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Long-term Antipsychotic Treatment and Brain Volume: a study in biopsychiatric mythology (with some exciting data, too!) 02/08/2011

Posted by ALT in Mental Health Research, Treatments.
Tags: , ,

Finally, a scientific study just comes right out and says it: “Viewed together with data from animal studies, our study suggests that antipsychotics have a subtle but measurable influence on brain tissue loss over time…”

Recently published in the Archives of General Psychiatry by Beng-Choon Ho of the University of Iowa (and a few other authors as well) “Long-term Antipsychotic Treatment and Brain Volume” has some grains of truth in it.  Unfortunately, there’s a lot of junk in there, too.  For example, see how Dr. Ho completes that ever-so-promising sentence:

Viewed together with data from animal studies, our study suggests that antipsychotics have a subtle but measurable influence on brain tissue loss over time, suggesting the importance of careful risk-benefit review of dosage and duration of treatment as well as their off-label use. (emphasis added)

(from “Long-term Antipsychotic Treatment and Brain Volume”)

It's the classic "This Is Your Brain On Drugs" with a twist... "This Is Your Brain On Drugs And If We Say It's Bad, It's BAD; But If We Say It's Time To Do A Risk-Benefit Analysis, Then Maybe It's GOOD."

Wait…?  Determining a correlation (and inferring a causal relationship as well) between antipsychotic use and brain shrinkage doesn’t make Dr. Ho want to question the use of antipsychotics… just how much and how long?  That last phrase, “off-label use,” means that Ho isn’t even questioning the prescription of atypical and neuroleptic antipsychotics for treating depression, bi-polar disorder, or “preventative prescriptions” (ie prescribing these medications before a psychotic break occurs, as our lovely media psychiatrist Dr. Chang was just talking about yesterday).  Other bloggers have pointed this out, with a completely understandable amount of outrage.

What Ho and his co-authors do in this article is interweave biopsychiatry’s mythology of schizophrenia with a scientific study that seems to contradict that myth.  Being true believers in both BIOPSYCHIATRY and SCIENCE, they can’t bring themselves to question the myth or the data, and so Orwellian paradox (ie, 2+2=5) is the name of the game.  The result is – predictably – a conflicted and rather self-defeating statement of bipsychiatric dogma.  Let’s have a look, shall we?

(Here is a copy of the full article, as well as a commentary which appeared in the journal—for your reference)

The Introduction: The party line is drawn

Schizophrenia, a common mental illness affecting 1% of the worldwide population, remains a leading cause of chronic disability among young adults. Antipsychotic medications are the mainstay of treatment because there is strong empirical evidence that these drugs reduce psychotic symptoms and relapse rates in schizophrenia patients. Even though the majority of patients receive antipsychotics and benefit from reduction in psychotic symptoms, many patients continue to have negative symptoms, cognitive impairments, and progressive brain tissue loss. The causes underlying these brain abnormalities are unclear and have been a focus of much debate and many literature reviews.

(from “Long-term Antipsychotic Treatment and Brain Volume”)

Let’s break it down.

1.  Schizophrenia as a “chronic disability.”

Actually, that depends very much on where you happen to live when your first psychotic episode occurs (as location correlates to first line treatment of choice).

In 1969, the World Health Organization [WHO] launched a study looking at outcomes for people diagnosed with schizophrenia in multiple countries.  What WHO found was that patients in poorer countries (India, Nigeria, and Columbia), were doing much better than their Western counterparts at both 2 and 5 year follow-ups.  They were more likely to be “fully recovered and faring well in society;” at 5 years 64% of these patients had no symptoms and were functioning well.  Only about 24% were “doing poorly.”  Compare this to Western schizophrenics: at 5 years, only 18% had no symptoms and were doing well, while 65% had poor outcomes (were suffering chronically).  One of the biggest differences in treatment was the use of neuroleptics in the richer, Western countries, but not in the poorer countries.  (Another big difference was the existence of more informal/community supports in the poorer countries).  This study was replicated, with some stricter criteria to facilitate better comparison, in 1992 (studying only 2 year outcomes this time, however) – with almost the same results.  In poorer countries where lay counselors, societal supports, and low usage of antipsychotics are the norm, outcomes are better and schizophrenia isn’t chronic (ie recurrent and lasting over time) for over 2/3 of those who have an initial episode.

[citation for study: J. Leff, “The International Pilot Study of Schizophrenia; Five-Year Follow-Up Findings,” Psychological Medicine 22(1992): 131-145.]

Emil Kraepelin

Furthermore, it turns out that the inventor of the term “schizophrenia,” German doctor Emil Kraepelin, was actually studying a group largely composed of patients suffering from a brain virus called encephalitis lethargica, “sleepy sickness.” His diagnostic criteria then were naturally flawed — reflecting the poor prognosis for people suffering from this brain disease:

In the late 1800s, when Kraepelin was doing his pioneering work, encephalitis lethargic was not a known disease.  Anybody suffering from it would have been dumped into the pool of lunatics housed in asylums.  This was the patient pool that Kraepelin had tried to sort out, and as he’d done so, he’d identified a common type of patient… that had peculiar physical symptoms.  In addition to their mental and emotional problems, these patients walked oddly and suffered from facial tics, muscle spasms, and sudden bouts of sleepiness.  Their pupils reacted sluggishly to light.  They also drooled, had difficulty swallowing, were chronically constipated, and were unable to complete willed physical acts.  These patients apparently suffered from a global illness, which affected their mental, emotional, and physical spheres, and these were the patients most likely to become demented [ie, chronic/morbid].

