Polypharmacy in Schizophrenia May Have Adverse Effect on Cognition

A common strategy in the USA is to give patients multiple different types of antipsychotic medications. It doesn’t have much scientific support, and this new study further calls it into question:

Researchers identified an adverse effect threshold of anticholinergic burden on cognition in clinically stable patients with schizophrenia, according to a study published in Schizophrenia Research.

Since medications with high anticholinergic activity may adversely affect cognition and quality of life, Seenae Eum, PharmD, and colleagues from the department of experimental and clinical pharmacology at the College of Pharmacy, University of Minnesota, Minneapolis, researched the cognitive effects of multiple drug treatments on patients with psychotic disorders.

“To our knowledge, this is the first study to identify a potential threshold effect of cumulative anticholinergic burden on neuropsychological performance using medication regimen data from clinically stable patients with schizophrenia,” Ms Eum said.

FUll story:



Yes we learned in my neuropsychopharmacology class that polypharmacy with multiple antipsychotics is dangerous and not recommended unless someone is treatment resistant.

These are serious meds with strong side effects and at times very harmful long term effects…combining two is just not advisable unless absolutely necessary…

(People often say “but I’m on seroquel and x!!” That’s not the same, seroquel doesn’t function as an AP at lower doses, it functions as an AD or even a sleep aid, a lot of docs use this as adjunct to avoid addictive anti anxiety meds like benzos)


It’s really a question of whether the drugs have a high cholinergic burden or not.

Some APs have higher and some lower anti cholinergic burdens.

Some ADs have high anti cholinergic burdens too, like Elavil. And others do not function that way.

So it’s not really how many APs you are on, but how they act, and whether your other meds are anti cholinergic.

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Seroquel has moderate anti cholinergic activity.

But Zyprexa, Cogentin, Vistaril, and Clozapine have high anti cholinergic activity.

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I’m on Cogentin and Vistaril. Maybe that is why I have short term memory problems.

Lately I’ve been missing words as I read. I lose or skip over a word at the beginning of a sentence and it confuses me. I have to look up and plug the word in to make it make sense. That is why I haven’t been reading as much. I still read mostly, but I get tired sooner.

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My psychiatrist was against the idea of me going on 2 different Antipsychotics at the same time when the subject was brought up.
Poly pharmacy should be reserved for treatment resistant patients only.

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Polypharmacy has saved my life. But I am treatment resistant (clozapine resistant too).

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@twinklestars I have no idea where you get this from, seems like rubbish to me.
For example, clozapine has 5 times more potent anticholinergic properties than Olanzapine

I get it from various web searches. Here is a chart showing anti cholinergic medication, the meds in group 3 are considered to have high burdens.


Your article is interesting, both in that the participants in the study had no cognitive deficits, and also the difference in blood levels. I do not know whether this is because they only classify drugs as low, moderate and high anti cholinergic, and there is no “ultra high” category, or if there is another reason. However, Zyprexa /Olanzapine is in the high anti cholinergic activity category in several separate sites I’ve reviewed.

This particular chart classes Seroquel in the high category while others say moderate, so there does not appear to be a single standard.


@twinklestars please post or send me in a PM all the charts.
It is important as anticholinergic drugs may impair cognition.
I am olanzapine and inclined to quickly quit and move to lurasidone as anticholinergic effects
especially over the long term may cause cognitive impairment, and good cognition is something
I value above all else.
So please post the charts that rate medications according to anticholinergic burden.
Are there any cholinergic antipsychotics btw?
What about lurasidone?

I’ve been taking 4 mg daily of cogentin. It does impair my cognition but I think it kind of helps me in other areas.

There is a link in my earlier post to one source, and here is another, but as you can see, they don’t agree on just how anti cholinergic each of the medications are.

Click on the chart to see a table of medications ranked 1 to 3.

The study you posted did not show any cognitive deficits in those patients, so I think that is a good sign. You should take the medication that works for you, though it may have some anti cholinergic effect, it may not be enough to be a burden. Ask your doctor to consider the total anti cholinergic burden, you can avoid other anti cholinergic medication like allergy and muscle relaxants. Don’t decide on your medication only on the basis of one neurotransmitter, but the entire effect on your state of mind.
*ETA especially since there doesn’t seem to be consensus on which drugs are most anti cholinergic.

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