November 9, 2006

Massacre of The Unicorns

The real problem of a critique of our own cultural models is to ask, when we see a unicorn, if by any chance it is not a rhinoceros.

It’s a convenient fiction that the difficulties with psychiatric diagnosis and treatment are due to incomplete knowledge- if we just knew more about dopamine!—but the real source of the failings is inherent in its structure.  Psychiatry fails because it is designed to fail.  (continued below...)




Massacre of the Unicorns





The real problem of a critique of our own cultural models is to ask, when we see a unicorn, if by any chance it is not a rhinoceros.[i]




It’s a convenient fiction that the difficulties with psychiatric diagnosis and treatment are due to incomplete knowledge- if we just knew more about dopamine!—but the real source of the failings is inherent in its structure.  Psychiatry fails because it is designed to fail.



Semiotics and Psychiatry


The problem is with the signs of psychiatry.  Signs are vehicles for conveying information.  For example, the term “antidepressant” is a sign conveying the idea of a “drug which treats depression.”  While tricyclics and SSRIs are both called “antidepressants” because they treat depression, the term otherwise carries no necessary value except that.   Signs can be misused if they are expanded to take on new meaning in an inconsistent fashion.    Consider the controversy over “antidepressant induced mania.”  Tricyclics have been shown to be associated with higher manic rates, but SSRIs haven’t. So does that mean that most textbooks and articles are wrong—that antidepessants don’t cause mania?  Actually, the problem is worse than that.  It’s not that antidepressants don’t  cause mania—it is that there cannot be any such notion as antidepressant induced mania.


Hydrochlorothiazide (a diuretic) and propanolol (a beta blocker) are both “antihypertensives,” but otherwise are very different drugs with very different side effects; only one makes you pee.    There’s no such thing as “antihypertensive induced peeing.”


But this error is itself based on an earlier semiotic error, with the sign of “bipolar disorder,” and its implicit idea of two opposing poles.   Depakote will cure and prevent mania; and Zoloft will cure and prevent depression.   The treatment of one pole should surely move the patient closer to the next pole;  hence, psychiatrists talk about “antidepressant induced mania” but “Depakote breakthrough mania.”   See the difference?  No?  That’s because, in reality, there is no difference in the two manias, and absolutely no reason one should believe one is “induced” and the other “breakthrough,” except that the problem has arbitrarily been defined in this manner, i.e. a) mood stabilizers are a priori preventative, and b) Depakote is a mood stabilizer.  But a) is a postulate and b) is an optimistic assumption.


A similar example is the often cited myth that diagnosis of bipolar disorder is frequently missed.  A survey[ii] found that 69% of patients were actually misdiagnosed, most often as having regular depression.  An average of 4 physicians were consulted “prior to receiving the correct diagnosis.”  But who is to say what is the correct diagnosis, when the diagnosis is based on vague and overlapping descriptions (and not on objective pathology?)  You can look at this the other way, and say only 1 out of 5 psychiatrists felt it was bipolar disorder, while the other 80% thought it was depression.   So it pays to have the last word.  Bipolar disorder is “frequently missed” not because it exists and doctors miss it, but because it is defined in a way which allows it, by 80% of doctors, to be legitimately called something else.  The only way to say the diagnosis was correct or incorrect, in the absence of objective pathology, is to say that the treatment they received for “bipolar disorder” from the fifth doctor was better (read: safer or more efficacious) than the treatment they received from the first four.  This is not evident. 


Marco Polo's Dilemma


The problem in psychiatry is the problem in the epigraph at the beginning of the paper.  When Marco Polo saw the exotic one horned quadruped, his frame of reference required that it could be none other than a unicorn, even though it did not conform exactly to his prior conception of it.  Marco Polo made his observation fit his existing paradigm of zoology.  While superficially (and in retrospect) this may seem silly and arbitrary, it is in fact the opposite, Marco Polo believed  the only thing he could believe—because the alternative was to believe he had discovered an entirely new, unheard of, creature.  This is the semiotic problem in psychiatry, wherein we are forced to interpret clinical signs with our available “encyclopedia,” because we lack both the newer encyclopedia, and its accompanying language, to interpret the signs differently.  But here’s the extra credit question: is it really a rhinoceros or a unicorn?    


Psychiatry is trying to move away from a symptom based field to a disease (or at least disorder) based science.  We are deciding (note word choice) that a psychiatric disease exists a priori, and can present with different symptoms, the way cancer could present as the flu, but really is cancer.  The diagnosis (or sign) becomes more important than the individual symptoms, because it demands a specific treatment.  But if the paradigm is faulty, what of the treatment?


