What is Trihexyphenidyl?

Trihexyphenidyl: A Synthetic Anticholinergic Medication for Parkinsonism and Extrapyramidal Symptoms

Trihexyphenidyl is a synthetic anticholinergic medication primarily indicated for treating parkinsonism and extrapyramidal symptoms caused by antipsychotic medications, but it carries significant abuse potential and should be used cautiously with regular monitoring for side effects. 1

Mechanism of Action and Pharmacology

Trihexyphenidyl works by:

• Directly inhibiting the parasympathetic nervous system
• Exerting a relaxing effect on smooth musculature through both:
  • Direct action on muscle tissue
  • Indirect inhibition of the parasympathetic nervous system 1

Its pharmacokinetic properties include:

• Rapid absorption with a biphasic distribution pattern in new users
• First-order elimination kinetics
• Relatively short half-life of approximately 3.7 hours 2

Clinical Indications

Trihexyphenidyl is FDA-approved for:

1. Primary indication: Treatment of all forms of parkinsonism (postencephalitic, arteriosclerotic, and idiopathic)
2. Secondary indication: Control of extrapyramidal disorders caused by central nervous system drugs, including:
   • Dibenzoxazepines
   • Phenothiazines
   • Thioxanthenes
   • Butyrophenones 1

Dosing Considerations

For management of extrapyramidal symptoms:

• Starting dose: 1-2 mg daily
• Maximum dose: 6 mg daily 3
• Dosing should be carefully monitored and limited to the minimum effective dose
• Duration should be limited to short-term management of significant extrapyramidal symptoms, particularly after dose reduction and switching strategies for antipsychotics have proven ineffective 3

Adverse Effects and Monitoring

Common adverse effects include:

• Anticholinergic effects: dry mouth, blurred vision, urinary retention, constipation
• Central nervous system effects: confusion, memory impairment, hallucinations
• Cardiovascular effects: tachycardia, orthostatic hypotension 3, 4

Special monitoring considerations:

• Elderly patients are at higher risk for anticholinergic side effects
• Young males are at higher risk for acute dystonic reactions
• Regular monitoring for signs of abuse or misuse is essential 3

Abuse Potential and Risks

Trihexyphenidyl has significant abuse potential:

• Reported to produce euphoric effects, mood elevation, and social stimulation 5, 6
• Cases of abuse with doses up to 200 mg/day have been documented 5
• Abuse is particularly concerning in patients with schizophrenia 7
• Abrupt discontinuation can lead to a withdrawal syndrome characterized by:
  • Increased anxiety
  • Physical complaints
  • Orthostatic hypotension
  • Tachycardia
  • Temporary worsening of psychotic and extrapyramidal symptoms 4

Alternative Medications and Treatment Strategies

When extrapyramidal symptoms require treatment, consider:

1. First approach: Reduce antipsychotic dose or switch to an atypical antipsychotic with lower EPS risk (e.g., olanzapine, quetiapine) 3
2. Alternative medications with potentially fewer anticholinergic effects:
   • Amantadine (has fewer anticholinergic effects)
   • Beta-blockers (particularly for akathisia)
   • Benzodiazepines (for short-term management of akathisia) 3

Clinical Pearls and Pitfalls

• Diagnostic pitfall: Akathisia is often misdiagnosed as psychotic agitation or anxiety, leading to inappropriate treatment 3
• Prescribing pitfall: Patients may feign extrapyramidal symptoms to obtain trihexyphenidyl for its euphoric effects 5
• Treatment pitfall: High doses may precipitate anticholinergic toxic psychosis and interfere with antipsychotic efficacy 5
• Monitoring pitfall: Failure to recognize the withdrawal syndrome when discontinuing trihexyphenidyl 4

For optimal patient outcomes, trihexyphenidyl should be prescribed at the lowest effective dose for the shortest duration necessary, with careful monitoring for both therapeutic effects and signs of misuse.