Psychiatry Has Its Head In The Sand: Royal College Of Psychiatrists Rejects Discussion Of Crucial Research On Antipsychotics

via Mad In America;

Psychiatry Has Its Head In The Sand: Royal College Of Psychiatrists Rejects Discussion Of Crucial Research On Antipsychotics

Joanna Moncrieff, MD

December 20, 2013

Two pieces of research have been published over the last two years that should prompt a major reorientation of the treatment of schizophrenia and psychosis, and a fundamental reappraisal of the use of antipsychotic drugs in general.  Put together, these studies suggest that the standard approach to treating serious mental health problems may cause more harm than good. Long-term treatment with antipsychotic drugs has adverse effects on the brain, and may impair rather than improve chances of recovery for some. Many people ask me how the psychiatric profession has responded to this data. Surely, they think, it must have stimulated a major debate within the profession, and some critical reflection about why it took so long to recognise these worrying effects? Sadly, this does not appear to be happening.

I have described both of these studies in detail in previous blogs. Briefly, in 2012 the research group led by Nancy Andreasen, the former editor of the American Journal of Psychiatry, publishedresults of a brain scanning study of people diagnosed with schizophrenia or psychosis. The study found that people’s brains shrank over time in proportion to the amount of antipsychotic drugs they had been exposed to. The report concluded that  ‘antipsychotics have a subtle but measurable influence on brain tissue loss over time‘^{(1, p 128)}.  The study confirmed that the brain shrinkage observed in animals⁽²⁾ also occurs in humans.

We don’t know whether these observed effects of antipsychotic treatment are temporary or permanent, and we don’t know whether they have any functional implications. In other words we don’t know whether the brain shrinkage is associated with intellectual decline or other brain-based abnormalities. The evidence is conflicting, with some studies suggesting there is no impact on mental ability⁽³⁾, but worryingly, other studies, including Andreasen’s study, indicate that there may be an association between reduced brain volume and some cognitive or mental deterioration^(4;5). It is obviously a worrying possibility.

The second game changing publication was the paper reporting the seven year follow up results of the Dutch antipsychotic discontinuation study⁽⁶⁾. This study, conducted with people who had recovered from a first episode of psychosis, found that people randomised to a flexible and gradual antipsychotic discontinuation strategy were twice as likely to show a full social recovery than those who were allocated to continuous (maintenance) antipsychotic treatment. Moreover, relapses, which had been higher in the discontinuation group at 18 month follow up, had equalised.

As I have said elsewhere, I am not against the use of these drugs altogether, but these studies suggest that antipsychotics are bad for the brain and can reduce people’s social functioning when used continuously over long periods. When I present these findings to audiences of non-psychiatrists, they are shocked that the drugs can continue to be so freely used in the face of this evidence. ‘How can this be ethically justified?’ someone commented at a recent meeting I attended.

When people ask me how psychiatrists have responded, I have, up to now, tried to give my profession the benefit of the doubt.  Some leading psychiatrists have been publicly critical of the overhyping of antipsychotics⁽⁷⁾ and there are undoubtedly many others who are concerned about these research findings and trying to avoid antipsychotic drug treatment if possible, and use low doses for short periods where not. I have expressed the hope that as this research becomes more widely known, others will follow suit.

My illusions were recently shattered, however, by the Royal College of Psychiatrists’ conference planning committee.  Recently I proposed a symposium for the 2014 annual conference entitled ‘Re-Evaluating Antipsychotics – Time to Change Practice?’ I invited Lex Wunderink, the first author of the Dutch study, to discuss his study, along with a leading British psychiatrist involved in brain scanning studies of people with schizophrenia. I was confident the symposium would be accepted, because obviously, I thought, the conference committee would recognise the importance of this research, and want to ensure it was widely publicised to, and debated by, members of the profession.

To my astonishment it was rejected. I wrote to the conference organiser to ask why, pointing out that patients, carers and the general public are wondering what the profession is doing about these research findings. They would be most surprised to know that the profession did not consider the results sufficiently interesting to merit discussion at the principal meeting of UK psychiatrists. She replied that there were too many competing suggestions. So I asked if any of the symposia selected covered these same areas of research.  I did not get a reply.

