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)
“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.
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.