NOT make it into "Pathologized." That includes not only details of the frequency of her ideation, but that she had a less hateful take on the DSM. And, that's not ancient history. It's 2019, and "Pathologized" went to press in 2022 and was surely in writing a full year or more before that.

And, while not a counselor myself, she strikes me as a "highly sensitive person," not just in the sense of the book of that name, but more. She seems to have a highly developed sense of interoception, which in turn then would influence her high emotional sensitivity. None of that is either good or bad; it simply is. That said, it should be noted that interoception that is off the norm is associated with many mental illnesses.

And, with that, on to extracts from my Goodreads review.

Near the end of the book, Fay does slightly nuance her diatribe against the DSM, and against mental health diagnoses.

I give you the last two sentences of the Epilogue:

Before you accept a DSM diagnosis, pause. That doesn't mean you don't seek treatment or take medication or ultimately decide that having a diagnosis, no matter how tenuous (at least for now), serves you, but you do so knowing the truth.

Sadly, especially given my further digging around, it's too bad those words weren't in the first two sentences of the Prologue or Introduction.

That said, she's more close to right on the DSM, and the DSM's evolution, than many 3-star reviewers give her credit for. On the other hand, that has to be seen in light of her suicidal ideation essay, which frankly raises questions of "why the shift."

Beyond the DSM, although she doesn't go into it a lot, she's right as rain, including her own experience, of too many doctors still peddling too many benzos for anxiety. Or antipsychotics. Anti-depressants are another option (especially if used in low doses with talk therapy).

She doesn't square the circle with her opening chapter. Whether she had full-blown anorexia or not, she had some sort of eating disorder that appears to have been in part a reaction to her parents' divorce. And, while she says she's got a good relationship with her dad at the end of the book, she never talks, even in generalities, about how that happened, given that the relationship was clearly "distanced" per later parts of the book. And, at the same time, after her parents split, during high school, she bounced back and forth between them. She also refers to the "murky pit" in the opening chapter, which sounds like depression to me. And, wanting to stay on an SSRI, plus the suicidal ideation, would certainly point to that.

So, that would mean that a minimum of two of her six diagnoses weren't wrong. They may have been partial, or incomplete, but they weren't wrong. That's even more true when one reads her essay "On Suicidal Ideation." "Interestingly" (that's scare quotes, Sarah) much of its material did NOT make it into "Pathologized," though the essay is referenced.

Now, more of a review of "Cured."

And, guess what, Sarah? Your diatribe against group therapy lost you another star, and gets a "recommend against further reading" as part of this review. (In a reply to me, she claimed she wasn't "dissing" group therapy; I differ, without begging.) In the words of scientific skepticism, you've now clearly ventured into "n=1" territory. And, you could be contributing to someone else's mental harm, not cure. Also, her chapter on recovery models of therapy comes off as glib:

Psychiatric “symptoms” like depression and lack of interest and anxiety and ruminations are part of the human condition—even psychosis. (I used to think psychosis was different but as someone I know who hears voices explained, “Ever had a song stuck in your head? That’s not the same, but it gives you an idea.”)

The chapter after the one dissing group therapy has two issues. First, "Staying on the Course" is largely a recycle plus some expansion from this book. And, she talks about Patricia Deegan being "healed" from schizophrenia. Deegan talks about "recovered," but I'm not sure she would use the word "healed." She uses the word "heal" for herself in Chapter 9, and it again seems clear that this is NOT "cure" as in the Latin root meaning "care," as she says in this book, but ... "cure."

And, Fay undercuts herself on this:

As she healed from schizophrenia, Deegan developed her own personal medicine: “Medications were just one tool in an entire set of recovery tools I slowly pulled together for myself. I built my recovery toolkit over time, intuitively, and without even having heard the word ‘recovery.’”

Time after time, it's shape-shifting from her on the issue of medications. Or? Whether better or worse, the political phrase: Overton window shifting. She'll imply or insinuate that recovery models of mental illness somehow move beyond medications .... until there they are! And, why are they there? Because of a diagnosis.

What does Fay want from her movement, anyway? If it's to be "more than a label," I think she's tilting at windmills. I don't think the majority of mental health patients, and certainly not the majority of less severe ones, identify themselves as a label. And, if she really accepted much of her psychs' advice passively for years? See above, about humanistic and client-centered therapy. I am halfway dumbfounded at this.