Surely, these findings are so momentous they deserve a whole conference in themselves? Every department of psychiatry around the country should be considering the implications of these studies, and be thinking about how psychiatric practice should change as a result. Yet the representative body of UK psychiatrists feels the evidence is not worthy of an hour and a half’s discussion at its annual conference.

Although I would like to believe it is was an aberration, I fear that the conference committee’s view is a barometer of the profession’s general attitude. It seems not to be interested in discussing the serious harm its drugs can do to both physical and mental health, and in taking the steps necessary to minimise this harm. The profession appears to believe that if it keeps quiet about these inconvenient findings, and discusses them as little as possible, the fuss will blow over and nothing need change.

It is disgraceful that the profession is not taking these findings more seriously, but sadly not unprecedented.  In the 1970s, the profession was accused of being ‘completely unconcerned’ about emerging evidence on the association between antipsychotic use and the syndrome of brain damage called ‘tardive dyskinesia’⁽⁸⁾.

At best psychiatry appears indifferent and complacent. At worst it is subconsciously attempting to hush up inconvenient data, so that, along with its partner, the pharmaceutical industry, it can continue ‘business as usual.’ Either way, it appears that the critics are right: the profession has its head firmly in the sand.

References:

(1)    Ho BC, Andreasen NC, Ziebell S, Pierson R, Magnotta V. Long-term Antipsychotic Treatment and Brain Volumes: A Longitudinal Study of First-Episode Schizophrenia. Arch Gen Psychiatry 2011 Feb;68(2):128-37.

(2) Dorph-Petersen KA, Pierri JN, Perel JM, Sun Z, Sampson AR, Lewis DA. The influence of chronic exposure to antipsychotic medications on brain size before and after tissue fixation: a comparison of haloperidol and olanzapine in macaque monkeys. Neuropsychopharmacology 2005 Sep;30(9):1649-61.

(3) DeLisi LE, Hoff AL, Schwartz JE, Shields GW, Halthore SN, Gupta SM, et al. Brain morphology in first-episode schizophrenic-like psychotic patients: a quantitative magnetic resonance imaging study. Biol Psychiatry 1991 Jan 15;29(2):159-75.

(4) Gur RE, Turetsky BI, Bilker WB, Gur RC. Reduced gray matter volume in schizophrenia. Arch Gen Psychiatry 1999 Oct;56(10):905-11.

(5) Gur RE, Turetsky BI, Bilker WB, Gur RC. Reduced gray matter volume in schizophrenia. Arch Gen Psychiatry 1999 Oct;56(10):905-11.

(6) Wunderink L, Nieboer RM, Wiersma D, Sytema S, Nienhuis FJ. Recovery in Remitted First-Episode Psychosis at 7 Years of Follow-up of an Early Dose Reduction/Discontinuation or Maintenance Treatment Strategy: Long-term Follow-up of a 2-Year Randomized Clinical Trial. JAMA Psychiatry 2013 Jul 3.

(7) Tyrer P. From the Editor’s desk. British Journal of Psychiatry 2012;201:168.

(8) Crane GE. Clinical psychopharmacology in its 20th year. Late, unanticipated effects of neuroleptics may limit their use in psychiatry. Science 1973 Jul 13;181(4095):124-8.

Joanna Moncrieff, MD

Dr. Moncrieff is a Senior Lecturer at University College London. She is one of the founders and co-chair person of the Critical Psychiatry Network. She has written three books: The Bitterest Pills,  The Myth of the Chemical Cure, and A Straight Talking Introduction to Psychiatric Drugs.

Thank You Dr. Moncrieff and MIA.

Well, what can we add to that?

You'd keep Your head 'In The Sand' too if you were selling Suicide and Homicide, . . . and suckering the Tax Payers into Paying you to sell Suicide and Homicide. 

