Can Benztropine Cause Anxiety?
Yes, benztropine can cause anxiety as a documented adverse effect, and clinical evidence suggests it may worsen anxiety and depression compared to alternative anticholinergic agents.
Direct Evidence of Anxiety as a Side Effect
The most compelling evidence comes from a controlled clinical trial comparing benztropine to ethopropazine in 60 schizophrenic patients with neuroleptic-induced parkinsonism. Benztropine-treated patients experienced significantly more anxiety and depression than those receiving ethopropazine 1. This study concluded that benztropine should not be the anticholinergic drug of choice due to its "more toxic central and peripheral atropinic effect."
Additional research supports anxiety as a recognized adverse effect:
- A 2018 ESMO guideline on delirium management lists risperidone (an antipsychotic) as potentially causing "insomnia, agitation, anxiety" 2, and while this refers to a different medication, it establishes the pattern of anticholinergic and related medications causing anxiety
- Aripiprazole guidelines note it "may cause headache, agitation, anxiety, insomnia" 2, demonstrating that medications affecting similar pathways can induce anxiety
Mechanism and Clinical Context
Benztropine's anticholinergic properties affect the central nervous system broadly. The FDA label warns that benztropine "may impair mental and/or physical abilities" 3, though it does not explicitly list anxiety in standard adverse effect listings 3. However, the absence from FDA labeling does not negate clinical trial evidence.
Clinical Implications and Recommendations
When prescribing benztropine for extrapyramidal symptoms:
- Monitor patients specifically for new-onset or worsening anxiety and depression, particularly in those with pre-existing mood disorders
- Consider alternative anticholinergic agents (such as ethopropazine where available) if anxiety emerges or worsens 1
- Guidelines recommend avoiding benztropine use in elderly patients with Alzheimer's disease when managing antipsychotic-related extrapyramidal symptoms 4
Important caveats:
- The anxiety effect appears dose-related and may vary significantly between individuals
- One case report paradoxically described benztropine having an "augmenting antidepressant effect" at very low doses (0.25 mg daily) in a depressed Parkinsonian patient 5, suggesting complex, dose-dependent central effects
- Benztropine is frequently used long-term despite recommendations for short-term use (≤7 days for prophylaxis) 6, 7, potentially increasing exposure to adverse psychiatric effects
The evidence supports that benztropine can indeed cause anxiety, particularly compared to alternative anticholinergic medications, and clinicians should maintain vigilance for this adverse effect during treatment.