Antipsychotics Increase Risk of Dementia; New Research Illuminates Why

In JAMA psychiatry, researchers outline new theories connecting antipsychotic use in people with schizophrenia and increased dementia risk.

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In a new article in the top psychiatry journal, JAMA Psychiatry, researchers propose two theories to explain why people with schizophrenia are more likely to have dementia. Both theories place the blame on antipsychotic drugs. The first involves metabolic dysfunction caused by antipsychotic drugs; the second concerns the drugs’ direct effects on the brain.

“Antipsychotic exposure has been linked to worse cognition in both cross-sectional and longitudinal observational studies,” the researchers write. “These results have been confirmed in randomized clinical trials showing cognition improves when antipsychotic dosage is reduced.”

The researchers were Katherine Jonas, Anissa Abi-Dargham, and Roman Kotov, all at Stony Brook University.

According to the researchers, people with a schizophrenia diagnosis are up to 11 times more likely to have dementia than people without a “serious mental illness” diagnosis. They also note that people with schizophrenia are 5.2 times more likely to die of dementia than the general population. They’re also more likely to have dementia at an earlier age than in the general population. This was also found to be true for other psychotic diagnoses, like bipolar disorder.

So why are people with diagnoses like schizophrenia and bipolar disorder so much more likely to have dementia? The researchers write that antipsychotic drugs (also known as neuroleptic tranquilizers) could be the culprit, either by causing metabolic syndrome or by causing dysfunction in various brain pathways.

“Metabolic syndrome,” which includes obesity, high blood sugar, and high blood pressure, is linked to heart disease, diabetes, and stroke. It’s also been linked to dementia.

According to the researchers:

“People taking antipsychotic medications are nearly 8 times as likely to have metabolic syndrome compared with antipsychotic-naive patients, perhaps because antipsychotics can alter insulin and glucagon release directly by acting on dopamine receptors in the pancreas.”

Surprisingly, though, the researchers don’t suggest that people should discontinue or lower their dose of antipsychotics, instead simply recommending “a preventive, lifelong focus on cardiometabolic health.”

The researchers also suggest dopamine dysfunction as a potential pathway.

“Antipsychotics may contribute to dementia via modulation and degeneration of the mesocortical dopaminergic circuit, the same circuit underlying cognitive decline in dementia and Parkinson’s disease,” they write.

The impact of antipsychotics on this system (and others) also explains the high rates of drug-induced parkinsonism and movement disorders (such as tardive dyskinesia) in people who take the drugs. These adverse effects are incredibly common even with newer antipsychotics.

The researchers note that antipsychotics have also been found to cause cortical thinning and loss of gray matter and that studies have concluded that this is not due to the underlying “illness” but to the drug’s impact on the brain.

“This association is not explained by illness duration or symptom severity, suggesting that antipsychotic exposure itself drives cortical loss,” they write.

The authors also propose another dementia pathway, which involves the anticholinergic effects of the drugs. They write:

“Anticholinergics have been shown to double dementia risk in the general population and are associated with cognitive impairment in schizophrenia.”

The researchers make it clear that these pathways are not exclusive. Instead, it is likely that all of these effects combine to create an eightfold higher risk of dementia in people who take antipsychotics.

In their conclusion, the authors call for more research on this issue.

 

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Jonas, K., Abi-Dargham, A., & Kotov, R. (2021). Two hypotheses on the high incidence of dementia in psychotic disorders. JAMA Psychiatry. Published online September 15, 2021. doi:10.1001/jamapsychiatry.2021.2584 (Link)

10 COMMENTS

  1. “The researchers write that antipsychotic drugs (also known as neuroleptic tranquilizers) could be the culprit, either by causing metabolic syndrome or by causing dysfunction in various brain pathways.”

    I’m quite certain the neuroleptics do both. Plus, they can make a person “psychotic” – a “positive” symptom of “schizophrenia” – via anticholinergic toxidrome poisoning.

    https://en.wikipedia.org/wiki/Toxidrome

    “Anticholinergics have been shown to double dementia risk in the general population and are associated with cognitive impairment in schizophrenia.”

