Different Antipsychotics Have Different Effects on Brain Volume


First generation antipsychotics seem to cause general brain volume loss, while second generation antipsychotics seem to both increase and decrease the thickness of different parts of the brain, according to a study led by University of Melbourne researchers published in Psychological Medicine. And the effects on the brain, they found, are noticeable within a matter of months of beginning to take the medications.

Participants in the research were drawn from a cohort of 162 first-episode patients diagnosed with schizophrenia or affective psychosis who’d been taking antipsychotics for about three months, and 87 controls, who were involved in the Early Psychosis Prevention and Intervention Centre study between 1994 and 1999.

The researchers found that the participants’ diagnosis or type of illness did not have any predictive effects on the amount or kind of brain volume changes. These findings were in line with other studies; however, unlike other studies, the researchers found differences between how the first-generation (FGAs) and second-generation antipsychotics (SGAs) were changing the brain.

“Analysis of each treatment group compared with controls demonstrated that FGAs were associated with decreased thickness in frontal regions, whereas SGAs were associated with increased thickness of pre- and postcentral gyri in addition to decreased thickness of medial frontal, parietal and fusiform areas,” the researchers stated.

“Our results suggest that FGA and SGA treatments have divergent effects on cortical thickness during the first episode of psychosis that are independent from changes due to illness,” they concluded. The researchers then suggested that the elements of brain thickening caused by second generation antipsychotics “may have positive benefits on symptoms.”

(Abstract) (Full text) Divergent effects of first-generation and second-generation antipsychotics on cortical thickness in first-episode psychosis (Ansell, B. et al. Psychological Medicine. February 2015. DOI: http://dx.doi.org/10.1017/S0033291714001652)


  1. Bah. This study sounds like promotion for “second generation antipsychotics” more than anything else. There are lots of differences in receptor affinities between among “first” and “second” generation neuroleptics. This is what they actually did:

    “The final sample used in this study comprised 25 FGA-treated subject .. who were admitted between 1994 and 1996 (except five who were admitted between 1997 and 1998( and 27 SGA-treated subjects … who were admitted between 1997 and 1999. Importantly, patients were all treated within the same first-episode service and hence the time difference reflected anti-psychotic prescription guidelines at the time the date were collected. This reduced the possibility of drug prescription on the basis of demographic (e.g. age, gender or intelligence) or symptom (e.g. diagnosis and specific symptoms) that may have biased the results.”

    Earlier psychiatrists were telling patients and other psychiatrists that they’ve seen brain shrinkage in schizophrenia, and then add that it’s seen even before patients have been given neuroleptic drugs. Some often added that the “second generation” neuroleptic have been shown to reverse this process in some studies. Now, after those long term studies from Andreasen and so on, they are trying to publish studies which admit that those crappy “first generation” neuroleptics apparently have these crappy effects, but our new, on patent (at least in depot version) actually improve the brain.

    Also, for instance, Andreasen studies have been over a decade, these talk about “differences seen in months”, and so on.

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    • They admit in the final part that ” the simplified FGA/SGA dichotomy in this study belies the pharmacological complexity of each drug “, basically saying “yeah we know that lumping all these different drugs together into only two categories is kinda stupid”

      I don’t know, what do these MRI scans really mean ? That it ‘may’ mean something ? If these drugs ‘may’ make you smarter, then maybe some of these researchers would be keen to see what it’s like to chown down on them for a while.

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      • “I don’t know, what do these MRI scans really mean ?”

        I don’t know either. But I guess it’s easy to pick up 25 patients who used FGAs and 27 who used SGAs, from those crazy years of 1990s! And it’s easy to make another argument to support SGAs, based on that data. What all factors might go wrong with this type of studies?

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        • Well yeah to me any mention of mental illness seems particularly irrelevant for this study. They’re talking about ‘first episode’ schizophrenia. I mean, what is that anyway ?

          A psychiatrist decided after one ‘psychotic episode’ that a person must be schizophrenic ? This distinction is so confidently made, and then further confident decisions are made like who to rule out.

          A cynical mind might think that this is really just experimentation on humans, they just want to see what the drugs do to a human brain and they need people to test them on.

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          • I would imagine there could still be some question about a person’s condition after a “first episode”. After a “second” “third” “fourth” etc. “episode” though, it must be nearing the time to write them off as certainly “sick”. Drugs, or no drugs, somebody has come back for more abuse.

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  2. Here another new study. “Brain Structure and Function in First-Episode Schizophrenia” http://archpsyc.jamanetwork.com/article.aspx?articleid=2089518

    “Significant cortical thinning was identified in the medicated patient group relative to the control group in prefrontal (mean reduction [MR], 0.27 mm; P < .001), temporal (MR, 0.34 mm; P = .02), parietal (MR, 0.21 mm; P = .001), and occipital (MR, 0.24 mm; P = .001) cortices. The unmedicated patient group showed no significant cortical thickness differences from the control group after clusterwise correction."

    "Conclusions and Relevance These findings highlight the complex relationship between antipsychotic treatment and the structural, functional, and behavioral deficits repeatedly identified in schizophrenia. Although short-term treatment with antipsychotics was associated with prefrontal cortical thinning, treatment was also associated with better cognitive control and increased prefrontal functional activity. This study adds important context to the growing literature on the effects of antipsychotics on the brain and suggests caution in interpreting neuroanatomical changes as being related to a potentially adverse effect on brain function."