As for labels, and "healing"? In both schizophrenia, and in chronic depression, and in both sides of bipolar, etc., symptoms can flare up and die down. That doesn't mean the underlying condition has gone away. Happens in some physical ailments, too, like multiple sclerosis, and nobody but a sicko or a self-delusional person would talk about being "healed" from MS.

If a mix of relabeling and refocusing helps Sarah Fay, more power to her. But, this isn't magic. Nor, as I risk moving from skepticism to cynicism, is this about being a "brand." Stopping short of cynicism, there's intellectual dishonesty toward the public, and maybe toward herself, in not describing the "shift" between her state of mind at the time of the suicidal ideation essay and the start of writing "Pathologized" two years later. 

My guess on that, again at the risk of moving beyond skepticism to cynicism, or at least as being perceived as doing such? I think that some time in that two-year gap she became converted to the "recovery model" of mental illness and mental health and then became an evangelist. And, I use "converted" and "evangelist" quite deliberately. (Sidebar: I don't like the descriptor "recovery model" as it sounds too much like addiction and sobriety, where recovery generally means something quite different. It may be riffing on AA's "daily reprieve" statement, but still, beyond that, there's not a lot of parallels in the details. Sidebar 2: I could have riffed further on conversion into conversion disorder ...)

And, given that both her books are advice books as well as memoirs, and knowing there are better, more scientifically grounded, yet still personally focused, critiques of the DSM, I write this in fear that she could, with some of what she says, be a danger to others as well as being some degree of hypocrite, as I see it. On the danger part? I, along with a couple of reviewers who specifically mentioned this, wonder if some readers didn't get halfway through "Pathologized" and think they could just toss their pills. Or, per "Cured," pills or no, people thinking that schizophrenia can be cured.

==

Side note: The punctuation part of the book, trying to riff that into the different diagnoses, seemed forced. That said, it perhaps emphasizes that the rest of the book is split, per the "splitting" that Fay talks about in herself but never describes in detail (lest she get a dissociative identity disorder diagnosis?) between memoir that could have been better yet if more fleshed out, and the lurking anti-DSM screed.

View all my reviews

#Anxiety — an inside story

My Age of Anxiety: Fear, Hope, Dread, and the Search for Peace of Mind by Scott Stossel

My rating: 5 of 5 stars


A very good, and somewhat sad, and definitely sympathetic read here.

I had seen the excerpt from this book in a recent issue of The Atlantic, where Stossel is the editor, so this jumped off the shelves when I spotted it at the library.

Stossel mixes biography with scientific research on anxiety to tell us what we seem to know pretty well, what we may know, and what we still really don't know, about anxiety.

As Stossel and others know, and as he documents well in the biography part, is that a tendency to anxiety seems inherited. But, is it? He mentions a bit about epigenetics, the "tags" that can control when, how and for how long genes are activated (that's oversimplifying) and how anxiety is one of the big topics in epigenetics research. He also mentions psychodynamics, and the idea of how anxious children may learn to be anxious from anxious parenting, and thus pass that on. Meanwhile, he notes that starting with the wonder, in the 1950s, of the first drug that seemed to help depression, then others for anxiety, neuroscientists have promoted happier living through better chemistry.

This plays out in Stossel's search for help, with a "Dr. Stanford" telling him he just needs to tweak, or up, his meds, while "Dr. Harvard" says he needs to discuss his family, his personal life, and specific anxiety situations, including some existential ones.

Stossel hints they're both partially right, and that as a generally non-confrontational sufferer of anxiety, he can't tell them that neither is fully right.

Stossel, whose one grandfather was a dean at Harvard, started seeing a child psychiatrist in elementary school. That same grandfather had multiple institutionalizations later in life and eventually had to leave Harvard. His wife committed suicide. That's on his dad's side. Similar, albeit somewhat lesser, "strains" of anxiety run in his mom's family.

So, Stossel knows anxiety is real, even crippling.

His own story included gulping both Xanax and booze before flying and before giving public speeches. He admits on the latter that it's a fine issue, trying to find the sweet spot between being halfway numbed out on his anxiety and slurring his words. He also admits he knows he's playing with addiction/alcoholism fire.

