Discontinuing Amantadine in a Patient on 100mg
Amantadine should never be discontinued abruptly—taper gradually over several weeks to months to prevent potentially life-threatening withdrawal complications including parkinsonian crisis, delirium, and neuroleptic malignant syndrome. 1
Critical Warning About Abrupt Discontinuation
The FDA drug label explicitly warns against sudden discontinuation of amantadine, as this can precipitate severe complications 1:
- Parkinsonian crisis (sudden marked clinical deterioration) has occurred when amantadine was stopped abruptly in Parkinson's disease patients 1
- Withdrawal syndrome can include delirium, agitation, delusions, hallucinations, paranoid reaction, stupor, anxiety, depression, and slurred speech 1
- Neuroleptic malignant syndrome (NMS) has been reported with dose reduction or withdrawal, characterized by fever, muscle rigidity, altered consciousness, autonomic dysfunction, and elevated creatine phosphokinase 1
Recommended Tapering Strategy
Reduce the dose gradually over a minimum of several weeks, with slower tapers (weeks to months) preferred for patients on chronic therapy:
- Start by reducing to 50mg daily (half the current dose) and maintain this for at least 1-2 weeks while monitoring closely 1, 2
- Further reduce to 50mg every other day for another 1-2 weeks before complete discontinuation 2, 3
- For patients with Parkinson's disease or those on long-term therapy, consider an even slower taper over 2-3 months to minimize withdrawal risk 1, 2
The evidence from case reports demonstrates that withdrawal symptoms can emerge within 2-4 days of discontinuation and may persist for over a week 2, 3.
Monitoring During Discontinuation
Observe patients carefully throughout the taper for early signs of withdrawal syndrome:
- Mental status changes: confusion, delirium, agitation, hallucinations, or altered consciousness 1, 2
- Motor symptoms: increased rigidity, involuntary movements, worsening parkinsonian features 1, 3
- Autonomic instability: fever, tachycardia, blood pressure fluctuations 1, 3
- Behavioral changes: anxiety, depression, paranoia 1, 2
Case reports show that symptoms may be masked in medically complex patients or those with concurrent delirium from other causes 2.
Management of Withdrawal Symptoms
If withdrawal symptoms develop, immediately restart amantadine at the previous effective dose:
- Symptoms typically resolve within 24-48 hours of reintroducing amantadine 2, 3
- Once stabilized, resume tapering at a much slower rate (reducing by 25mg every 2-4 weeks) 2
- Severe cases presenting with NMS features require intensive supportive care, medical monitoring, and consideration of dopamine agonists like bromocriptine 1
Special Considerations
Patients at highest risk for withdrawal complications:
- Those with Parkinson's disease (highest risk of parkinsonian crisis) 1, 2
- Patients on concurrent neuroleptics (increased NMS risk) 1
- Elderly patients or those with renal impairment (altered pharmacokinetics) 1, 4
- Patients on high doses or long-term therapy 2, 3
Common pitfall to avoid: Holding amantadine during acute illness or hospitalization without planning for gradual discontinuation—this has led to severe withdrawal syndromes in case reports 2, 3. If oral intake is compromised, consider alternative routes or temporary dose adjustments rather than abrupt cessation.
The pharmacokinetics of amantadine show wide distribution and primarily renal elimination, meaning the drug clears slowly and withdrawal effects relate to dopamine depletion in cortical and limbic regions 4, 2.