(Robert Whitaker, Anatomy of an Epidemic, p 166)

An epidemic (at first referred to as “epidemic schizophrenia”) in 1916-1917 led scientists to discover that these symptoms were in fact caused by a virus, encephalitis lethargica.  And that once the epidemic waned in the 1920s, so too did the cases of “schizophrenia” that matched Kraepelin’s criteria.  Thus, the diagnostic criteria for schizophrenia were altered drastically.  But the initial belief in the morbid and chronic nature of schizophrenia (based on its confusion with that virus), remained…

2.  Antipsychotics are the mainstay of treatment because they have been proven (empirically) to be effective in reducing psychotic symptoms and relapse rates.

Not only does Ho partially negate the first assertion (antipsychotics reduce psychotic symptoms for patients) in the next sentence, he’s only got one citation here to back up the second, and it’s for a literature review (as opposed to multiple citations for actual clinical trials).  That’s a red flag right off the bat.

Going beyond Dr. Ho’s measly citation (singular), it’s easy to find important and well-reputed studies that directly contradict this.

Just one example: in a 1971 NIMH [National Institutes of Mental Health] study involving 310 participants, the higher the initial drug dosage, the more likely relapse became.  The group with no dosage at all had the lowest relapse rate; 7% of the no dosage group relapsed, as opposed to 45% of those who were placed on neuroleptics and then withdrawn.  Check out Robert Whitaker’s Mad In America, Chapter 7: “The Patient’s Reality” for a much more comprehensive review of the literature surrounding antipsychotics, their propensity to both cause and worsen relapse (even in those who maintain and recommended dosage instead of withdrawing).  Also relevant is the work of Dr. Mosher on non-medication therapies involving social supports that are very effective at preventing relapse.

[citation for study: R. Prien, “Discontinuation of Chemotherapy for Chronic Schizophrenics,” Hospital and Community Psychiatry 22 (1971): 20-23.]

Comments and Conclusion: Don’t cross that line!

Dr. Ho poses a question in his comments: Are antipsychotic-associated GM [grey matter] and WM [white matter] volume reductions “bad” for patients?  He frames his answer in terms of a risk-benefit ratio:

If antipsychotics do indeed result in deleterious brain tissue volume reductions, how does this influence the risk-benefit ratio of antipsychotic treatment? Given that these medications have substantially improved the long-term prognosis of schizophrenia and that schizophrenia is a disease with significant morbidity, continued use of antipsychotics is clearly still necessary. However, our findings point toward the importance of prescribing the lowest doses necessary to control symptoms. (emphasis added)

Per our discussion above, we’ve already determined that Ho’s 2 “givens” are anything but that… there’s significant scientific (and even more anecdotal/experiential) evidence to the contrary.  More specifically, this body of research implicates “antipsychotic treatment” as the main aspect differentiating when schizophrenia is chronic and morbid and when it is not!  Kind of like the opposite of what Dr. Ho says.

Ultimately, the conclusion of this study involves Dr. Ho playing both sides of the PR game.  First, he asks the relevant, tough question (“Is brain shrinkage bad?”) and then answers an entirely different, softball question (“Why should patients keep taking their pharmaceuticals?”).  Bravo.  His funders (Jannssen, et al) would be proud.

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1. Jane - 02/09/2011

It is Orwellian doublespeak.

“It’s bad, but, it’s necessary, because it’s also good!”

Good post.

2. C. McCoolicuddy - 02/11/2011

So much to be learned by reviewing the point of departure of a “science” and the map used to reach its destination. I wonder where it is going and will there be buried treasure at the big x. Great detective work on your blog.

3. Matt Scarrock - 03/02/2011

Hi, this is a good post. I have studied the mixing of antidepressants an antipsychotics as well as benzos in my article: http://www.drugfreeminds.com/drugs

I’m pretty sure – after an extensive research – that the effects of these drugs are much more extensive than we are let to believe. I have suggested that long-term usage of any of these drugs will cause similar side effects because of the way brain works.

I truly believe you can study antipsychotics by reading an antidepressant related articles and vice versa. I accept not everyone agree with me on this.

Rhiannon Griffith - 03/03/2011


Good article (the one by Matt.) (The one by alt-mentalities is brilliant as usual of course!)

Matt, you are not alone in your conclusions. I think the neuroscience points that way inevitably and obviously. There are differences across the types of drugs, it’s true, as far as exactly what they perturb (for example, some of them screw up hormones more than others, and hormones have so many effects); but overall, with multidrug cocktails and/or use of different drugs over many years, the end result is just plain chaotic perturbation of brain chemistry and function, which looks a lot the same regardless of which drug screwed it up first.

IMO, of course. Anecdotal evidence and speculation based on what we think we know of the cell biology and chemistry of the brain. Wish we had the actual science. In my dreams.

Take a look at Anatomy of an Epidemic, if you haven’t. And maybe my blog (http://prhii.squarespace.com). I’ll probably be linking to yours.


altmentalities - 03/04/2011

Rhi –

Thanks for the encouraging words. Your blog is lovely; I like your style. Very funny about the pajama/fashion philosophy… that’s also me in a nutshell (and all my friends tease me about it)! I haven’t gotten to Anatomy of an Epidemic yet; but Mad In America is a regularly quoted item on these pages. A very good read. Robert Whitaker is an excellent speaker, too — in my opinion, a good one for people who haven’t jumped off into the alternative psychiatry deep end yet because he’s so darn calm, collected, scientific, and… normal. I especially like this lecture of his. Basically, Anatomy of an Epidemic in 45 minutes.


4. Matt Scarrock - 03/04/2011

Hi, thanks for the lecture link and the feedback of you both! I didn’t know your site Rhi before – I’ll go and read it right away :)

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