    And both the antidepressants and the antipsychotics are anticholinergic drugs.

    Thank you for sharing my psychopharmacological research finding, Peter. Since we apparently live in a staggeringly paternalistic society, where psychiatrists believe a woman’s entire life is a “credible fictional story,” thus nothing we say is taken seriously. Thank you for hearing me, and repeatedly reporting on this very important finding, Peter.

    And at least us “irrelevant to reality,” “w/o work, content, and talent,” (based upon gossip from some child abusers, according to my therapist’s and child’s medical records), and us “one in a million” medical researchers (according to the head of family medicine at the Cleveland Clinic) can assist in pointing out the iatrogenic etiology of the “sacred symbol of psychiatry.” The neuroleptics can also create the negative symptoms of “schizophrenia,” via neuroleptic induced deficit syndrome.

    https://en.wikipedia.org/wiki/Neuroleptic-induced_deficit_syndrome

    And just an FYI, to anyone out there who is asked “Are you depressed,” for no apparent reason, in a hospital. If you say no, and mention you’re allergic to the anticholinergic drugs, the “Dr. Paines” will run away quickly.

  2. I was on Adderall, Abilify, Seroquel, Zyprexa, Lamictal, and Vraylar at the same time since 2015. But my “forced intoxication” began at the age of nine 25+ years ago and needs further explanation. I was diagnosed with ADHD at age 9. Put on Ritalin and an antidepressant. By age 10, they diagnosed me with early-onset childhood Bipolar with psychosis and a seizure disorder. I was in and out of institutions over a dozen times the next 15 years. By my early twenties, five medications by age 30, six medications. Then 14 months ago, I had a bowel obstruction and was off all meds for seven days due to being NPO in the hospital.
    The doctors were baffled—no evidence of Bi-Polar, psychosis, or seizures. When I left the hospital, they put me on 6mg of only Vraylar. I have never been this stable!
    My family and I decided we needed a second opinion. My psychiatrist of 25 years said I have Bi-Polar and need the Vraylar for the rest of my life. My family and I disagreed and found a new holistic therapist.
    For four months, I’ve been tapering off the Vraylar, and again no mood problems or psychosis. I’ve not been on a therapeutic dose for two months. Another month I’ll be off Vraylar totally!
    I have worked full time the last six months and am getting off disability. I’ve been on disability for 20 years.
    I am concerned by the disturbing information in this article. Being on six psychotropic medications for over 20 years, do I need to be concerned about early-onset dementia? I had severe obesity, high blood pressure, high triglycerides, and cholesterol most of my life. Since getting off all these meds, I have lost 70 pounds in the last 14 months, and recent blood tests are normal. My new holistic therapist believes I was misdiagnosed and was never mentally ill with Bi-Polar in the first place. Thank you for reading my short story. I hope I can help and inspire others in the same boat.

    • Another psychiatric “success story!” It is always stunning to me how absolute proof that the drugs were doing DAMAGE, let alone not helping, does nothing to move them from believing you are crazy for stopping their wonderful drugs!

      Thanks for sharing your story, and well done for getting out of their clutches!

    • Stimulants and serotonin drugs cause “psychotic” and “manic” behaviors/feelings. Essentially psychiatry gave you drugs and then gave you more drugs to address the problems caused by the first drugs. And round and round it went.

      “Mental illness” is a misnomer in that a medical illness is defined as a biological abnormality that causes negative effects. There are no scientifically replicatable or valid biological abnormalities that cause what psychiatry calls “mental illness”. They don’t do any tests and instead utilize circular reasoning to declare someone ill and in need for deadly drugs for life.

      Your story is uncommon in that you recognized the drugs were not helping and that you were better without them. Many people struggle to find the courage to admit that. I hope you can see the strength that took from you.

      As for being concerned about negative health outcomes in the future you will have increased risk but that does not mean you will get dementia or have a heart attack. You will also have less risk because you are no longer taking the drugs and because your physical health has improved. The primary thing you can do now is stay off the drugs and work at having a healthy lifestyle.

