Can Excessive Benztropine (Cogentin) Cause Psychosis?
Yes, excessive doses of benztropine can precipitate toxic psychosis, particularly in elderly patients with Parkinson's disease or those receiving neuroleptic drugs, and this risk increases with large doses or in susceptible patients. 1
Mechanism and Risk Factors
The FDA drug label explicitly warns that benztropine can cause "intensification of mental symptoms" and "toxic psychosis" in patients with mental disorders being treated with neuroleptic drugs (e.g., phenothiazines). 1 The label further states that "in such cases, antiparkinsonian drugs can precipitate a toxic psychosis." 1
Specific High-Risk Scenarios:
- Mental confusion and excitement occur with large doses 1
- Visual hallucinations have been reported occasionally 1
- Susceptible patients are at particular risk even at standard doses 1
- Patients with pre-existing mental disorders require careful observation, especially at the beginning of treatment or if dosage is increased 1
Overdose Presentation
In overdose situations, benztropine produces classic anticholinergic toxicity that includes prominent psychiatric symptoms: 1
- Intensification of mental symptoms or toxic psychosis in patients with mental illness being treated with neuroleptic drugs 1
- Hallucinations (especially visual) 1
- Confusion, nervousness, delirium 1
- CNS depression preceded or followed by stimulation 1
Clinical Context in Parkinson's Disease
This is particularly relevant because benztropine is commonly used to treat drug-induced parkinsonism. The 2016 Pediatrics guideline notes that drug-induced Parkinsonism syndrome is often treated by adding an anticholinergic agent (like benztropine), but emphasizes that early diagnosis and rapid withdrawal of the offending drug may improve the possibility of complete recovery. 2
The Dilemma:
Research evidence confirms that in Parkinson's disease patients, psychotic symptoms develop in 20-30% of patients receiving chronic anti-PD medications, and anticholinergics like benztropine are among the first medications that should be eliminated when psychosis occurs. 3 The recommended withdrawal order is: first anticholinergics, amantadine and selegiline; second dopamine agonists; and finally levodopa/carbidopa. 3
Practical Management Algorithm
When psychosis occurs in a patient on benztropine:
Immediately assess for anticholinergic toxicity - look for mydriasis, dry mouth, tachycardia, hyperthermia, urinary retention 1
Consider dose reduction or discontinuation - benztropine has cumulative action requiring continued supervision 1
Rule out other triggers - infections, metabolic disorders, subdural hematoma, other hallucinogenic drugs 3
Do NOT add typical antipsychotics - they will worsen parkinsonism and compound the problem 4, 5
If antipsychotic needed after benztropine withdrawal, use quetiapine (starting 25mg), clozapine, or pimavanserin - these are the only antipsychotics that don't significantly worsen parkinsonism 2, 5
Critical Pitfall to Avoid
Never combine benztropine with typical antipsychotics like haloperidol in elderly patients. The 2019 AGS Beers Criteria strongly recommends avoiding antipsychotics in older adults with Parkinson's disease except for quetiapine, clozapine, and pimavanserin. 2 Adding benztropine to treat the extrapyramidal symptoms from haloperidol creates a dangerous situation where the anticholinergic can precipitate psychosis while the antipsychotic blocks the very dopamine receptors needed for motor function. 6
Bottom Line for Elderly Patients
In elderly patients with Parkinson's disease or drug-induced parkinsonism, benztropine should be used at the lowest effective dose for the shortest duration, and should be the first medication withdrawn if psychosis develops. 1, 3 The cumulative anticholinergic effects combined with age-related cholinergic deficits make this population particularly vulnerable to toxic psychosis. 4