Antipsychotics And Brain Shrinkage: An Update From Dr Joanna Moncrieff

Mad In America has;

Antipsychotics And Brain Shrinkage: An Update
Dr. Joanna Moncrieff June 19, 2013
Evidence that antipsychotics cause brain shrinkage has been accumulating over the last few years, but the psychiatric research establishment is finding its own results difficult to swallow. A new paper by a group of American researchers once again tries to ‘blame the disease,’ a time-honoured tactic for diverting attention from the nasty and dangerous effects of some psychiatric treatments.

In 2011, these researchers, led by the former editor of the American Journal of Psychiatry, Nancy Andreasen, reported follow-up data for their study of 211 patients diagnosed for the first time with an episode of ‘schizophrenia’. They found a strong correlation between the level of antipsychotic treatment someone had taken over the course of the follow-up period, and the amount of shrinkage of brain matter as measured by repeated MRI scans. The group concluded that “antipsychotics have a subtle but measurable influence on brain tissue loss”⁽¹⁾.

This study confirmed other evidence that antipsychotics shrink the brain. When MRI scans became available in the 1990s, they were able to detect subtle levels of brain volume reduction in people diagnosed with schizophrenia or psychosis. This lead to the idea that psychosis is a toxic brain state, and was used to justify the claim that early treatment with antipsychotics was necessary to prevent brain damage. People even started to refer to these drugs as having “neuroprotective” properties, and schizophrenia was increasingly described in neo-Kraeplinian terms as a neurodegenerative condition⁽²⁾.

The trouble with this interpretation was that all the people in these studies were taking antipsychotic drugs. Peter Breggin suggested that the smaller brains and larger brain cavities observed in people diagnosed with schizophrenia in these and older studies using the less sensitive CT scans, were a consequence of antipsychotic drugs⁽³⁾, but no one took him seriously. It was assumed that these findings revealed the brain abnormalities that were thought to constitute schizophrenia, and for a long time no one paid much attention to the effects of treatment. Where the effects of antipsychotics were explored, however, there were some indications that the drugs might have a negative impact on brain volume⁽⁴⁾.

In 2005, another American group, led by Jeffrey Lieberman who headed up the CATIE study, published the largest scanning study up to that point of people with a first episode of psychosis or schizophrenia⁽⁵⁾. The study was funded by Eli Lilly, and consisted of a randomised comparison of Lilly’s drug olanzapine (Zyprexa) and the older drug haloperidol. Patients were scanned at the start of the study, 12 weeks and one year later and patients’ scans were compared with those of a control group of ‘healthy’ volunteers. 

At 12 weeks haloperidol-treated subjects showed a statistically significant reduction of the brain’s grey matter (the nerve cell bodies) compared with controls, and at one year both olanzapine- and haloperidol-treated subjects had lost more grey matter than controls. The comparative degree of shrinkage in the olanzapine group was smaller than that in the haloperidol group, and the authors declared the olanzapine-related change not to be statistically significant because, although the result reached the conventional level of statistical significance (p=0.03) they said they had done so many tests that the result might have occurred by chance. In both haloperidol and olanzapine treated patients,however, there was a consistent effect that was diffuse and visible in most parts of the brain hemispheres.

The idea that schizophrenia or psychosis represent degenerative brain diseases was so influential at this point, that the authors first explanation for these results was that olanzapine, but not haloperidol, can halt the underlying process of brain shrinkage caused by the mental condition. They did concede, however, that an alternative explanation might be that haloperidol causes brain shrinkage. They never admitted that olanzapine might do this.

It seems as if Eli Lilly and its collaborators were so confident about their preferred explanation, that they set up a study to investigate the effects of olanzapine and haloperidol in macaque monkeys. This study proved beyond reasonable doubt that both antipsychotics cause brain shrinkage. After 18 months of treatment monkeys treated with olanzapine or haloperidol, at doses equivalent to those used in humans, had approximately 10% lighter brains than those treated with a placebo  preparation.⁽⁶⁾

Still psychiatrists went on behaving as if antipsychotics were essentially benign and arguing that they were necessary to prevent an underlying toxic brain disease (Jarskoget al 07 Annual review). Andreasen’s 2011 paper was widely publicised however, and it started to be increasingly acknowledged that antipsychotics can cause brain shrinkage. Almost as soon as the cat was out of the bag, however, attention was diverted back to the idea that the real problem is the mental condition.

