How to manage drug-induced Parkinson's disease?

Management of Drug-Induced Parkinsonism

The first-line approach to managing drug-induced parkinsonism is discontinuation of the offending medication whenever clinically possible. 1

Understanding Drug-Induced Parkinsonism

Drug-induced parkinsonism (DIP) is one of the most common iatrogenic movement disorders, accounting for approximately 4% of all parkinsonism cases seen in neurology clinics. It is characterized by:

• Tremors
• Bradykinesia (slowness of movement)
• Rigidity
• Shuffling gait with postural instability

These symptoms are clinically indistinguishable from idiopathic Parkinson's disease, making diagnosis challenging without a careful medication history.

Common Causative Medications

The most frequent offending agents include:

• Antipsychotics (particularly first-generation/typical antipsychotics)
• Antiemetics (metoclopramide, prochlorperazine)
• Calcium channel blockers (flunarizine, cinnarizine)
• Selective serotonin reuptake inhibitors (SSRIs)
• Antiarrhythmics
• Antiepileptics
• Cholinomimetics

Diagnostic Approach

1. Establish temporal relationship: Acute to subacute onset of parkinsonian symptoms while taking a dopamine receptor blocking agent (DRBA)
2. Differentiate from idiopathic Parkinson's disease:
   • Symmetrical symptoms (vs. asymmetrical in idiopathic PD)
   • Predominant rigidity and bradykinesia with less tremor
   • Absence of response to levodopa challenge
3. Consider ancillary testing:
   • DaT scan (Dopamine Transporter SPECT) - will show normal radiotracer uptake in DIP but decreased uptake in true Parkinson's disease 2, 3
   • MRI brain - typically normal in both conditions but helps rule out other causes

Treatment Algorithm

1. Discontinue the offending agent 1, 3, 4

   • If possible, completely withdraw the causative medication
   • If withdrawal is not possible (e.g., antipsychotics for psychiatric conditions):
     • Reduce the dose to the minimum effective level
     • Consider switching to an atypical antipsychotic with lower risk of DIP (quetiapine or clozapine)

2. Monitor for symptom resolution

   • Complete remission typically occurs within 6-18 months after drug withdrawal in most patients 5
   • At least 10% of patients may develop persistent and progressive parkinsonism despite discontinuation, suggesting unmasking of underlying presymptomatic Parkinson's disease 4

3. Symptomatic treatment (only if symptoms are disabling and discontinuation is not possible):

   • Anticholinergics: Consider for younger patients with prominent tremor
     • Examples: trihexyphenidyl, benztropine
     • Caution: May cause cognitive impairment, especially in elderly
   • Amantadine: FDA-approved for drug-induced extrapyramidal reactions 6
     • Lower incidence of anticholinergic side effects compared to anticholinergic agents
     • Starting dose: 100 mg daily, can increase to 100 mg twice daily
   • Levodopa: Consider only for patients with persistent symptoms after drug withdrawal who may have underlying idiopathic Parkinson's disease 7

Special Considerations

Elderly Patients

• Higher risk due to age-related decrease in dopaminergic neurons
• Often on multiple medications (polypharmacy)
• More sensitive to anticholinergic side effects
• Lower doses of symptomatic medications should be used

Psychiatric Patients

• When antipsychotics cannot be discontinued:
  • Switch to atypical antipsychotics with lower DIP risk
  • Quetiapine and clozapine have the lowest risk of causing DIP 3
  • Avoid prophylactic anticholinergics as they are not indicated and may worsen cognitive function 3

Prevention Strategies

Prevention is the best treatment approach for DIP 5, 4:

1. Avoid prescribing high-risk medications unless absolutely necessary
2. Use the lowest effective dose of potentially offending medications
3. Regular monitoring for early parkinsonian symptoms in high-risk patients
4. Exercise particular caution in:
   • Elderly patients
   • Patients with family history of parkinsonism or tremor
   • Patients requiring multiple medications for prolonged periods

Prognosis

• Most cases (approximately 90%) resolve within 6-18 months after drug withdrawal 5
• Persistent symptoms beyond 6 months after discontinuation may indicate:
  • Underlying presymptomatic Parkinson's disease unmasked by the medication
  • Permanent damage to dopaminergic neurons from prolonged drug exposure

Common Pitfalls to Avoid

1. Misdiagnosing DIP as idiopathic Parkinson's disease, leading to unnecessary long-term dopaminergic therapy
2. Failing to recognize the causative medication
3. Adding anti-parkinsonian medications without attempting to withdraw the offending agent
4. Overlooking the possibility of underlying presymptomatic Parkinson's disease in cases of persistent symptoms
5. Using high-dose anticholinergics in elderly patients, which can cause significant cognitive impairment

By following this structured approach to diagnosis and management, clinicians can effectively address drug-induced parkinsonism while minimizing unnecessary treatments and complications.