All anticholinergics are potentially unhealthy, and many psychiatric drugs carry anticholinergic load without being called that, from olanzapine and quetiapine to paroxetine and diphenhydramine. Benztropine itself is fine when it is needed; the rule is not to give medication people do not need. Keep the total burden down, especially with clozapine.
Pearls
All anticholinergics are potentially unhealthy, and we give tons of them without calling them poison. Benztropine is perfectly fine; just do not give a medication people do not need.
“All anticholinergics are potentially unhealthy. We give tons of anticholinergics without calling them poison. Benztropine is perfectly fine. You just shouldn't give a medication that people don't need”
Choosing Antipsychotics in Schizophrenia: Side-Effects, Maximizing Efficacy, and Finding the Right Medication | Episode 17Feb 2025 Paroxetine is anti-muscarinic, and that organizes its problems: it is sedating, and it has bad withdrawal, as any anti-muscarinic medication will.
“paroxetine is anti-muscarinic, and that helps me to organize all the information that you kind of just mentioned. So it is sedating. It does have bad withdrawal because we know any anti-muscarinic medication is going to have bad withdrawal”
30:08Antidepressant Tier List: Psychiatrists Rank Depression Medications for MDDMay 2026 100 mg of clozapine is roughly equal to 2 mg of benztropine, which is useful to know if you ever need to stop clozapine suddenly.
“100 milligrams of clozapine is actually equal to 2 milligrams of benztropine. And this can be helpful to know because if you ever need to stop the clozapine suddenly”
37:37Top 10 Things to Know About ClozapineDec 2025 They are very anticholinergic, which is part of why they work, but we do not like that for patients, so they go in the C tier.
“They're very anticholinergic as well, which is also part of why they work, and I don't like that for patients, so they go into the C tier”
44:46Sleep Medications Treatment Tier List: Best Insomnia Medications RankedAug 2026
Pitfalls
Many TCAs, paroxetine, anti-parkinsonian medications and bladder relaxants for overactive bladder are anticholinergic, and diphenhydramine is a big one.
“a lot of the TCAs have a lot of anti-muscarinic activity. Paroxetine is very anticholinergic. The anti-Parkinsonian medications, the meds that treat overactive bladder and that are bladder relaxants. Benadryl is a big one”
38:02Top 10 Things to Know About ClozapineDec 2025 The same doctors who say never prescribe benztropine will give olanzapine and quetiapine without blinking, and those are already anticholinergic.
“The same doctors who say never prescribe the Benzterpene are also the same ones who will not blink and give Zyprexa and Seroquel, which are themselves already anticholinergic”
Choosing Antipsychotics in Schizophrenia: Side-Effects, Maximizing Efficacy, and Finding the Right Medication | Episode 17Feb 2025
It also comes up on
- DiphenhydramineIn our opinion it is just too anticholinergic for sleep. We do not like to use it unless we are looking for anticholinergic effect alongside an antipsychotic.
- ClomipramineIt brings strong anticholinergic effects, QTc prolongation, heavy sedation and weight gain. Not necessarily the greatest choice, but if it is viable, you can consider it.
- OCDClomipramine has strong anticholinergic effects, QTc prolongation, heavy sedation and weight gain. Not the greatest choice, but consider it if viable.
- ParoxetineWe tend not to use it. It is anticholinergic and makes people sleepy, it causes weight gain, and it is probably the worst SSRI for pregnancy. Even where it helps, as in anxiety, these hold it back.
- ParoxetineC tier for sleep: the anticholinergic side effects and weight gain push it down, and there is not much reason to use it instead of mirtazapine.
- SSRIsParoxetine makes people a little sleepy from its anticholinergic effect and causes some weight gain, so we tend not to use it.
- AntipsychoticsThe HAM receptors explain much of the burden: histamine for sedation and weight gain, muscarinic for sedation and anticholinergic problems, alpha-1 for orthostatic hypotension. Many second-generation drugs block them.
- GabapentinFor sleep, give a medication, usually trazodone or gabapentin. Hydroxyzine is fine too. Avoid anticholinergics like Benadryl if you can.
From these episodes
- Sleep Medications Treatment Tier List: Best Insomnia Medications RankedAug 2026 · 1 point
- Antidepressant Tier List: Psychiatrists Rank Depression Medications for MDDMay 2026 · 1 point
- Top 10 Things to Know About ClozapineDec 2025 · 2 points
- Choosing Antipsychotics in Schizophrenia: Side-Effects, Maximizing Efficacy, and Finding the Right Medication | Episode 17Feb 2025 · 2 points
Every point above is something said on the Psychofarm podcast, with the words as spoken and a link to the moment in the episode. It is education, not medical advice, and an episode reflects what we thought when we recorded it.