Stossel also notes that he stand on the shoulders of giants -- previous literary giant sufferers of anxiety, and tells bits of some of their stories in this book as well.

I'm with Stossel in the general idea that, sadly, we don't have a complete handle on the causes of anxiety yet, only that they're complex, and the problem itself is still only roughly defined — general anxiety disorder, and its DSM definition, overlap a fair degree with major depressive disorder. I'm also with him that the "one neurotransmitter, one solution" idea of many neuroscientists and Big Pharma is way, way, way too reductive. Given that the "big three" of dopamine, norepinephrine, and serotonin all have multiple different receptor sites on neurons, and we don't know which ones antidepressants and anxiolytics affect, and we don't know what others of the roughly 100 neurotransmitters also may or may not affect anxiety or depression, this approach is reductionistic indeed.


View all my reviews

#PeterKramer says: Listen more to Prozac

In an extensive New York Times op-ed, psychiatrist Peter Kramer, well-known as the author of "Listening to Prozac," says we should take those recent studies that claim, especially for mild to moderate depression, that antidepressants are little better than placebos, with a fair-sized grain of salt.

About that claim, he says:

This supposition is worrisome. Antidepressants work — ordinarily well, on a par with other medications doctors prescribe. Yes, certain researchers have questioned their efficacy in particular areas — sometimes, I believe, on the basis of shaky data. And yet, the notion that they aren’t effective in general is influencing treatment.

Kramer's argument is basically this, as I understand it:
1. Because we still don't have exact description for what depression is, the so-called "placebo response" may be confounded by imprecision in knowing who had depression in the first place and whether they have "recovered" or not;
2. Related to that, problems of recruitment of trial volunteers.

Of that second issue, he says:

The problem is so big that entrepreneurs have founded businesses promising to identify genuinely ill research subjects. The companies use video links to screen patients at central locations where (contrary to the practice at centers where trials are run) reviewers have no incentives for enrolling subjects. In early comparisons, off-site raters rejected about 40 percent of subjects who had been accepted locally — on the ground that those subjects did not have severe enough symptoms to qualify for treatment. If this result is typical, many subjects labeled mildly depressed in the F.D.A. data don’t have depression and might well respond to placebos as readily as to antidepressants.

Related to both one and two, he says more focused studies are more accurate than more diffuse ones, and longer-term ones more accurate than shorter-term.

I'm sure that's true, just as in psychology and sociology. And, that's exactly where we're at with depression - a juncture of medicine and the social sciences.

Why has the media bought into the "antidepressants don't work," then?

Kramer says, indirectly, it's a mix of media liking "hot" stories and the "Big Pharma" effect.

The first will continue to be with us, and on science stories, only get worse in the future. The second will probably be made worse by Internet surfing and conspiracy thinking.

Neuroscience roundup - brains, guts, meds

Antipsychotic drugs could be shrinking brains. A large study seems to offer a fair degree of confirmation. I think, among other things, we should look more carefully at off-label use of these drugs. Smaller brains may not be bad, but ...

Meanwhile, about 50 percent of people prescribed antidepressants are off-label users. It's stuff like this that leads to "Big Pharma" cries.

You not only have a "second brain" in your gut, but your intestinal microbes may influence both that and the actual brain, through effects on neurotransmitters. Woo-ers running wild with this aside, how could this affect antibiotics prescriptions? What is antibiotic resistance going to do to this?

SSRIs no better than placebo? Not quite

The truth is, no new study claimed that. Rather, that story last week was based on meta-analysis. Regular readers know my feelings about meta-analysis. Worse yet, the meta-analysis included only 23 original studies, which in turn focused on just two antidepressants.

Hardly scientific.

Friday scatblogging — why I scatblog

It’s a protest against the inanity of catbloggers like the one giving a cat antidepressants.

What effing idiocy.

First, it might be different if it were a dog, as far as my personal animal preference.

Second, while I appreciate and understand the psycho-emotional value of pets, treating them that much like people is ridiculous. Doctors Without Borders could use that money spent on cat Elavil for the Myanmar cyclone relief, etc. A local food bank could use that too. (Some degree of apologiies to the blogger to whom I linked; she said her cat is on Elavil for urinary incontinence. The veterinary Elavil website she linked, however, lists a psychological issue, separation anxiety, as its first feline use; more on this above your head in another blog post.)