Later in 2011 Andreasen’s group published a paper that reasserted the idea that schizophrenia is responsible for brain shrinkage, in which there is barely a mention of the effects of antipsychotics that were revealed in the group’s earlier paper⁽⁷⁾. In this second paper, what the authors did was to assume that any brain shrinkage that could not be accounted for by the method of analysis used to explore the effects of antipsychotic treatment must be attributable to the underlying disease. 

The way they had analysed drug treatment in the first paper only looked for a linear association between antipsychotic exposure and changes in brain volume, however. A linear analysis only detects an association that is smooth and consistent- in other words an association in which brain volume shrinks by a consistent amount with each increment in antipsychotic exposure. The total effect of drug treatment may not follow this pattern however. It seems from other evidence that there is a threshold effect whereby being on any amount of an antipsychotic has the greatest relative effect, with a levelling out of the impact as duration of exposure reaches a certain level.⁽⁸⁾ In any case, without a comparison group which has not been medicated, a virtual  impossibility in this day and age, it is simply not possible to conclude that the whole effect is not drug-induced.

The latest paper by this research group replicates the findings on antipsychotic-induced brain shrinkage, but also claims that brain volume reduction is related to relapse of the psychotic disorder⁽⁹⁾. Relapse was defined retrospectively by the research team for the purposes of this particular analysis, however, and not at the time the study data were collected. Moreover, the definition used does not refer to any significant change in functioning, but only to a deterioration in the severity of symptoms. But the group’s previous analysis of severity of symptoms, using data collected at the time, found that severity had only a weak association with brain volume changes, and moreover that symptom severity was correlated with antipsychotic exposure.⁽¹⁾

The most recent analysis ignores the probable association between antipsychotic treatment intensity and relapse, but it seems likely that people undergoing periods of ‘relapse,’ or more accurately deterioration of symptoms, would be treated with higher doses of antipsychotics. If this is so, and the two variables ‘relapse’ and ‘treatment intensity’ are correlated with each other, then the analysis is questionable since the statistical methods used assume that the variables are independent of each other.

So Andreasen’s group have found strong evidence of an antipsychotic-induced effect, which they have replicated in two analyses now. The predictive value of the severity of symptoms, on the other hand (which is essentially what relapse appears to define) is weak in the initial analysis, and in neither analysis was it clearly differentiated from drug-induced effects.

These researchers seem determined to prove that ‘schizophrenia’ causes brain shrinkage, although their data simply cannot establish this, as none of their subjects seem to have gone without drug treatment for any significant length of time. So even though their recent analysis once again confirms the damaging effects of antipsychotics, they conclude that the results demonstrate the need to make sure patients take, and do not stop, their antipsychotic medication. The only concession made to the antipsychotic-induced changes revealed is the suggestion that low doses of antipsychotics should be used where possible.

Yet other prominent psychiatric researchers have now abandoned the idea that schizophrenia is a progressive, neurodegenerative condition, and do not consider that Andreasen’s study provides evidence of this.⁽¹⁰⁾ Bizarrely, Nancy Andreasen is a co-author of a recently published meta-analysis which combines results of 30 studies of brain volume over time, which clearly confirms the association between antipsychotic treatment and brain shrinkage (specifically the grey matter) and finds no relationship with severity of symptoms or duration of the underlying condition.⁽¹¹⁾

What should antipsychotic users and their families and carers make of this research? Obviously it sounds frightening and worrying, but the first thing to stress is that the reductions in brain volume that are detected in these MRI studies are small, and it is not certain that changes of this sort have any functional implications. We do not yet know whether these changes are reversible or not. Of course the value of antipsychotics has been much debated on this site and elsewhere, and their utility almost certainly depends on the particular circumstances of each individual user, so it is impossible to issue any blanket advice. If people are worried, they need to discuss the pros and cons of continuing to take antipsychotic treatment with their prescriber, bearing in mind the difficulties that are associated with coming off these drugs.⁽¹²⁾ People should not stop drug treatment suddenly, especially if they have been taking it for a long time.