An example is the association of bipolar disorder with mood stabilizer.  Through a series of laughable twists,  psychiatrists came to believe that antiepileptics had special properties in bipolar because they could quell the chaos in the brain in the same way that they calmed seizure activity there.   It is now common practice,  as defined in numerous “Expert” guidelines and consensuses, that patients with bipolar disorder need to be on a mood stabilizer, specifically lithium or the antiepileptic Depakote.  The problem with this is that there has never been a study that found that Depakote is a mood stabilizer.  In fact, there is no evidence that any antiepileptics are mood stabilizers.  What few studies have been done show no benefit over placebo for this purpose.  Remarkably, very few psychiatrists know this.  But worse, even when you show them data, they refuse to accept it.


I know, it seems—well, crazy—that psychiatrists would blatantly ignore the absence of data—the opposite of data.  Ask your psychiatrist the following question:  A patient with a history of bipolar disorder presents depressed.  There are only two medications available: Prozac or a new antiepileptic for which no efficacy or safety data yet exist.  Which do you use?  That the mystery antiepileptic is even considered shows the power of the association, because I haven’t actually told you anything about the antiepileptic.  Nothing about efficacy, safety, anything.  And a doctor would consider it?  It’s considered because it is assumed that it will share the same properties as other antiepileptics, i.e. that it is a mood stabilizer.  But no other antiepileptics are mood stabilizers, so why the assumption?  And even if one seizure drug was, in fact, a mood stabilizer, why would another one be?  If antiepileptics have totally different efficacies with respect to seizure treatment, why should it be any different for bipolar treatment?   The power of the paradigm compels us. 


Can an antipsychotic be an antidepressant? Sure.  Can an antidepressant be an antipsychotic?  See?  You’re hesitating.  It is harder to imagine that an antidepressant can be an antipsychotic—as if there is anything in either term that allows us to predict other actions—because the paradigm has given value to terms that they don’t have.


There’s an analogy in the social sciences: racism.


The Knowledge Trap


But psychiatry is an applied discipline.  What’s the harm if assumptions lead to efficacious treatments?  This is a trap.  Psychiatry has convinced itself that it needs to focus on expanding its knowledge (i.e. data)  rather than re-evaluating its postulates and paradigms.  New discoveries or information are used to build on a paradigm, not to test it.  But now psychiatry is looking to see what it expects to find. And if a discovery flatly contradicts the tradition, then it is ignored or rationalized.  How else to explain the comparative absence of articles critically discussing the placebo response?  And the even fewer whose proposed solution is not the abandonment of the placebo arm, in favour of “active controls.”  Active as defined by whom?  Is Depakote an active control?


What Is Modern Psychiatry Seeking?


The fiction is that psychiatry is looking for more efficacious treatments.  It is not.  It is looking for different treatments; the paradigm does not allow for the creation of better treatments.  For example, psychiatry can applaud itself from moving from a “noradrenergic hypothesis” to a “serotonin hypothesis” of depression, but it’s still the same paradigm.  While first line medications have changed, they have not changed because of improved efficacy.  Nothing has ever found anything to be more efficacious than the previous standard (SSRIs. vs. tricyclics, atypical antipsychotics vs. chlorpromazine, etc.)  nor has any “model” been more or less correct than any other.  That some medications have less side effects and greater versatility is useful, but a) this is almost never the result of intentional scientific discovery but rather the fortunate by-product of the invention of (yet another) efficacious treatment; b) this greater tolerability in no way reflects the accuracy or inaccuracy of an existing model.  That Zoloft is more tolerable than imipramine has nothing to do with the viability of the “serotonin hypothesis.”  And yet how many times have I heard that antipsychotics treat depression with no more rigorous explanation than because of their “activity” (note the vague term) on serotonin?


Psychiatry, which seeks to be like physics, becomes instead a caricature of it.   It, too, tries to focus on expanding knowledge and not re-evaluating its principles.  But unlike physics, psychiatry has no formal principles.  They are made up.  It is, strictly speaking, not a science but a paradigm, no different than psychoanalysis.  It may seem as though Freud concocted the notion of the unconscious out of thin air and developed an entire field around it, but modern psychiatry has done nothing different in concocting the notions of kindling or “upregulation of receptors” as first principles and then constructing an equally arbitrary field around them.  That medications help patients has everything to do with the medications and nothing to do with the incense and liturgy that surround them.