    Earlier they were using the brain shrinkage argument as a tool to use drugs. Now some try to say, with these short term brain studies and reasoning, that maybe the brain shrinkage is actually a good thing to happen in a schizophrenia patient.

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  3. To give an example of “neural reasoning” done on this subject, I’ll give as an example a review done by our friend, Torrey.

    Studies of individuals with schizophrenia never treated with antipsychotic medications: a review.


    “A review of 65 studies of individuals with schizophrenia who had never been treated with antipsychotic medications indicates significant abnormalities in brain structure and function. Neurological and neuropsychological measures show the most consistent and largest group differences between those affected and normal controls. Measures of structural differences and cerebral metabolic function are significant but less impressive. Electrophysiological differences also are found, but most such studies are older and have methodological problems. The brain abnormalities implicate a variety of interrelated brain regions, primarily the medial temporal, prefrontal, thalamic, and basal ganglia areas. It is concluded that schizophrenia is a brain disease in the same sense that Parkinson’s disease and multiple sclerosis are, and that the brain abnormalities in schizophrenia are inherent in the disease process and not medication-related. The challenge for the future is to use the new molecular techniques to study these brain areas and elevate our understanding of schizophrenia’s etiology to the next level.”

    “It is concluded that schizophrenia is a brain disease in the same sense that Parkinson’s disease and multiple sclerosis are, and that the brain abnormalities in schizophrenia are inherent in the disease process and not medication-related. “

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    • Isn’t it true that children who are abused show the same brain abnormalities as schizophrenics, so isn’t this debunked that brain scans show damage caused by schizophrenia rather than a persons effects over a life time (including often times experiencing abuse as children)?

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      • I guess all kinds of chronic stress, bad diet or even malnutrition, bad habits, lack of social contacts or other “play”, abuse of drugs, etc, can cause brain changes too. People who subsequently get diagnosed with schizophrenia often fall to this group of people. I don’t think there’s any one single (genetic, etc) disease “schizophrenia” which then “causes” these brain differences.

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  4. Holy brain damaging, irreversible mess, Batman.. Any increase use or decrease ase caused by substance use is brain damage, signs of mutilation. http://www.obamasweapon.com/

    It is never a normal trait for brain to grow or decrease in size when this result is not due to active learning and daily functioning and living. Period. Drugs can also cause out of control reactions in the brain, resulting in misgrowths, and total structure changes that are abnormal and not beneficial, and not linked to any normal operation of the brain.

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    • Ask the researchers to prove the positive benefit, ie IQ point increases. Bet they can’t do it. They can’t even tell you with certainty that brqin growth wasn’t sign of serious injury, or that it led to any functional improvement. Also other studies showed that the drugs were causing severe damage, swelling of tissue, scar tissue build up, vein swelling, fluid build up, in addition to shrinkage and volume changes.. This includes second gen drugs like Zyprexa and first gen ones like Haldol.

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      • Another study shows that the schizophrenic patient treated without meds had a higher chance of obtaining a job, and was less disabled. See Ron Unger’s previous highlighting of that 20 year study on the site, I think from August.

        The study highlighted how the drugs prevented recovery and prevented symptom remission, as even users who d/c’d their drugs would show signs of improvement. Therefore the drugs are linked to inducing and keeping people’s symptoms going.

        The drugs are also linked to causing severe encephalopathy and dementia.

        Something tells me these studies are being conducted improperly that don’t show this. Probably because they are one sided and incomplete, and are riddenly with marketing propaganda ..

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  5. I am a mother….this is all so scary.the psychiatrists keep pushing and pushing the drugs. My favorite now is ‘we will put him on this drug so he can come off the drug he is no now’, but they are unable to do it…..the iatrogenic illness can keep getting worse and there is no one to talk with within the system we are trapped in.
    Why does the family and the person subjected to these atrocities have to continue to push the system to correct itself?
    It is a cruel system.

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  6. The reasoning is quite simple, actually. Antipsychotics are, by assumption, automatically good. Antipsychotics cause brain thickening, therefore, brain thickening must be good. If they also cause brain thinning, then brain thinning must be good. As long as antipsychotic drugs caused it to happen, it must be good, because we know how tremendously helpful antipsychotics are.

    Ipso facto, QED.

    —- Steve

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    • Exactly my point. No matter what structural of functional effect they find the conclusion is ” it is likely to explain positive effects of drugs”. Tell me about bias.

      Funny how the same brain thickening/thinning in autism or schizophrenia is a cause of disease.

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  7. The researchers found that the participants’ diagnosis or type of illness did not have any predictive effects on the amount or kind of brain volume changes.

    Anybody notice the number of studies that, completely ignoring psychiatric drugs, attribute brain changes to “disease”?

    Problems in living don’t cause structural brain change. Psychiatric drugs do that. The new drugs may change the brain in different ways than the old drugs, but they still change the brain. One has to wonder why these researchers have such a hard time making this connection.

    Uh, I know. Because it isn’t about health really, it’s about social control.

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  8. “The researchers then suggested that the elements of brain thickening caused by second generation antipsychotics “may have positive benefits on symptoms.” ”
    I love how they jump to that conclusion based on no evidence at all. Drugs affect the brain size. That’s all they can reasonably conclude.

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