People need to know about this research because it indicates that antipsychotics are not the innocuous substances that they have frequently been portrayed as. We still have no conclusive evidence that the disorders labeled as schizophrenia or psychosis are associated with any underlying abnormalities of the brain, but we do have strong evidence that the drugs we use to treat these conditions cause brain changes. This does not mean that taking antipsychotics is not sometimes useful and worthwhile, despite these effects, but it does mean we have to be very cautious indeed about using them.

Reference List

(1) Ho BC, Andreasen NC, Ziebell S, Pierson R, Magnotta V. Long-term Antipsychotic Treatment and Brain Volumes: A Longitudinal Study of First-Episode Schizophrenia. Arch Gen Psychiatry 2011 Feb;68(2):128-37.

(2) Lieberman JA. Is schizophrenia a neurodegenerative disorder? A clinical and neurobiological perspective. Biol Psychiatry 1999 Sep 15;46(6):729-39.

(3) Breggin PR. Toxic Psychiatry. London: Fontana; 1993.

(4) Moncrieff J, Leo J. A systematic review of the effects of antipsychotic drugs on brain volume. Psychol Med 2010 Jan 20;1-14.

(5) Lieberman JA, Tollefson GD, Charles C, Zipursky R, Sharma T, Kahn RS, et al. Antipsychotic drug effects on brain morphology in first-episode psychosis. Arch Gen Psychiatry 2005 Apr;62(4):361-70.

(6) Dorph-Petersen KA, Pierri JN, Perel JM, Sun Z, Sampson AR, Lewis DA. The influence of chronic exposure to antipsychotic medications on brain size before and after tissue fixation: a comparison of haloperidol and olanzapine in macaque monkeys. Neuropsychopharmacology 2005 Sep;30(9):1649-61.

(7) Andreasen NC, Nopoulos P, Magnotta V, Pierson R, Ziebell S, Ho BC. Progressive brain change in schizophrenia: a prospective longitudinal study of first-episode schizophrenia. Biol Psychiatry 2011 Oct 1;70(7):672-9.

(8) Molina V, Sanz J, Benito C, Palomo T. Direct association between orbitofrontal atrophy and the response of psychotic symptoms to olanzapine in schizophrenia. Int Clin Psychopharmacol 2004 Jul;19(4):221-8.

(9) Andreasen NC, Liu D, Ziebell S, Vora A, Ho BC. Relapse duration, treatment intensity, and brain tissue loss in schizophrenia: a prospective longitudinal MRI study. Am J Psychiatry 2013 Jun 1;170(6):609-15.

(10) Zipursky RB, Reilly TJ, Murray RM. The Myth of Schizophrenia as a Progressive Brain Disease. Schizophr Bull 2012 Dec 7.

(11) Fusar-Poli P, Smieskova R, Kempton MJ, Ho BC, Andreasen NC, Borgwardt S. Progressive brain changes in schizophrenia related to antipsychotic treatment? A meta-analysis of longitudinal mri studies. Neurosci Biobehav Rev 2013 Jun 13.

(12) Moncrieff J. Why is it so difficult to stop psychiatric drug treatment? It may be nothing to do with the original problem. Med Hypotheses 2006;67(3):517-23.

Thank You MIA and Dr Moncrieff.

"Obviously it sounds frightening and worrying, but the first thing to stress is that the reductions in brain volume that are detected in these MRI studies are small, and it is not certain that changes of this sort have any functional implications."

So are the Reductions in Brain Volume that can be detected from being hit in the head with a Baseball Bat.

http://psychroaches.blogspot.com/search?q=18C95


Evidence For The Neurotoxicity Of Antipsychotic Drugs, Dr Grace Jackson