Controversy: Brain damage caused by mania/psychosis or neuroleptics?

[Giovanni]

This is an interesting topic of discussion.  Some researches claim that untreated psychosis/mania causes permanent brain damage, while others claim that neuroleptics are to blame.

 

Research suggesting mania/psychosis causes brain damage

 

A Manic mood swings can destroy grey matter: This 2007 study is based on MRI images of 21 patients diagnosed with severe bipolar disorder. 

 

Medication affects: status unclear.

 

MRI Study of Bipolar Reveals Structural Differences:  UC San Diego ENIGMA-based study.  2,447 adults with bipolar disorder and 4,056 healthy controls.  Showed thinning of gray matter compared to healthy controls, especially in areas of inhibition and motivation.

 

Medication affects: "The findings also showed different brain signatures in patients who took lithium, anti-psychotics and anti-epileptic treatments. Lithium treatment was associated with less thinning of gray matter, which suggests a protective effect of this medication on the brain."

 

Study suggests bipolar disorder may cause progressive brain damage: 2003 study of "15 non-symptomatic male patients with familial bipolar I disorder to those of 20 healthy male comparison subjects".  Used proton magnetic resonance spectroscopy.  Hippocampus implicated.

 

Medication affects: status unclear.

Manic episodes are related to changes in frontal cortex: a longitudinal neuroimaging study of bipolar disorder 1: "We compared patients who had at least one manic episode between baseline and follow-up (Mania group, n = 13) with those who had no manic episodes (No-Mania group, n = 18). We used measures of cortical volume, thickness, and area to assess grey matter changes between baseline and follow-up."

 

Manic episodes associated with decreased cortical volume.

 

Medication affects: 

 

"Hence, the drug use was comparable among groups and time points except for antidepressant use. We compared the MRI outcome measures between No-Mania patients who changed antidepressant use over time and those who did not. [...] Symptoms and use of a specific medication might be related to the patients’ brain morphology, which in turn might be related to the incidence of mania. Hence, controlling for medication use might in fact disguise effects the authors are interested in to detect."

Effects of medication on neuroimaging findings in bipolar disorder: an updated review: 2012 Meta-analysis.  "The effects of psychotropic medications, when present, are predominantly normalizing and thus do not seem to provide an alternative explanation for differences in volume, white matter tracts, or BOLD signal between BD participants and healthy subjects"

 

Medication affects: "From the structural studies, the most robust finding (20/45 studies) was that lithium was associated with increased volumes in areas important for mood regulation, while antipsychotic agents and anticonvulsants were generally not."

 

Is psychosis toxic to the brain? : "First-episode psychosis (FEP) can result in a loss of up to 1% of total brain volume and up to 3% of cortical gray matter.4,5 When FEP goes untreated, approximately 10 to 12 cc of brain tissue—basically a tablespoon of cells and myelin—could be permanently damaged."

 

Effects of Antipsychotic Medication on Brain Structure in Patients With Major Depressive Disorder and Psychotic Features: "Eighty-eight participants (age range, 18-85 years) completed a baseline scan; 75 completed a follow-up scan, of which 72 (32 men and 40 women) were useable for final analyses. "

 

Medication affects: "In this secondary analysis of a randomized clinical trial, antipsychotic medication was shown to change brain structure. This information is important for prescribing in psychiatric conditions where alternatives are present. However, adverse effects of relapse on brain structure support antipsychotic treatment during active illness".

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".

 

Medication affects: " 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."

 

This study is by E. Fuller Torrey, so be warned.  

 

Research suggesting neuroleptics causes brain damage

 

The Effect of Antipsychotic Treatment on Cortical Gray Matter Changes in Schizophrenia: Does the Class Matter?: "Longitudinal magnetic resonance imaging studies comparing changes in the volume of cortical GM over time between patients with schizophrenia and healthy control subjects published between January 1, 1983, and March 31, 2014, were analyzed."

 

Medication affects:  "Over time, patients with schizophrenia showed a significantly higher loss of total cortical GM volume. This was related to cumulative antipsychotic intake during the interval between scans in the whole study sample. Subgroup meta-analyses of studies on patients treated with second-generation antipsychotics and first-generation antipsychotics revealed a different and contrasting moderating role of medication intake on cortical GM changes: more progressive GM loss correlated with higher mean daily antipsychotic intake in patients treated with at least one first-generation antipsychotic and less progressive GM loss with higher mean daily antipsychotic intake in patients treated only with second-generation antipsychotics."

