Can benztropine (anticholinergic) and amantadine (dopamine agonist) be taken together for Extrapyramidal Symptoms (EPS) prophylaxis?

Benztropine and Amantadine Can Be Used Together for EPS Prophylaxis

Yes, benztropine and amantadine can be used together for extrapyramidal symptoms (EPS) prophylaxis, as they work through different mechanisms and may provide complementary benefits when managing drug-induced EPS. 1

Mechanisms and Rationale

• Benztropine: Acts as an anticholinergic agent that blocks cholinergic activity in the basal ganglia 2
• Amantadine: Functions as a dopamine agonist, increasing dopamine availability 3
• Complementary action: The different mechanisms provide a physiological basis for their combined use in managing EPS

Evidence Supporting Combined Use

The American Academy of Child and Adolescent Psychiatry guidelines specifically mention medication combinations to address side effects of an effective agent, including "benztropine for extrapyramidal symptoms secondary to an antipsychotic" 1. While amantadine is not specifically mentioned in this context, its FDA-approved indication includes "treatment of drug-induced extrapyramidal reactions" 3.

Research has shown that:

• Amantadine is comparable in effectiveness to benztropine for treating EPS 4, 5
• Amantadine produces fewer anticholinergic side effects than traditional antiparkinsonian medications 4
• Amantadine may be particularly useful in patients who cannot tolerate medications with anticholinergic properties 4

Clinical Approach to EPS Management

For Prophylaxis:

1. Assess risk factors for developing EPS:

   • Elderly or very young patients
   • Male gender
   • Previous history of tremors
   • Previous use of antipsychotics
   • Polypharmacy
   • Substance abuse
   • Higher doses of antipsychotics 6

2. Consider prophylaxis only in high-risk patients:

   • Routine prophylaxis is not recommended for all patients 7
   • If initiated, prophylactic treatment should be discontinued after approximately two weeks 7

3. Dosing considerations:

   • Benztropine: Start with 0.5-1 mg daily, can increase to 1-2 mg daily (maximum 6 mg daily) 2
   • Amantadine: Start with lower doses and increase gradually to minimize side effects 3

For Treatment of Established EPS:

• Acute dystonia: Anticholinergic medications (benztropine) or antihistamines 6
• Drug-induced parkinsonism: Consider reducing antipsychotic dose, adding benztropine (1-2 mg/day), or amantadine 6
• Akathisia: Reduce antipsychotic dose if possible, consider beta-blockers or benzodiazepines (anticholinergics less effective) 6

Important Considerations and Precautions

1. Monitor for combined side effects:

   • CNS effects (confusion, sedation)
   • Anticholinergic effects (dry mouth, constipation, urinary retention)
   • Potential for additive adverse effects

2. Dosage adjustments:

   • Start with lower doses of each medication when using in combination
   • Titrate gradually based on response and tolerability
   • Elderly patients require lower doses due to increased sensitivity to CNS effects 6

3. Duration of treatment:

   • Long-term use of antiparkinsonian medications is generally not recommended 7
   • Consider gradual withdrawal after stabilization of symptoms

4. Contraindications:

   • Amantadine has anticholinergic effects and should not be used in patients with untreated angle closure glaucoma 1
   • Use with caution in patients with renal insufficiency, seizure disorders, or psychiatric disorders 1

By using both medications with careful monitoring and appropriate dosing, you can effectively manage or prevent EPS while minimizing the side effects associated with either agent alone.