Paradigm shifts do not occur in physics because the principles do not change.  Newtonian mechanics will always be useful for prediction because it is correct for the cases in which it is applicable (i.e. for measurable bodies.)  It is furthermore not susceptible to political influence.  Psychiatry is the opposite.  The decision to accept or reject the paradigms in psychiatry are very clearly political, not evidentiary.  We as individuals accept the idea that antiepileptics are mood stabilizers because psychiatry has decided to adopt this position, not because the evidence requires us to accept it (in fact, the evidence should require us not to accept it, or at least seriously question it.)  No physicist could hope to “practice” physics without having read and understood what came before, without having worked the “block on an incline” problem.  But there is no theoretical nor practical requirement to practice psychiatry of reading the papers on, for example, mood stabilization, let alone what came before.  All that is required is to know what the current practice is (“Guidelines recommend prescribe antiepileptics.”)  This may seem like science, i.e. “scientists have determined that antiepileptics are mood stabilizers, so we will trust their word and prescribe them,” but it is very clearly politics.


The current problem of psychiatry is that it seeks to be something that it is not: science.    It may be, at some future date, readily described by scientific principles, but this is assuredly not the case now.   It is most certainly a sociological construct, a paradigm, with a shared educational system, shared assumptions, and a mechanism to communicate discoveries (i.e. journals, meetings.)  It also has a common language.  But it lacks the  predictive ability common to other disciplines.


An argument against the notion that psychiatry is an arbitrary paradigm is that it is a reflection of what actually occurs in the brain.   This is sophistry.  For example, saying   the “serotonin system is relevant in mood disorders” is empty because it lacks context.  Does it mean that no other system is relevant?  Or that it is the most relevant?  Or even necessary?  Sufficient?  What about Wellbutrin?  Are you saying psychotherapy alters serotonin?  (And not dopamine?  Etc) 


Why There Can Be No Progress in Biological Psychiatry Using The Current Paradigm


While there is a science of the brain, there is no science of thought.  Another way to think of the problem is to question the nominalism of the field.  Psychiatry talks about things like mood, emotion, depression.  But are those actually real and distinct things?  Is there some signal pattern in the brain that is mood that is wholly unrelated to the signal pattern for a thought?  Just because something has a name, that does not mean that the thing exists in fact.  These may be simply convenient fictions.


To say that because it is known that chemicals can alter what is called mood therefore proves the existence of mood is not satisfactory.  The death of a loved one will alter mood as well, often dramatically and to an extreme. How is this possible, if no chemicals are introduced into the system? In fact, nothing new is introduced into the brain except, depending on the paradigm, a) information or b) energy (i.e. converted sound waves.)  How does the introduction of a new piece of information trigger an alteration of mood?  Why would one thought "My family is dead" trigger the release of some chemicals, but another thought "My family is alive" not trigger that same release?  And how does a non-physical entity like a thought trigger a physical reaction?  Are thoughts even discrete? Or does the brain operate on a flow of thoughts?  Digital or analog? 


Linear regression and statistics cannot address all of the problems of chemistry and mood;  for one reason because it does not account for thoughts that a patient cannot have while on the drug-- but it is reasonable to think there are some.  In other words, if there is some set of thoughts A, a subset B of which are negative and a subset C of which are positive, then is the introduction of a chemical in the brain able to block only subset C, or does it simply block set A? The reverse is potentially applicable: that there are certain thoughts that can be had only when on a drug.  (This is obviously evident in the case of perceptions that can be had only on a drug.)


The simple analogy to computer hardware and software illustrates the difficulty in psychiatry.  One can understand all of the hardware of a computer system, but this will not explain if or how the computer can run word processing software, video games, instant message or be susceptible to a virus, or make any predictions about the behavior of this software in the real world (for example, no computer technician could predict the writing of this paper, nor, by changing the hardware, alter the content of this paper.)   Hardware is finite, but software is infinite, or as infinite as is thought.  Without understanding the mechanism of thought, or at least how thoughts or states can affect mood, then a pharmacology of the brain will simply tread water with no progress towards either treatment or diagnosis.  One cannot permanently alter mood without at least simultaneously altering thought.  In a sense, there is more logic to the psychological approach, or at least in conjunction with medications, because if software (thought) is the problem, more software is the cure.   While the applicability of “therapy” in schizophrenia may be debatable,  there is no reason as yet to decide that any other approach is applicable to mood disorders such as depression or anxiety, and absolutely no evidentiary reason to assume that pharmacology is the superior approach.  It is not necessarily faster nor more consistently reliable.


