How is drug-induced parkinsonism typically managed?

Management of Drug-Induced Parkinsonism

The first-line management for drug-induced parkinsonism is discontinuation of the offending medication whenever possible, as this leads to significant improvement in most cases, though complete resolution may take up to 6-18 months. 1, 2

Clinical Features and Diagnosis

• Drug-induced parkinsonism (DIP) is one of the most common iatrogenic movement disorders, characterized by tremors, bradykinesia, rigidity, and postural instability that can be clinically indistinguishable from idiopathic Parkinson's disease 1
• DIP typically presents with acute to subacute onset of symptoms after exposure to dopamine receptor blocking agents (DRBAs) 1
• Unlike idiopathic Parkinson's disease, DIP is more likely to present with bilateral and symmetrical symptoms and may be less likely to produce tremor 3
• DIP often co-occurs with other drug-induced movement disorders such as tardive dyskinesia 4

Causative Agents

• The most common causative medications include:
  • Antipsychotics (both typical and atypical, except clozapine) 3, 4
  • Antiemetics with dopamine-blocking properties (e.g., metoclopramide) 5
  • Calcium channel blockers (e.g., flunarizine, cinnarizine) 2, 5
  • Other medications including reserpine, tetrabenazine, and alpha-methyldopa 5

Risk Factors

• Advanced age (elderly patients are at significantly higher risk) 2, 3
• Female sex 3
• Pre-existing cognitive impairment 3
• Higher potency, dose, and longer duration of treatment with the offending agent 3
• Pre-existing extrapyramidal signs 3
• Polypharmacy, common in elderly patients 2

Management Algorithm

Step 1: Identify and Discontinue the Offending Agent

• Whenever clinically possible, discontinue the causative medication 1, 2, 3
• If the medication cannot be discontinued completely:
  • Consider dose reduction 1
  • Switch to an agent with lower risk for DIP (e.g., quetiapine or clozapine for antipsychotics) 1, 3

Step 2: Symptomatic Treatment (If Discontinuation Is Not Possible or Symptoms Persist)

• For mild to moderate symptoms:

  • Anticholinergic medications such as trihexyphenidyl may be used, particularly effective for tremor and rigidity 6, 7
  • Initial dose of trihexyphenidyl should be low (1 mg daily) and then increased gradually by 2 mg increments every 3-5 days, with total daily dosage usually ranging between 5-15 mg 7
  • Caution: Anticholinergic agents should be used carefully in elderly patients due to potential cognitive side effects 6, 3

• Alternative pharmacological options:

  • Amantadine may be preferred, especially in patients with comorbid tardive dyskinesia, as anticholinergics can worsen TD 4
  • Dopaminergic agents (levodopa or dopamine agonists) may be considered in selected cases where there is evidence of dopamine nerve terminal defects 3

Step 3: Monitoring and Follow-up

• Monitor for symptom improvement after discontinuation of the offending agent 2
• Be aware that symptoms may persist or remit slowly in up to 10% of patients 3
• If symptoms persist beyond 6-18 months after discontinuation, consider reevaluation for possible underlying idiopathic Parkinson's disease 2, 3

Special Considerations

• In cases where the diagnosis is unclear between DIP and idiopathic Parkinson's disease, functional neuroimaging tests evaluating striatal dopamine transporters (DATs) may be helpful 3
• Prophylactic treatment with anticholinergics is not indicated when starting patients on antipsychotics 1
• When managing DIP in patients who also have tardive dyskinesia, be aware that anticholinergics can worsen TD symptoms 4

Prevention Strategies

• Use the lowest effective dose of antipsychotics or other DRBAs 2, 3
• Consider atypical antipsychotics with lower risk of extrapyramidal symptoms when possible 3
• Regular monitoring for early signs of parkinsonism in patients on DRBAs 2
• Increased awareness among healthcare providers about medications that can cause DIP 2
• Avoid polypharmacy, particularly in elderly patients 2

Remember that early recognition and prompt discontinuation of the offending agent are the keys to successful management of drug-induced parkinsonism 2, 3.