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

Finnish Study Slams Seroquel, Risperdal, Zyprexa

But Before you Celebrate, The new Study from Finland is advocating Clozaril as the 1st Line Replacement for the Atypicals Seroquel, Risperdal & Zyprexa, ..... So the $64,000 question remains, Who, funded this study.

REUTERS has:

Study May Prompt Rethink On Schizophrenia Drugs

By Ben Hirschler

LONDON (Reuters) - Schizophrenia patients given a cheap older drug are less likely to die prematurely than people on newer treatments, despite the older product's well-known adverse side effects, Finnish researchers said on Monday.

The finding may lead to wider use of clozapine -- sold by Novartis as Clozaril, but also available as a generic -- instead of newer drugs like AstraZeneca's Seroquel, the current market leader.

Clozapine was the first of a new generation of schizophrenia drugs, known as atypical antipsychotics, but its use has been restricted by health authorities because of safety concerns, and patients taking it require regular blood tests.

Despite this, an analysis of 10 years' records for 67,000 patients in Finland found that, compared with treatment with the first-generation drug perphenazine, the risk of early death for patients on clozapine was reduced by 26 percent.

By contrast, mortality risk was 41 percent higher for those on Seroquel, known chemically as quetiapine; 34 percent higher with Johnson & Johnson's Risperdal, or resperidone; and 13 percent higher with Eli Lilly's Zyprexa, or olanzapine.

"We know that clozapine has the highest efficacy of all the antipsychotics and it is now clear, after all, that it is not that risky or dangerous a treatment," study leader Jari Tiihonen of the University of Kuopio said in a telephone interview.

"We should consider whether clozapine should be used as a first-line treatment option."

THOUSANDS OF PREMATURE DEATHS

Tiihonen estimates clozapine is given to around one fifth of Finnish schizophrenia patients, but less than 5 percent in the United States.

Clozapine's side effects include agranulocytosis, a potentially fatal decline in white blood cells, and current rules stipulate the drug can only be used after two unsuccessful trials with other antipsychotics.

Tiihonen and colleagues wrote in the Lancet medical journal that these restrictions should be reassessed in the light of their findings, since not using the drug may have caused thousands of premature deaths worldwide.

But Les Iversen, a professor of pharmacology at the University of Oxford in Britain, who wasn't involved in the study, said the risk of agranulocytosis was serious and should not be under estimated.

"For this reason, clozapine has become a drug of last resort -- and will probably remain so," he said.

Seroquel, Zyprexa and Risperdal are among the world's top-selling drugs, with combined sales of $12.5 billion in 2008, though Risperdal now faces generic competition.

Worries about the safety profile of all the atypical antipsychotics have loomed large since 2002, however, following evidence of increased rates of diabetes and cardiovascular disease.

The Finnish study found no pronounced differences in heart deaths between the different atypicals, but patients on clozapine had a substantially lower risk of suicide, while those on Seroquel were more likely to kill themselves.

An AstraZeneca spokeswoman said the Anglo-Swedish company was comfortable that Seroquel was safe, effective and an important treatment for mental illness.

Schizophrenia is a severe psychiatric disorder in which patients experience distorted thinking, hallucinations and abnormal emotions.

(Editing by Jon Loades-Carter/Will Waterman)

Soulful Sepulcher Has The Post You Must Read

Soulful Sepulcher has the 1 post we wish could be The Final Word on the subject.

But it won't.

8 Million Americans have already been Labeled.

The Mental Health Industry has Openly Targeted 60 Million for Labeling and Drug Treatment.

Advice From a Schizophrenic To My Daughter: Antipsychotics Don't Work

Stephany's Daughter was no different from Your 13 year old daughter before some Dr started her on an antipsychotic. She was NOT 'Mentally Ill'. The Mental Health Drugs Did this to her.

The Mental Health Industry itself would collapse tomorrow without Public, Govt Funding.

Single Payer Health Care will Only provide MORE of THE SAME.

Psychiatry Has it In The Pipe, even Further Expanding their Codex Of BS Billing Codes: Shrouded In Secrecy.

