What is the preferred choice between Artane (trihexyphenidyl) and amantadine for geriatric patients with Parkinson's disease or drug-induced parkinsonism, considering potential side effects and interactions?

Avoid Artane (Trihexyphenidyl) in Geriatrics; Use Amantadine with Caution at Reduced Doses

In geriatric patients, amantadine is the preferred choice over Artane (trihexyphenidyl), but must be used at reduced doses not exceeding 100 mg/day due to age-related decline in renal function and increased risk of serious CNS toxicity. 1, 2, 3

Why Artane Should Be Avoided in Elderly Patients

Guidelines explicitly recommend avoiding trihexyphenidyl (Artane) in geriatric patients with drug-induced extrapyramidal symptoms. 1 The American Family Physician guidelines state that when extrapyramidal symptoms occur from typical antipsychotics, clinicians should "decrease dosage or switch to another agent; avoid use of benztropine (Cogentin) or trihexyphenidyl (Artane)." 1

Specific Risks of Artane in the Elderly

• Cognitive dysfunction is a major concern, as trihexyphenidyl causes confusion and memory impairment in elderly patients, particularly those over age 60. 4
• Increased sensitivity to anticholinergic effects occurs with aging, requiring elderly patients to be started on low doses and observed closely. 4
• Anticholinergic burden includes risks of urinary retention, untreated angle-closure glaucoma complications (mydriasis), heat intolerance, and paralytic ileus. 4

Amantadine: The Preferred Alternative with Critical Dosing Restrictions

Mandatory Dose Reduction in All Geriatric Patients

The maximum daily dose of amantadine in patients ≥65 years must not exceed 100 mg for either prophylaxis or treatment (not the standard 200 mg/day used in younger adults). 1, 2, 3 This restriction exists because:

• Renal function declines with increasing age, and amantadine is excreted unchanged in the urine with substantially reduced clearance in elderly patients. 1, 3
• Dose-dependent toxicity occurs at standard adult doses in geriatric populations. 2, 3

Further Dose Reduction May Be Required

Some elderly patients require doses below 100 mg/day to minimize serious CNS toxicity. 2, 3 Specific high-risk groups include:

• Elderly women are at higher risk than elderly men for side effects at 100 mg/day due to smaller average body size. 3
• Any degree of renal impairment (creatinine clearance ≤50 mL/min/1.73m²) requires dose reduction to prevent drug accumulation. 1, 2, 3
• Patients with seizure disorders or psychiatric history need close observation and potential dose reduction below 100 mg/day. 3

Clinical Algorithm for Amantadine Use in Geriatrics

1. Verify renal function before initiating amantadine in any elderly patient. 2, 3

2. Start at 100 mg/day maximum (not 200 mg/day), and consider starting below 100 mg/day for elderly women, those with any renal impairment, or those with seizure/psychiatric history. 2, 3

3. Monitor closely for CNS toxicity (confusion, hallucinations, agitation, delirium, marked behavioral changes) especially during the first week of treatment. 2, 3

4. Reduce dose or discontinue immediately if serious side effects emerge. 3

Side Effect Profile Favoring Amantadine

Amantadine produces fewer and less severe side effects compared to anticholinergic agents like Artane. 5 Research demonstrates that:

• Anticholinergics severely impair memory acquisition in elderly subjects more than in young adults, affecting free recall, recognition memory, and mood. 6
• Amantadine does not impair new memory acquisition and is significantly better tolerated on self-report measures. 6
• CNS side effects occur in approximately 13% of patients at standard dosing (nervousness, anxiety, insomnia, difficulty concentrating, lightheadedness), but these are mild and cease soon after discontinuation. 3

Common Pitfalls to Avoid

• Do not use the standard 200 mg/day dose in elderly patients—this is the most critical error leading to serious toxicity. 1, 2, 3
• Do not assume 100 mg/day is safe for all elderly patients—women and those with renal impairment may need further reduction. 2, 3
• Do not fail to check renal function before initiating therapy, as this determines appropriate dosing. 2, 3
• Do not combine amantadine with alcohol or CNS depressants, as additive sedative effects occur. 4
• Monitor for serious CNS toxicity (plasma concentrations >3000 ng/mL associated with myoclonus, hallucinations, delirium) even in patients without prior psychiatric symptoms. 2

FDA-Approved Indications Support This Use

Amantadine is FDA-approved for treatment of drug-induced extrapyramidal reactions and has a lower incidence of anticholinergic-type side effects compared to anticholinergic antiparkinson drugs. 7 The FDA label notes that amantadine is indicated in the treatment of drug-induced extrapyramidal reactions with fewer anticholinergic side effects than traditional agents. 7