Trihexyphenidyl Should Be Avoided in Tardive Dyskinesia
Trihexyphenidyl (and other anticholinergic agents) should not be used to treat tardive dyskinesia and may actually worsen the condition. 1, 2, 3
Why Anticholinergics Are Contraindicated
The FDA drug label for trihexyphenidyl explicitly states: "Antiparkinsonism agents do not alleviate the symptoms of tardive dyskinesia, and in some instances may aggravate them" and "Trihexyphenidyl HCl is not recommended for use in patients with tardive dyskinesia unless they have concomitant Parkinson's disease." 3
Clinical guidelines from the American Academy of Family Physicians specifically recommend avoiding benztropine or trihexyphenidyl when extrapyramidal symptoms occur in elderly patients on typical antipsychotics. 1, 2 This recommendation extends to tardive dyskinesia management, where anticholinergics can worsen the involuntary movements. 3, 4
Evidence of Harm
Anticholinergics may induce or worsen dyskinesia: Case reports document severe choreoathetoid movements and orolingual dyskinesia directly caused by trihexyphenidyl, which resolved upon drug withdrawal. 5
Increased risk during concomitant use: The FDA label warns that "there may be an increased risk for the development of tardive dyskinesia during concomitant administration of anticholinergics and neuroleptics." 3
Comprehensive reviews confirm lack of benefit: A systematic review of 285 treatment studies involving over 3,000 patients concluded that "anticholinergic drugs are generally not recommended for treating dyskinetic patients." 4
Recommended Management Approach Instead
First-line strategy: Withdraw the offending antipsychotic if clinically feasible. 2, 6 This reverses dyskinesia in approximately 37% of patients. 4
Second-line strategy: Switch to atypical antipsychotics with lower D2 receptor affinity (such as clozapine or quetiapine) if continued antipsychotic treatment is necessary. 2, 6
Third-line strategy: Use FDA-approved VMAT2 inhibitors (valbenazine or deutetrabenazine) for persistent tardive dyskinesia requiring specific treatment. 2, 6
Critical Exception
The only scenario where trihexyphenidyl might be considered is when a patient has both tardive dyskinesia AND concomitant Parkinson's disease, as the anticholinergic may relieve some parkinsonian symptoms. 3 However, even in this situation, extreme caution is warranted as the tardive dyskinesia symptoms may worsen. 3
Common Pitfall to Avoid
Do not confuse drug-induced parkinsonism (an acute extrapyramidal side effect that may respond to anticholinergics) with tardive dyskinesia (a chronic movement disorder that worsens with anticholinergics). 1 These conditions often coexist in patients on chronic neuroleptic treatment, making clinical assessment challenging. 3