Myths of psychiatry such as those described above are not isolated examples of poor practice or lack of knowledge, but are the unavoidable manifestations of an artificial paradigm which is arbitrarily derived from unproven assumptions, justified by inappropriate logic.   They often lead to ineffective, dangerous, and very expensive treatment.  Psychiatry must be more vigilant about its own data.   It is necessary  to avoid laziness in our education and understand from where comes our knowledge.  There are daily diatribes against the influence of pharmaceutical companies; but the effect of pens and detailing is surely much smaller than the effect of misunderstood data, poorly researched axioms, and signs run amok.  Psychiatry will not survive as a medical subspecialty if it continues along this path.  It will lose its dignity, and worse, it will become irrelevant.



“It would be good to conclude by recommending a short book, What Is Science?, that does things the right way. It takes a robustly objective view of the relation of evidence to conclusion, explains what laws of nature are, briefly shows how measurement, data, statistics, and mathematical models work in science, states which parts of science are well-established and which not, illustrates with engaging episodes in the history of science, and ends with some colorful rudenesses on postmodernist solecisms concerning science. Unfortunately, it does not exist.”[iii]


[i] Eco, Umberto (1998). Serendipities: Language and lunacy (William Weaver, Trans.). New York, NY: Harvest.

[ii] Hirschfeld RM, Lewis L, Vornik LA.   Perceptions and impact of bipolar disorder: how far have we really come? Results of the national depressive and manic-depressive association 2000 survey of individuals with bipolar disorder. J Clin Psychiatry. 2003 Feb;64(2):161-74.

[iii] Franklin, James.  Thomas Kuhn’s irrationalism.  The New Criterion Vol. 18, No. 10, June 2000


Despite no evidence of the ... (Below threshold)

December 26, 2006 1:19 AM | Posted by Nonshrinkable: | Reply

Despite no evidence of the author's name, "Massacre of the Unicorns" is claimed to have been written by S. Nassir Ghaemi

This is proof of what self-shrinkage does to a person...he belongs in the farthes neck of the woods with the other squirrels collecting nuts for the winter.

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December 31, 2006 10:42 AM | Posted by Kevin: | Reply

I found this article (an others on your site) to be a disturbing eye-opener, especially your criticism of how we prescribe meds. You’re obviously extremely well versed in the psychopharm literature, and I believe that part of the solution your propose is that we all achieve your level of knowledge of (and ability to scrutinize) the literature supporting what we do. Although ideal, I think this is unrealistic, which is why we rely on the “Expert” guidelines you so criticize:

“It is now common practice, as defined in numerous “Expert” guidelines and consensuses that patients with bipolar disorder need to be on a mood stabilizer, specifically lithium or the antiepileptic Depakote.”

As a busy PGY-2 trying to learn psychopharm I rely on basic texts and expert opinions, i.e. the APA guidelines. You place “expert” in quotations – suggesting that they are not valid or trustworthy.

The APA states the following about the APA guidelines:

“Developed by expert work groups, who review available evidence using an explicit methodology. Iterative drafts undergo wide review by experts, allied organizations, and any APA member on request. Every guideline is also reviewed and approved for publication by the APA Assembly and Board of Trustees. The development of APA practice guidelines has not been financially supported by any commercial organization.”

So, if I can’t trust this process…carried about by the governing body of our profession, then what can I trust? It seems your answer is to become as versed in the literature as you. I find residency challenging and formidable enough. If I can’t rely on texts and APA guidelines, and instead have to comb through PubMed and try to make sense of the data myself, then I give up. Isn’t that what the APA is already doing in developing the guidelines? Our IM colleagues utilize all sorts of guidelines (e.g. JNC-7) that they seem to trust. What I’m afraid is…is that you’re right. And if you’re right, then my residency is training me to be another cog in the machine that you fear “will not survive as a medical subspecialty if it continues along this path. It will lose its dignity, and worse, it will become irrelevant.”

So, what do you recommend I do? I don’t mean this to be sarcastic. I’m a resident working 60-70 hours a week, and I’m trying to read at least a couple hours a week. What should I be reading? It seems that everything I’m reading, according to you, is just teaching me “artificial paradigm(s) which (are) arbitrarily derived from unproven assumptions, justified by inappropriate logic.” I’m telling you, I can’t start from scratch and start reviewing the literature on every drug, and drug-combination, ever devised. I wish I could. Honestly. If everything you’re saying is true, then the solution is not that everyone become as knowledgeable as you, but instead…we need evidenced-based guidelines that you’d find acceptable. Do you think that’s unattainable?

Please don’t interpret me incorrectly. I don’t mean to say that we all shouldn’t strive to be well-read on the primary literature. And I agree we should all become better equipped to scrutinize the “research” (see, you’ve got me using skeptical quotes now) that’s paraded before us by the Pharm Reps.