  3. Once again, our Brave New World fails to embrace an opportunity to publicly recognize the unnecessary harm it inflicts on vulnerable populations:

    “Surprisingly, though, the researchers don’t suggest that people should discontinue or lower their dose of antipsychotics, instead simply recommending ‘a preventive, lifelong focus on cardiometabolic health.'”

    Instead of recommending known treatments that Do Not Harm people, these researchers chose to follow many others who would rather push the false narrative that psychiatric drugs are necessary. Any harm caused by the drugs is merely a new revenue stream for cardiometabolic health professionals.

    If our medical system is unwilling to admit the immense harm these drugs have caused many individuals, families, and society, where does this leave us?

    Does anyone know how to measure the loss of humanity — brilliance, creativity, human connections, COMMUNITY — we have lost due to the relentless harm inflicted on traumatized people who then had the misfortune of asking a poorly-guided medical professional for help?

    -Arthur

  4. I agree 100%.

    The antipsychotics are damaging many people, in my opinion. Though some do find them useful in the short term. I myself am thinking of selling my leftover pills to any countries that use bio weapons, so they can immobilize huge populations by giving them obesity in a matter of weeks. The funds could ostensibly pay for my dementia care. Jokes aside…

    I think no pill is a good pill.

    However, I am not in agreement with the notion that there is no such thing as mental illness.

    “The ill have a right to be ill!”

    If you have really awful depression you feel so dreadful that you tell people you “feel ill”. You are ill, ill, ill, with a sense of despair and hopelessness and distress. You feel too ill, ill, ill to want to live through another day.

    If someone who does not know the inner hellish experience of your mind then tells you you are not ill, how would you feel?

    You feel ill in your mind, which is to say, your mental compartment specifically. Your big toe is not ill. Your knee is not ill. Your heel is not ill. You are not phoning a suicide hotline to talk about your toe. Your mental self is what feels really ill. I do not think it is for anyone to judge the inner experience you have of your mind and whether it feels ill or not. And I do not think it is for anyone to judge causality of the “feeling ill” part unless that impression or advice is overtly asked for. A consultant is one who is c o n s u l t e d. A consultant should not be a dictator. The two words are different. It would be better to scrap the word consultant and replace it with
    a d v i s o r.

    Indeed scap the word activist and replace it with
    a d v i s o r.

    Indeed scap all the “know all” titles and replace them with the respectful term
    a d v i s o r.

    Titles lead to entitled. Entitled to proclaim who you are and who you are not, and entitled to proclaim what your psyche feels and what it does not.

    I am schizophrenic. I am not depressed. I am not in despair or hopeless. Yet I am ill. I feel ill. I understand perfectly what my ill feeling is. It is not my big toe. It is in my mental experiences. I am mentally ill with my schizophrenia. It is a real diagnosis that I make. I am a free person who can do so. No one can show me the bit of my mind or brain that does not have schizophrenia. Some might say it is coming from my big toe, just as some might tell someone who feels ill from depression that they need to clip their toe nail to feel better. Some may do so as a titled consultant. Some may do so as an activist. Some may do so with a genuine wish to offer advice, as in being an
    a d v i s o r.

    I am very much in favour of abolishing certain treatments that are clearly detrimental. The sooner the better.

    I am totally against the scandal of misdiagnosis and coercive treatment that have no merit and for which informed consent can only be dubious.

    I am totally against forced treatment.

    I am not going to say I do not have a mental illness.

    It gets as petty as when some people tell others they are born in the wrong body, some peole tell others they are not born in the wrong body. What I mean is Nobody needs ANYONE…

    “telling them”

    the interior of their own being.

    This is a bolder mega message that the movement should endorse.

    What seems to be going on instead is in the attempt to counter psychiatry by claiming everything in it is bogus, people are claiming that original reason why people went to get help from their psychiatrist is also a bogus reason, as if feeling ill with depression or suicidality or schizophrenic voices and hallucinations is bogus. It gets that you dare not say you are feeling ill with depression unless you “qualify” it by saying it got “given” to you by someone, such that it is no longer your depression at all but something done to you by a “them”, or that your mental illness is not yours at all. You no longer own your unique inner you, as if you no longer own your skin colour, or sex, or temperament. All these get carted of to be used by that regime or the next regime or the future regime.