Long-term Antipsychotic Treatment and Brain Volumes: "Two hundred eleven patients with schizophrenia who underwent repeated neuroimaging beginning soon after illness onset, yielding a total of 674 high-resolution magnetic resonance scans."

 

Medication affects: "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."

Normalizing the Abnormal: Do Antipsychotic Drugs Push the Cortex Into an Unsustainable Metabolic Envelope?: Article exploring neuroleptics and brain metabolism.

 

Medication affects: "Their long-term use is, however, associated with side effects, including several types of movement (extrapyramidal syndrome, dyskinesia, akathisia), metabolic and cardiac disorders. Furthermore, higher lifetime antipsychotic dose-years may be associated with poorer cognitive performance and blunted affect, although the mechanisms driving the latter associations are not well understood"

Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium: This is the ENIGMA data set again.

 

Medication affects: "Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers."

 

My take?

 

Neuroleptics alter the brain, though the brain is a plastic organ and may recover in period of years.  The key debate is whether untreated mania/psychosis also alters the brain, and neuroleptics on balance are neuroprotective. 

 

Mania/psychosis is often associated with severely disturbed sleep and metabolic patterns (check my thread if you don't believe me), and it makes sense that damages the brain over time.   

 

The ENIGMA data set is probably the best on the subject.  

 

Lithium seems safer than neuroleptics for those in mania, though the distinction between mania and psychosis is quite blurry (I guess delusions/hallucinations are the key distinguishing factor).

 

Obviously, neuroleptics cause harm.  So does mania/psychosis. 

 

Can we get people out of mania/psychosis without neuroleptics? 

 

Soteria/OpenDialogue is promising, but for those who were put on neuroleptics before hand, the rebound psychosis/mania can be devastating.  

 

I'm curious about everyone's opinions on the subject, especially those who have managed to control manic and psychotic symptoms without medications.

 

[Joey805]

Background: I'm currently tapering from Seroquel and Depakote after around one year of being prescribed these antipsychotic drugs. Last year I was hospitalized for a psychotic event which was characterized as a bipolar manic episode, although after working through this with my doctors we've concluded that I don't have bipolar and that the event was likely due to the extreme quantities of THC I was consuming through vaping high doses of concentrates.

 

So, I would first of all like to say that people dealing with psychosis and manic episodes should be extremely careful about the substances they ingest, even ones like THC (which my whole life had been touted as this super benign nothing-can-go-wrong fun thing). I've only had one such episode in my entire life and I don't have any sort of mood instability issues to speak of.

 

I'm extremely worried about the long-term effects of these medications and others I've been prescribed on my cognitive abilities and brain health. I feel like I'm slower than everyone else, less clever, with less access to my vocabulary and memory. I didn't used to be this way, but I think I am seeing improvements after reducing my dosages and paying closer attention to my sleep hygiene, caffeine intake, daily exercise, and nutrition.

 

Since I've only ever had the one psychotic event and it was immediately "treated," I can at least say in my case that the negative effects I'm experiencing are almost certainly from the antipsychotic medications. I worry that there are a lot of other people who have had "one off" psychotic events due to drug use or shirking on sleep who are now also being harmed by medication they don't actually need. I wonder about the number of patients taking antipsychotic medications who may have gone the rest of their lives without another event regardless.

[itiscomplicated]

On 10/4/2022 at 5:02 PM, Giovanni said:

I'm curious about everyone's opinions on the subject, especially those who have managed to control manic and psychotic symptoms without medications.

 

About controlling symptoms without medications - I may or may not have Bipolar II, but I sure never had delusions/psychosis/mania until I was on a combination of meds that caused it.

 

My guess would be that Lexapro and benzodiazepines played the biggest part in triggering delusions, and the character of all of it changed when I stopped the combination CT. Some of it was like mania delusions, some like anxiety delusions.

 

It took until 4-5 months after CT'ing the meds for me to realize that what had been going on starting more than a year and a half earlier had been mania and, later, delusions.

 

I still have some residual anxiety-based delusional thought patterns, 7 months later, but for me what worked for mania/psychosis was time, and reflecting back on and writing about what happened.

[Altostrata]

@Giovanni please do not post articles here without attribution -- where the article comes from, with the publication date and author.

 

Anybody can say anything on the Web. There is no evidence that brains with mood disorders or psychosis differ from "normal" brains. Effects of drugs on the brain and nervous system are not necessarily "damage", meaning lasting organic change.

 

Further, our brains and nervous systems change all the time and show a remarkable ability to adapt and heal via neuroplasticity.

 

So while this unsourced article may be "interesting", it contains no reason to alarm people here with its quasi-information.