Third, this sounds like a spinoff racket for Big Pharma, as well as a direct racket for veterinarians. What next, cat whisperers, or dog whisperers, for that matter, asking patients to do primal meow or primal bark therapy?

Hell, it could be a Big Pharma spinoff for real people, too. Kid won't stop bed-wetting? Fine, here is some Elavil.

Finally, looking for new scatblogging ideas every week stimulates my creativity for blogging here.

Almost every one of my scatblogging posts, with the exception of something like the horse Scat Daddy, has been about serious issues.

Dating American Indian caves by coprolites goes to the “Clovis” issue that’s at the heart of anthropological study of American Indian origins. A challenge to identify wild animal scat encourages people to get m ore involved with nature. My multiple scatblogs about mass transit with the proper acronyms of course touches on fuel prices, the future of mass transit, etc. The blog about burning scat to fire a power plant raises a number of issues.

Even the one about the scat-porn video producer is serious in that it covered First Amendment issues. Especially given the current occupant of the White House, that’s a serious issue.

A couple more thoughts on the PLoS antidepressants study

I add these observations based on quotes the Public Library of Science report on antidepressants and their alleged minimum effectiveness on milder depressions.

First, per a comment on a blog, two of the studied drugs are SNRIs, not SSRIs. The PLoS study doesn't even list SNRIs as a type of antidepressant. I quote:

Antidepressants include “tricyclics,” “monoamine oxidases,” and “selective serotonin reuptake inhibitors” (SSRIs).

Second, would you describe improvement of more than halfway from the baseline to “significant” as “marginal”? Again, I quote:

A previously published meta-analysis of the published and unpublished trials on SSRIs submitted to the FDA during licensing has indicated that these drugs have only a marginal clinical benefit. On average, the SSRIs improved the HRSD score of patients by 1.8 points more than the placebo, whereas NICE has defined a significant clinical benefit for antidepressants as a drug–placebo difference in the improvement of the HRSD score of 3 points.

(The word "marginal" is used more than once throughout the study.)

“Moderate” or even “modest” would be acceptable words. “Marginal” overstates the case.

Next, given what I’ve already said about p values, I'm not sure how much weight I would put on a total of 5,100 people in the 35 trials umbrellaed in the meta-analysis. I'm not sure how much significance I would find in one medical study that had that many people, especially if studied over a short time period.

That said, given the “lag” anti-Ds can have, the FDA is also remiss on some of their study criteria, I don’t doubt. Is two weeks too soon to allow a drug switch? In cases of severe depression, you may feel you have to try something else, which you do for the patient's sake, of course, but that should perhaps "ding" the study in some way.

That said, given that we still know little about brain chemistry, even if anti-Ds are shown to be of little effect some day, I'm not even sure that we can, today, say they are either effective or ineffective, with any degree of confidence.

The PLoS antidepressants study, the ‘looseness’ of medical research statistics and ‘faith’ in meta-analysis

Way too loose of p-values for false positives in studies, in medicine (and social sciences) compared to natural sciences, is one reason to not read too much into any individual study that claims antidepressants are ineffective, like the Public Library of Science meta-analysis of individual studies did.

P-values of the same looseness as in medicine/social sciences have been used to claim intercessory prayer actually works on sick people (halfway down the linked page), for example, or here (two-third down the linked page):

Targ's paper is not the only questionable study on the efficacy of prayer that has been published by medical journals. The editors and referees of these journals have done a great disservice to both science and society by allowing such highly flawed papers to be published. I have previously commented about the low statistical significance threshold of these journals (p-value of 0.05) and how it is inappropriate for extraordinary claims (Skeptical Briefs, March 2001). This policy has given a false scientific credibility to the assertion that prayer or other spiritual techniques work miracles, and several best selling books have appeared that exploit that theme. Telling people what they want to hear, these authors have made millions.

Also, per a blogger, I came across a good statement on how many people misunderstand p-values in general:

First, the p value is often misinterpreted to mean the “probability for the result being due to chance”. In reality, the p-value makes no statement that a reported observation is real. “It only makes a statement about the expected frequency that the effect would result from chance when the effect is not real”.

In short, as I’ve tried to explain to people over at Kevin Drum’s blog, p values in medicine are simply too loose.