    • It seems to me that you’re saying a person has a right to view him/herself as ill if he/she sees it that way. I don’t hear anyone arguing with you on this point. I think you may misunderstand that when someone says, “ADHD” is a bogus diagnosis, they don’t mean that no one acts or feels that way, just that labeling that set of behavior and calling it an “illness” is not a scientifically valid undertaking. I’m all for people identifying as they see fit, as long as they don’t do it for someone else. So for you to say you have an illness called schizophrenia is your right. For Doctor So-And-So to tell Mary that SHE has an illness called schizophrenia, despite his complete lack of ability to objectively tell her what that means, THAT is where the problem arises. Some (like you, apparently) don’t mind that label, and that’s all fine for them. But what of the person who doesn’t agree that s/he is “ill” by the DOCTOR’S definition? Where are their rights? By your philosophy, don’t they have a right to refuse that label put on them by a doctor without consultation or agreement?

      • It is all in the notion of rising above the two camps, where the one camp says…
        “I am ill and I want this be called my schizophrenia”
        and the other camp says…
        “I am not ill so do not call me anything”.
        Both camps have every right to be respected.
        Both camps have every right not to feel bullied or ridiculed or coerced into thinking they are wrong to want what they like.
        The world is VAST.
        It is perfectly fine for one person who feels ill and wants to call themselves schizophrenic to sit in a cafe with someone who is not feeling they themselves are ill.

        When each person on the planet can say their own preferences without being hounded for it in any place then the planet is back to normal. When even one person on the planet is frightened to air their preferences then the planet is not normal, it is infected with a contageon called bullying. A bully can stop someone who feels ill and who wants to name their illness. A bully can stop someone who does not feel ill and does not want a name for the illness they feel they do not have.
        A bully can be someone with personal lived experience of the illness. A bully can be a friend or colleague of someone with experience of the illness but they themselves may not know the illness from the interior. A bully can be someone with absolutely no experience of the illness. Just as a bully can be someone with lived experience of being black. A bully can be a friend or colleague of a black person but with no experience themselves of being black. A bully can be someone with absolutely no experierience of what it is like to be black. Or a migrant. Or a man. Or a homeless person. Or a woman.

        The key is the bullying. If you start by commiting to not bullying and not accepting being bullied, you set the planet on a path to normal. Bullying is NOT NORMAL.
        That is what makes the observance of bullying integral to ANY health restoration. Bullying is deeply important. Bullying is overlooked as if it is other things like…
        .logical argument.
        .for your own good.
        .just the way the system is.
        .defining you for effeciency.
        .putting you in your place.
        .part of what needs to occur to overthrow another group.
        .scientific assessment.
        .testing your allegience to a group.
        .shape your character.
        .make you sorry you are different.

        A bully often becomes a bully because that is all they know. A bully may have had their choices and preferences bullied out of them so they dont see why you should indulge in your own free choices. Bullying is endemic and causes suffering. Power is not the same thing as bullying. A nurse on a cancer ward can heal hundreds by using his power to make them better. Power is neutral force. But when power is lined up with bullying a form of tyranny can kick off.

        A psychiatrist is in a postion of power, much like the nurse. The psychiatrist may not be a bully.

        Alternatively a psychiatrist may take their power and slot it next to a tendency to bully and become a source of suffering to others. It is not that they have power, nor that they are a bully, but the combination. A two year old can be a bully in rare occasions but they are not in a position of power.
        In psychiatry the innordinate amounts of unchecked power have become a problem. And bullying has become a problem in that work.

        A therapist has less power. So even if a therapist were to be a bully it is not quite so catastrophic. A therapist will tend to ask you what you as an individual prefer as choices. Do you want to be known as someone with schizophrenia or not? If you say yes then there is no problem with honouring your free choice. The therapist is not pontificating over your choices. If you want to know yourself as a seahorse or a levetating time machine then that is fine. This is civilized. This is not bullying. This is not power.

        But in ANY relationship bullying and power will be beneath the surface on both sides of a discussion. Paying more attention to those is useful since the ability to notice bullying holds the promise of freedom from fear, since bullying is a fear response, a fear connected to an inability to “control” the mind of the other. A fear of letting go.