[Giovanni]

Thanks for the tips, will do so in the future.

 

For future readers, I want to be absolutely clear about my opinion: the evidence that mania/psychosis is a result of brain damage or causes brain damage is weak, but pushed by proponents of mainstream psychiatry.  The best evidence (ENIGMA data) shows in fact neuro-leptics cause cortical changes. 

 

I just want to point out certain examples of FUD (fear, uncertainty, disinformation) that one may encounter on the Internet about this subject.  I encountered it myself (since my brother is unmediated now and sort-of psychotic - don't want him to be permanently brain-damaged!).

 

These examples include :

 

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Episodes cause brain damage, each time your SO experiences an episode, it hurts them. The worse the episode, the more damage internally. It actually causes a decrease in intelligence as well.

Help for all of the ones who have unmedicated partners.

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A study of over 6000 MRI scans of bipolar patients, called ENIGMA, showed loss of grey matter in the brain. Lithium seems to help combat it.

Bipolar can cause brain damage?

 

I know citing Reddit posts isn't great, but this is the type of information people encounter when considering options.  These opinions are based on poor reading of data. 

 

This needs to be debunked just like the serotonin hypothesis of depression, hence my post.

 

[Altostrata]

Everybody has opinions. Truth is a little harder to produce.

[Happy2Heal]

I will take issue with the idea that mania causes brain damage for this reason:  how is mania being diagnosed?? I have been diagnosed as having been "manic" when it was almost surely a reaction or side effect to the SSRI and other drugs I was on at the time.

 

you know the old  joke, see 3 psychiatrists get 4 different opinions! 

 

the fact is that diagnosis is at best an opinion with nothing concrete to back it up.  

 

When I was inpatient many years ago, in the 90s I think it was? , the staff was very pleased to go around and tell everyone that "new emerging evidence"

shows that each episode of mania and or other "mental illness" damages your brain if it's not treated with meds and eventually you will "Kindle"!!
that was my first time hearing the word kindle and it was in the context of the supposed illness I was told I had, being the cause of this kindling- where If I didn't accept the drug "treatment" my brain was going to be stuck in being permanently ill and no drug would help. Even a short period of being "un medicated" was dangerous to your brain!  be afraid, be very afraid!!

 

Give me a break. Even then I figured this was the drug company trying to push back over the growing evidence that the drugs don't "work", whatever that is supposed to entail.