See Doug Bremner at Before You Take That Pill, for:

DSM-V Shadow Team: Retaliations & Beware Of Consequences

Mental Health: Comes With FREE Sudden DEATH

There's a New Medicine in town, and it's name is Fanapt: but First:

All 23 of the Psychiatric Poisons in our FDA Adverse Reaction section feature Sudden Death as an FDA reported Adverse Reaction with each Drug Individually identified as 'The Primary Suspect Drug' responsible for that Adverse Reaction

Abilify: Sudden Cardiac Death, Sudden Death
Adderall: Sudden Cardiac Death, Sudden Death
Celexa: Sudden Cardiac Death, Sudden Death, Sudden Infant Death Syndrome
Clozapine: Sudden Cardiac Death, Sudden Death
Cymbalta: Sudden Death
Depakote: Sudden Death
Effexor: Sudden Cardiac Death, Sudden Death
Geodon: Sudden Cardiac Death, Sudden Death
Klonopin: Sudden Death
Lamactil: Sudden Cardiac Death, Sudden Death, Sudden Infant Death Syndrome, Sudden Unexplained Death In Epilepsy
Lexapro: Sudden Cardiac Death, Sudden Death
Neurontin: Sudden Cardiac Death, Sudden Death
Paxil: Sudden Cardiac Death, Sudden Death
Prozac: Sudden Cardiac Death, Sudden Death
Risperdal: Sudden Cardiac Death, Sudden Death, Sudden Unexplained Death In Epilepsy
Ritalin/Concerta: Sudden Cardiac Death, Sudden Death
Seroquel: Sudden Cardiac Death, Sudden Death
Strattera: Sudden Death
Tegretol: Sudden Death
Wellbutrin: Sudden Death, Sudden Infant Death Syndrome
Xanax: Sudden Death
Zoloft: Sudden Death
Zyprexa: Sudden Cardiac Death, Sudden Death


It's FDA Label Time, for the Atypical Antipsychotics.

08/14/2008 Abilify pg 53

The mechanism of action of aripiprazole, as with other drugs having efficacy in Schizophrenia, Bipolar Disorder, Major Depressive Disorder, and agitation associated with Schizophrenia or Bipolar Disorder, is unknown. However, it has been proposed that the efficacy of aripiprazole is mediated through a combination of partial agonist activity at D2 and 5-HT1A receptors and antagonist activity at 5-HT2A receptors. Actions at receptors other than D2, 5-HT1A, and 5-HT2A may explain some of the other clinical effects of aripiprazole (eg, the orthostatic hypotension observed with aripiprazole may be explained by its antagonist activity at adrenergic alpha1 receptors).



0:26 "Call your Doctor if you have," ..... the Ability remaining to even Reach for the phone.

10/02/2007 Geodon pg 2

The mechanism of action of ziprasidone, as with other drugs having efficacy in schizophrenia, is unknown. However, it has been proposed that this drug’s efficacy in schizophrenia is mediated through a combination of dopamine type 2 (D2) and serotonin type 2 (5HT2) antagonism. As with other drugs having efficacy in bipolar disorder, the mechanism of action of ziprasidone in bipolar disorder is unknown.

05/13/2008 Seroquel pg 34

The mechanism of action of SEROQUEL, as with other drugs having efficacy in the treatment of schizophrenia and bipolar disorder, is unknown. However, it has been proposed that the efficacy of SEROQUEL in schizophrenia and its mood stabilizing properties in bipolar depression and mania are mediated through a combination of dopamine type 2 (D2) and serotonin type 2 (5HT2) antagonism. Antagonism at receptors other than dopamine and 5HT2 with similar receptor affinities may explain some of the other effects of SEROQUEL.

08/22/2007 Risperdal pg 36

The mechanism of action of RISPERDAL®, as with other drugs used to treat schizophrenia, is unknown. However, it has been proposed that the drug's therapeutic activity in schizophrenia is mediated through a combination of dopamine Type 2 (D2) and serotonin Type 2 (5HT2) receptor antagonism.

