Does Benztropine Worsen Tardive Dyskinesia?
Yes, benztropine can worsen tardive dyskinesia and should not be used to treat this condition. 1, 2
Direct Evidence Against Benztropine Use in TD
The FDA drug label for benztropine explicitly states that "antiparkinsonism agents do not alleviate the symptoms of tardive dyskinesia, and in some instances may aggravate them" and that "benztropine mesylate is not recommended for use in patients with tardive dyskinesia." 2 The indication section further clarifies that benztropine is "useful also in the control of extrapyramidal disorders (except tardive dyskinesia)" due to neuroleptic drugs. 2
Guideline Recommendations
The American Academy of Family Physicians explicitly recommends avoiding benztropine or trihexyphenidyl when extrapyramidal symptoms occur in elderly patients on typical antipsychotics, which extends to tardive dyskinesia management where anticholinergics can worsen the involuntary movements. 1 Clinical guidelines emphasize that anticholinergics should not be used to treat tardive dyskinesia and may actually worsen the condition. 1
The Critical Distinction: Drug-Induced Parkinsonism vs. Tardive Dyskinesia
This is a crucial clinical pitfall to avoid: Anticholinergics like benztropine are beneficial for drug-induced parkinsonism but worsen tardive dyskinesia. 1, 3 The American Academy of Family Physicians emphasizes the importance of distinguishing between these two conditions before prescribing anticholinergics. 1
Key Distinguishing Features:
- Drug-induced parkinsonism presents with bradykinesia, rigidity, and rhythmic tremor, typically appearing within hours to weeks of antipsychotic initiation or dose increase. 4
- Tardive dyskinesia has delayed onset (typically after at least 3 months of treatment) and presents with involuntary abnormal facial movements such as lip smacking, puckering, chewing, or tongue protrusion. 4
Clinical Evidence of Worsening
A 1979 controlled study found that benztropine-treated patients had a significant increase in tardive dyskinesia compared to their condition during procyclidine treatment, suggesting that benztropine is not the anticholinergic drug of choice due to its more toxic central and peripheral atropinic effects. 5
What to Do Instead
If a patient has both drug-induced parkinsonism and tardive dyskinesia (which can coexist 6), amantadine (a non-anticholinergic agent) may be preferred as it can treat parkinsonism without worsening TD. 4
For tardive dyskinesia specifically:
- First-line: Use FDA-approved VMAT2 inhibitors (valbenazine or deutetrabenazine). 1
- Alternative approaches: Gradually withdraw the offending antipsychotic if clinically feasible, or switch to atypical antipsychotics with lower D2 affinity. 1, 3
Common Clinical Scenario to Avoid
The American Academy of Child and Adolescent Psychiatry warns that in patients with mental disorders on neuroleptics, antiparkinsonian drugs can precipitate toxic psychosis and may intensify mental symptoms, particularly at the beginning of treatment or with dosage increases. 7 This underscores the importance of careful patient selection and avoiding benztropine in TD patients.