 

~~~~~~~~~~~~~~~

as far as recommending lithium as a safe treatment for this supposed brain damage, how about the damage that lithium can do to your kidneys?

 

I was just diagnosed with drug induced nephrogenic diabetes insipidus. From lithium, from high doses, and I would imagine, from  having had a toxic level twice that needed emergency care, as well

 

NID from lithium  is often reversible to a certain extent but for most who took lithium for a long time and got kidney damage, it's not fully reversible. 

 

and it's not easily treated. My endo gave me something that might help, a little bit. But I consider myself lucky as some end up in kidney failure and my kidneys function well. I just have to get up almost every hour during the night to go to the bathroom and during the day always need to know where one is. It sucks but it could be worse.

 

 

I also have damage to my parathyroid gland, according to the endocrinologist, from the lithium.

 

There is still so little that is truly known about these drugs that are given out like candy and such a HUGE financial incentive to hide anything that proves or even hints at the damage they can do

 

We have to learn to be very wary of what those who can profit from their advice, tell us we need to do!!

 

 

 

 

 

Edited January 20, 2023 by Happy2Heal

[Giovanni]

UCSF biological psychiatrist Joe Pierre has a Twitter thread that asserts 2nd generation neuroleptics increase brain volume during first 3-months of psychosis.

He cites a Nature study, here:

 

https://pubmed.ncbi.nlm.nih.gov/15809403/

 

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Patients with first-episode psychosis exhibited a significant between-treatment difference in MRI volume changes. Haloperidol was associated with significant reductions in gray matter volume, whereas olanzapine was not. Post hoc analyses suggested that treatment effects on brain volume and psychopathology of schizophrenia may be associated. The differential treatment effects on brain morphology could be due to haloperidol-associated toxicity or greater therapeutic effects of olanzapine

 

However, at 12-months, the brain volumes of even the 2nd generation neuroleptic psychosis group and the neuroleptic naive psychosis group were the same.  Also, when taking into account longer term data (like the ENIGMA data), it's clear even 2nd generation neuroleptics cause brain changes during administration. 

 

That's why some claim lithium is "neuroprotective" for bipolar patients.  Probably a corollary is true: lithium doesn't affect the brain as much as neuroleptics, but does cause damage in other areas (i.e, kidneys)  

 

Some researchers have observed potentially protective changes in the brain during psychosis, independent of medication.  I wonder how much of that affect is related to the patient's psycho-social environment during initial psychotic breaks?

 

Quote

 

The study, led by Dr. Lena Palaniyappan, psychiatry professor and scientist at Robarts Research Institute, showed brain tissue actually increases in certain areas in patients with psychosis—even before they receive treatment.

 

This could indicate that the brain’s attempts to rebuild itself may start even before a patient receives medical , Palaniyappan said.

 

 

https://neurosciencenews.com/psychosis-brain-20078/

 

There's also another study that also indicates compensatory changes lead to decreased "mental illness".

 

Biological psychiatrists remind me of the blind men touching the elephant.  Of course, psychosis is a powerful experience, and that may manifest itself in brain imaging.  People have brain-imaged London Taxi Drivers and found differences between controls.  You can probably find brain-imaging differences between a post-withdrawal brain and brain on neuroleptics.

 

The problem with these neuroimaging studies is they are just a waste of money and time that won't reach any useful therapeutic endpoint.  They take away public money to fund the wild goose chases of academic researchers.  Despite so much research, mental health in industrialized societies is worse than ever.

 

After thousands of MRIs, the biologic psychiatrist will likely reach the same conclusion holistic/tribal practitioners reached decades/millennium again:  social support and time to recover in a safe place are crucial to resolving psychotic symptoms. 

 

The hope that these brain imaging studies will lead to a single compound that enables recovery is far-fetched.  The brain is too complicated for that.  

[Happy2Heal]

2 hours ago, Giovanni said:

After thousands of MRIs, the biologic psychiatrist will likely reach the same conclusion holistic/tribal practitioners reached decades/millennium again:  social support and time to recover in a safe place are crucial to resolving psychotic symptoms. 

 

The hope that these brain imaging studies will lead to a single compound that enables recovery is far-fetched.  The brain is too complicated for that.  

 

 

yup but you can't make a job out of recommending those common sense things. Psychiatry is pseudoscience at BEST...

it's sickening how much time, effort and money is wasted on it trying to legitimize itself.

 

thanks for your post

[Altostrata]

Joe Pierre's specialty is inpatient treatment of psychosis and his career has been working for the Veteran's Administration. Do you think he might have a vested interest in seeing antipsychotics as more beneficial and less harmful?

[Giovanni]

More 'research' coming out from Monash University, implying psychosis is neurodegenerative disease:

 

Quote

 

Now Monash University researchers have modelled how the effects of psychosis spread through the brain, allowing them to isolate areas where these changes may originate and which could be targeted by therapies designed to reduce the disease’s progression.

 

The study, published today in the prestigious Journal of the American Medical Association Psychiatry, details how the scientists were able to map and model the spread of brain changes in people with different stages of psychoses such as schizophrenia, from people newly diagnosed to those who have experienced psychosis for years.

The study, led by  Dr Sid Chopra , from the Turner Institute for Brain and Mental Health and Monash University’s School of Psychological Sciences, identified the hippocampus, which is important for memory, as a possible early site of brain changes in psychosis.

 

“This finding could potentially guide therapies that can target this area of the brain, potentially limiting the impact of the illness or perhaps even reducing the risk of psychosis onset,” Dr Chopra said.

 

 

Claims to have differentiated between antipsychotic induced grey matter changes and ones which occur naturally.

 

Quote

 

The researchers used a mathematical model to predict grey matter volume changes in four different groups of people with schizophrenia, scanned at both early and late stages of illness.

 

According to Professor Alex Fornito, who led the research team, “we found consistent evidence that the hippocampus, an area important for memory and which is known to play an important role in schizophrenia, is a candidate epicentre of brain changes in the illness.”

 

Importantly the researchers were able to distinguish brain changes associated with disease from those linked to the use of antipsychotic medication. “Most research has taken place with people who are already taking antipsychotic medications, making it difficult to disentangle the effects of medication from those of illness,” said Dr Chopra.

“Our network-based model was able to account for both medication-related and illness-related brain changes, meaning that brain network architecture represents a fundamental constraint on both types of brain changes in psychosis.”

 

 

https://www.monash.edu/news/articles/scientists-reveal-how-the-effects-of-psychosis-spread-throughout-the-brain

 

I of course don't have the time nor energy to dig into their claims.  Plus, most of these articles are pay-walled anyways, adding barriers to citizen scientists.  But I will log it here for posterity, just to keep a historical record on the claims of these so-called researchers.