But, as the study’s authors claim, doesn’t meta-analysis take care of all those p-value problems? No.

Meta-analysis, no matter how much it’s defended, can’t totally cover that up.

I’m not saying that the results of a meta-analysis are no stronger than the weakest study in its umbrella. I am saying that, with p values as loose as they are in health/medicine (and social sciences), is that no massive amount of individual research studies being included under one meta-analysis will make the meta-analysis’ results anything more than a little bit stronger than the best individual study.

In other words, in medicine, and in social sciences, meta-analysis adds a very modest bump, nothing more. The problem is, most people believe it does much more than that when it doesn’t.

Or, to put it another way, meta-analysis is no better than the material it’s analyzing.

So, what’s needed is medical studies to continue with the p of 0.05, because we don’t want to risk screening out potentially life-saving study, but, to re-crunch research studies at the same time. I’m not saying we need to do that with a p of 0.0001, or 1/100 of 1 percent, like the natural sciences, especially physics, normally do. But to re-crunch with a p of 0.01, or 1 percent instead of 5 percent? Absolutely.

Research that made the 5 percent cutoff but not the 1 percent cutoff would be categorized as “worthy of further study but without any immediate conclusions from it being acceptable.”

A sidebar benefit would be that a lot of alt-medicine research would get a less than full imprimatur.

Prozac: No better than placebo?

A major new meta-analysis, as reported in The Guardian, makes exactly that claim. The full study, published in the Public Library of Science, is here. And, it’s not just Prozac; another major selective serotonin reuptake inhibitor antidepressant, Paxil, get the same critical nyet, as do two serotonin-norepinephrine reuptake inhibitor antidepressant:

The review breaks new ground because Kirsch and his colleagues have obtained for the first time what they believe is a full set of trial data for four antidepressants.

They requested the full data under freedom of information rules from the Food and Drug Administration, which licenses medicines in the US and requires all data when it makes a decision.

The pattern they saw from the trial results of fluoxetine (Prozac), paroxetine (Seroxat) [Paxil in the U.S.], venlafaxine (Effexor) and nefazodone (Serzone) was consistent.

“Using complete data sets (including unpublished data) and a substantially larger data set of this type than has been previously reported, we find the overall effect of new-generation antidepressant medication is below recommended criteria for clinical significance,” they write.

I think the conclusion is somewhat overstated, and meta-analysis research in general is sometimes overhyped; nonetheless, is this anywhere near bogus? I think the research probably is pretty solid.

In any case, Big Pharma is HUGELY worried and wasted no time to attack.

In adults, however, the depression-beating benefits were thought to outweigh the risks. Since its launch in the US in 1988, some 40 million people have taken Prozac, earning tens of billions of dollars for the manufacturer, Eli Lilly. Although the patent lapsed in 2001, fluoxetine continues to make the company money — it is now the active ingredient in Sarafem, a pill sold by Lilly for premenstrual syndrome.

Eli Lilly was defiant last night. “Extensive scientific and medical experience has demonstrated that fluoxetine is an effective antidepressant,” it said in a statement. “Since its discovery in 1972, fluoxetine has become one of the world's most-studied medicines. Lilly is proud of the difference fluoxetine has made to millions of people living with depression.”

A spokesman for GlaxoSmithKline, which makes Seroxat, said the authors had failed to acknowledge the “very positive” benefits of the treatment and their conclusions were “at odds with what has been seen in actual clinical practice.”

Hey, if you can remarket an antidepressant as another drug, as Lilly did by rebranding Prozac as a pre-menstrual issues drug after its patent expired, you’re going to be dollar-sensitive.

That said, as someone currently on citalopram (generic Celexa), and having run through comments on a post on this on Political Animal, I have a few thoughts.

First, if antidepressants did work BECAUSE they were placebos, why wouldn’t the placebo effect work with the first antidepressant? Why do so many people, unfortunately, try three or four before finding the right one for them?

Second, claiming a “spontaneous remission” for depression, saying that means we can and should go back to pre-drug days, is not just naïve but dangerous. Like a physical illness such as MS that goes into “remission” but then flares up again, depression can do the same.

Finally, we know too little, still, about brain chemistry to know exactly how antidepressants work. Therefore, claiming we know they don’t work is premature, even if that does prove to be the case 20-30 years from now.