Antipsychotic Drugs and Brain Shrinkage

Over the 40 years that I practiced medicine, I slowly became aware of the fact that drugs that cross the blood-brain barrier and thus impact the brain, especially those marketed for so-called mental illnesses (of unknown etiology), only mask symptoms and never cure anything - despite what the attractive, trinket-bearing salespersons from Big Pharma proclaimed as they were trying to convince me to prescribe their latest over-priced drugs (while at the same time abandoning the tried and true cheaper generics I had been using successfully for years).

When I went to medical school, we were taught that the relatively few psychiatric drugs available in the decade of the 1960s were too dangerous for us lowly family practitioners to prescribe safely. However, sometime between then and the generation of the 1980s, Big Pharma started flexing its Big Business muscles, started having previously restricted drugs available over-the-counter, started ignoring the psychiatrists (who coveted the monopoly they had had on psych meds), and started marketing heavily those same dangerous drugs so that we lowly family practitioners would help them increase their “market share”.
Living in a rural area where there were no psychiatrists to make wholesale diagnoses of mental illnesses (of “unknown etiology”) that supposedly warranted life-long drugging, I wasn’t asked by very many of my patients for psych drug treatment. But then came along Prozac.

The one time that I was asked by a patient to prescribe Prozac for her (a so-called selective [a lie] serotonin reuptake inhibitor [SSRI]), I was totally unaware that I had been deceived by Eli Lilly’s commercials and its drug reps when I was told how Prozac was supposed to work. They also skipped over (or were ignorant of) what were the serious potential dangers of the drug, especially the long-term dangers which included suicide, homicide, addiction, brain damage, sleep disorders, mania, psychosis, dementia, permanent sexual dysfunction, etc, etc. That patient didn’t take her Prozac for more than two weeks before it pooped out. But it got me curious about what synthetic, fluorinated, amphetamine-based chemicals like the SSRIs can do to the brain.
Lilly’s drug reps never tried to detail me on their so-called second-generation anti-psychotic drug Zyprexa, but by the time those drugs were being promoted, I was highly suspicious of Big Pharma and all of their mis-represented psych drugs. I had begun to understand why all anti-psychotic drugs were called “chemical restraints”, “chemical strait jackets”, “chemical lobotomies” or “zombification drugs”.

So when I ran across the following article (written by Dr Joanna Moncrieff, a British psychiatrist), about the most serious unintended long-term adverse effect (brain shrinkage!) of antipsychotic drugs, I decided to print extended excerpts of it below. I have done minimal editing. Phrases in italics are mine.

(The antipsychotic drugs that Dr Moncrieff is referring to include Thorazine (GlaxoSmithKline), haloperidol (generic), Abilify (Bristol-Myers Squibb), Clozaril (Novartis), Fanapt (Novartis), Geodon (Pfizer), Invega (Janssen), Resperdal (Janssen), Saphris (Merck), Seroquel (AstraZeneca), and Zyprexa (olanzapine - Lilly).

Antipsychotic Drugs and Brain Shrinkage

By Joanna Moncrieff, MD / December 13, 2013

Posted (including cited references)
at: http://joannamoncrieff.com/2013/12/13/antipsychotics-and-brain-shrinkage-an-update/

“After 18 months of treatment monkeys treated with olanzapine or haloperidol, at doses equivalent to those used in humans, had approximately 10% lighter brains that those treated with a placebo.” – Joanna Moncrieff, MD

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 honored 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 (and therefore with significant conflicts of interest), 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… 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 shrinkage in people diagnosed with schizophrenia or psychosis. This led to the (erroneous) 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 (and erroneously) described.… as a neurodegenerative condition (2).

The trouble with this interpretation was that all the patients 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 studies (and older 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 drug 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 Joseph Lieberman who headed up the CATIE study, published the largest scanning study up to that point of patients with a first episode of psychosis or schizophrenia (5). The study was funded by Eli Lilly, and consisted of a randomized comparison of Lilly’s drug olanzapine (Zyprexa) and the older drug haloperidol (Haldol). Patients were scanned at the start of the study, at 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. 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 author’s 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-, but 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 compare the effects of olanzapine and haloperidol in macaque monkeys. This study proved beyond reasonable doubt that both antipsychotics cause brain shrinkage. After (only)18 months of treatment monkeys treated with olanzapine or haloperidol, at doses equivalent to those used in humans, had approximately 10% lighter brains (at autopsy) than those treated with  a placebo (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 (7). Andreasen’s 2011 paper was widely publicized however, and it started to be 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 (rather than the now established fact that the drugs were causing the treated brain to shrink). In this paper there was barely a mention of the effects of antipsychotics that were revealed in the group’s earlier paper (8). What the authors did in the second paper was to assume that any shrinkage that could not be accounted for by the… antipsychotic effects must be attributable to the underlying disease. 

…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 any part of the observed effect is not drug-induced.

The latest paper by this research group replicates the findings on antipsychotic-induced brain shrinkage, but also (falsely) claims that brain volume reduction is related to having a ‘relapse’ (10).… 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 has found strong evidence of an antipsychotic induced effect, which they have replicated in two analyses now….

These researchers seem determined to prove (falsely) that ‘schizophrenia’ causes brain shrinkage… Their recent analysis once again confirms the damaging effects of antipsychotics, but the authors largely discount the effects of drug treatment and conclude that patients must not stop their antipsychotics. The only concession made to the antipsychotic-induced changes the study reveals 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 (11). 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 (12).

What should antipsychotic users and their families and caregivers 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, and their utility 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 can be associated with coming off these drugs (13). 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 labelled 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.

 This blog is a slightly revised version of one that appeared on Mad in America in June 2013.

Dr. Moncrieff is a Senior Lecturer in psychiatry at University College London and a practicing consultant psychiatrist. She has written three books: “The Bitterest Pills”, “The Myth of the Chemical Cure” and “A Straight Talking Introduction to Psychiatric Drugs”.  

Dr Moncrieff is also the author of a very useful article that has been posted at http://www.madinamerica.com/2015/02/need-know-starting-drug-mental-health-problem/. It is entitled “What You Need to Know Before Starting a Drug for a Mental Health Problem”. My advice is that everybody should read it, even if you are not destined to receive a prescription for such a drug.