        A healthy debate welcomes many views and differences and tolerates outsiders. A system like psychiatry has not been welcoming. A bully cannot bear to be welcoming because they feel too much fear. A bully shuts down broad discussion and narrows the paradigm to only accepting a rigid standpoint. This then excludes anyone who cannot fit in the paradigm. When someone different tries to belong, they get sidelined and given a narrow definition…like trouble maker, or agitator, or slow learner, or enemy, or schizophrenic, or ADHD kid, or seahorse. None of these given descriptions may be wanted. Or maybe for some they actually are. The point is not the description. The point is do you like it or not. If you do not then do not accept being bullied into having it.
        I myself am not traumatized. I am not depressed. I am not hypnotized by psychiatry. I am not well. I am ill.I do not have a personality disorder. I am not a trouble maker. I am not a slow learner.

        I am suffering greatly from my schizophrenia. It may have been called a different thing in ancient history but this is what it is to me.

        What schizophrenia can be called is a distraction away from the urgent matter of how any one person feels entitled to bully.

        If humanity stops ALL FORMS OF BULLYING by anyone, for any reason, then it is the answer to EVERYONES prayers.

        Imagine you want to go to Nepal. But some tour guide says that you must not go to old temple shrine because its toxic, and you must not visit the lofty peak because it is not lofty at all, and you must not shine a torch on the moonlit river to see the fish because everyone knows the fish dont exist, and you must not eat the exotic food because doing so means you are oppressing someone, and you better not smell the flowers because those flowers are requiring renamed.

        Imagine Nepal is a holiday that is your own experience of your own illness.

        You have not asked for an intrusive tour guide.

        That tour guide might be a psychiatrist. Or that tour guide might be a school teacher. Or that tour guide might be a parent. Or that tour guide might be a therapist. Or that tour guide might be a friend.

        It is okay to give advice. Advice is not bullying. Advice does not come from place of fear. Everyone needs advice.

        There is a difference between advice given to someone’s Nepal experience and bullying them to see only in one particular way.

        There is a difference between advice given about an experience of illness and bullying someone elses experience of illness.

        Nobody should be bullying someone who feels they do have an illness. And nobody should be bullying someone who feels they do not.

        Most of the world are not casualties of events so much as they are casualties of intimate moments of cruel bullying. Bullying driven by unrecognized fear of relinquishing control of other peoples freedom of choice. Your freedom of choice. My freedom of choice.

        You have a right to your freedom of choice. And I have a right to my freedom of choice. We are like two kids with a play box. I have a right to choose this schizophrenia toy for myself, and you have a right to choose your holistic approach toy or whatever you like for you.

        To foster a world where that is not possible is to invite a world where if an individual chooses a trauma toy another individual can bully them to put that down.

        Respecting the individual is like respecting a moon rock as being utterly unique. It is not about adhering to an abstract idea of what respect should perform like. For any performance at respect, like in the Power Threat Meaning schools of paradigms, is merely doing a charade of respecting an individual. It is like going to a restaurant and getting served not what you uniquely like but getting served the best of the latest paradigm of respectableness. As if you are a widget in a paradigm. A cog. This has nothing to do with listening to you the individual.

        I have said before that ideally psychiatry or any form caring service should not be a big behemoth but broken into islands that cater more for individual preferences. This would guard against bullying. A person with a selection of tour guides need not stick with the one who keeps telling them how to view everything.

  5. I don’t know too much about metabolic syndrome or dysfunction in metabolic pathways , but I hope our family experience might be of interest to readers/researchers. In recent years my husband had been showing very gradual progression into dementia. Eighteen months ago he, in error, took my adult son’s morning meds [Two antipsychotics – laid out in another room.] He ended up in hospital for a month and in the interim lost 40 years of memory. Wham, bang – overnight. I had hoped that as toxins cleared from his body/brain that the memory loss would improve, but that has not happened. Some part of his brain has been catastrophically, permanently damaged – with one dose of psychiatric drugs. The hippocampus? It’s terrifying the damage these drugs can cause – but I think it’s fairly clear that damage can include dementia!

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