03/19/2009 Zyprexa pg 24

The mechanism of action of olanzapine, as with other drugs having efficacy in Schizophrenia, is unknown. However, it has been proposed that this drug’s efficacy in Schizophrenia is mediated through a combination of dopamine and serotonin type 2 (5HT2) antagonism. The mechanism of action of olanzapine in the treatment of acute manic or mixed episodes associated with Bipolar I Disorder is unknown.

So long as we let Govt keep Funding Old "D2/5HT2 Imbalance" here, Psychiatry is Going to keep Beating it,


and Promising that their "Mechanism of Action is Unknown" is going to get up yet, and Incurably Bio-$cience the whole damn Kentucky Derby, ..... someday. So Send More Money. They're short 2 bats.

But Wait! A Brand New MEDICINE, Unlike Anything Seen Before, is being Rushed to America's aid, thanks to our tireless PDUFA-crats at FDA.

FDA Approves Vanda Pharmaceuticals Fanapt

"Fanapt^™ is a mixed dopamine D2 / serotonin 5HT2A receptor antagonist, and belongs to the class of atypical antipsychotics."

And let's not Forget, in case the Other Atypicals don't work, and you somehow miraculously manage to Live through them:

06/29/2005 Clozaril pg 3

CLOZARIL® (clozapine) is classified as an ‘atypical’ antipsychotic drug because its profile of binding to dopamine receptors and its effects on various dopamine mediated behaviors differ from those exhibited by more typical antipsychotic drug products. In particular, although CLOZARIL does interfere with the binding of dopamine at D1, D2, D3 and D5 receptors, and has a high affinity for the D4 receptor, it does not induce catalepsy nor inhibit apomorphine-induced stereotypy. This evidence, consistent with the view that CLOZARIL is preferentially more active at limbic than at striatal dopamine receptors, may explain the relative freedom of CLOZARIL from extrapyramidal side effects.

All will be well. Trust in the System. Just SEND MORE MONEY. (Reuters)

T&A Wins The Day/Antipsychotics Chew Brains Away

Corpwatch US has:

Gimme An RX! Cheerleaders Pep Up Drug Sales

The Bitter Pill has Dr Fred Baughman on:

A Govt In Charge Of Your "Mental Health" Is Not A Democracy

Dr Bonkers has:

Graymatter

And:

Psych Quotes.com has:

"The reduction of intelligence is an important factor in the curative process… The fact is that some of the very best cures that one gets are in those individuals whom one reduces almost to amentia (feeble-mindedness)…"

Dr. Abraham Myerson, Harvard Psychiatrist, 1942

"We can choose to use our growing knowledge to enslave people in ways never dreamed of before, depersonalizing them, controlling them by means so carefully selected that they will perhaps never be aware of their loss of personhood."

Carl R. Rodgers, Former President of the American Psychological Association (APA)

"The techniques of brainwashing developed in totalitarian countries are routinely used in psychological conditioning programs imposed on school children. These include emotional shock and desensitization, psychological isolation from sources of support, stripping away defenses, manipulative cross-examination of the individual’s underlying moral values by psychological rather than rational means. These techniques are not confined to separate courses or programs...they are not isolated idiosyncracies of particular teachers. They are products of numerous books and other educational materials in programs packaged by organizations that sell such curricula to administrators and teach the techniques to teachers. Some packages even include instructions on how to deal with parents and others who object. Stripping away psychological defenses can be done through assignments to keep diaries to be discussed in group sessions, and through role-playing assignments, both techniques used in the original brainwashing programs in China under Mao."

Thomas Sowell, writing in Forbes, 1991

"Nearly half a century has passed since Watson proclaimed his manifesto. Today, apart from a few minor reservations, the vast majority of psychologists, both in this country and in America, still follow his lead. The result, as a cynical onlooker might be tempted to say, is that psychology, having first bargained away its soul (1) and then gone out of its mind (2), seems now, as it faces an untimely end, to have lost all consciousness." (3)

Sir Cyril Burt in British Journal of Psychology, Vol. 53, No. 3, 1962, p. 229.




"Don't Call Me A Journalist. I'm A Reporter. I Go Where The Stink Is."

Matt Drudge