Again, what do you suggest I start reading? I’ve been studying the APA guidelines, K&S, the APA Board Review Book, and recently, the Janicak Principles and Practice of Psychopharm. (Which, btw, states that “DVPXis the best-studied of the mood stabilizers and is emerging as a highly effective alternative treatment to lithium for acute mania,” which is in direct contrast to your contention that “there has never been a study that found that Depakote is a mood stabilizer” and that “few studies have been done show no benefit over placebo for this purpose.”)

If my reply to all this sounds contentious, it’s not. I am frustrated that everything I’m reading turns out to be wrong.

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August 20, 2007 3:17 PM | Posted by katielou82: | Reply

I am a patient, not a doctor. Being the patient and not some outsider to my life I tend to be very interested in "getting to the bottom of things", when it comes to what is going on with my brain.

And so: I spend hours almost every day searching PubMed and trying to put the paces together. ( I know, I should become a doctor, it is all very interesting to me)

Any med my doc suggests I do hours of research on, unless I am actually so sick that I know I shouldn't be giving myself any excuses to get freaked out and not take the med. If I need instant relief I'll trust the doc and throw it down the hatch as soon as I get home with my shiny new Rx....although in the past this has caused me some serious mental problems (you say antidepressant induced mania doesn't exist? well what would the best term be for someone going completely freaking bonkers any time an AD is added to the mix? just one of the many adverse reactions anyone could have?... not indicative of BP? -I am just curious, and perhaps I missed the point)

Any question that pops into my head on any given day I do a few hours of research on. And most of my questions these days revolve around psychopharmacology, BP and other MIs.

It is frustrating because what I come up with is this:
everything is conflicting and no one really knows anything about how MI works or why meds help some people.
There are plenty of ideas and theories... but no real scientific consensus.

YAY! that really makes me feel like it's a great idea to treat my BP with all these pretty damn toxic meds. Especially when six out of eight times I have had either a bad reaction to a med, ie it made me feel worse from the get go, or it helped for a while and then again, made me feel worse.

just freakin hooray for psychiatry. It must be a horribly frustrating field to be in if you're one of the people who is paying attention.
I know as a patient who is paying attention it is...well scary.

I already knew from the get go that psychiatry was nowhere near an actual science.... I was just hoping that there was SOMETHING to it.

In anycase, I had taken to the idea of using supplements to help myself out about six months ago. And to my amazement DLPA, 5HTP, Tyrosine and some other amino's have done more for my sense of wellbeing and sanity than any medication ever has.

I had expected some sort of vague benefit from OTC supplements and was very surprised when I discovered these things work within 45min to 2 days (depending on how long I wait letting myself feel blue or drained etc. before taking them). I was very surprised to find that they worked better than any antidepressant I have ever tried, and that I can take them as needed. I really had thought that maybe only after a month or two of taking these things I would start to feel an effect if they were going to work at all. Goes to show you the high expectations that psychiatric drugs had set me up with.

I just sometimes wonder if perhaps psychiatry is looking at things all wrong. That maybe nutrition is very important part of treating the milder phases and presentations of things like depression and bipolar. Maybe even a way to keep some of them from progressing?

At least the psyche docs are on board with sending people to therapy. Changing how you think is defiantely an important way for anyone to cope better in the world.

But the amino acid thing seems to help a LOT of people, even when years of psyche meds have failed them.
They seem safer, so maybe they should be used as a first approach in some cases. Or at the least an adjunct to medications instead of adding even more medications.

If only there was enough money to be made off food based supplements.... we might actually have some treatment options that are actually treating the cause ( I am pretty convinced that in some people not getting enough of certain amino acids to the brain is the cause... the brain needs enough of certain food stuffs to work don't it?) and not just the symptoms.

I mean seriously... how can nutrition be discounted and ignored the way it is? I'm not saying that every case of MI is some deficiency in absorption or weird modern malnutrition. But the idea should be further explored. Meds can help a lot of people, but they can also be toxic, and a lot of people don't get better with them. A psychiatrist ought to be able to say "well maybe you should try 5HTP before we add an antidepressant to the mix", to a patient that is not so depressed they are on the brink of suicide, or incapable of showering and getting to the store to buy the stuff etc.

Well that's my two cents. And if you can, if you haven't already (I need to search the site to check), could you do a post about nutritional approaches. I would like to read your take on it.

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September 10, 2007 8:55 PM | Posted by Kufjqbob: | Reply

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