How is drug-induced parkinsonism managed?

Management of Drug-Induced Parkinsonism

The first-line approach to drug-induced parkinsonism is discontinuation of the causative agent whenever possible, followed by anticholinergic medications such as trihexyphenidyl when discontinuation is not feasible. 1, 2

Diagnosis and Clinical Presentation

• 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 2
• Symptoms typically develop within hours to weeks after starting a dopamine receptor blocking agent (DRBA) or increasing its dosage 3
• DIP is more likely to present with symmetrical symptoms and less tremor compared to idiopathic Parkinson's disease 4
• When diagnostic uncertainty exists, dopaminergic imaging (DaTscan) may assist in differentiating drug-induced from neurodegenerative parkinsonism 5, 2

Management Algorithm

First-Line Approach

• Discontinue the offending medication whenever clinically possible 1, 2, 4
• For drug-induced REM sleep behavior disorder specifically, drug discontinuation is recommended over drug continuation 5
• When complete discontinuation is not possible, consider:
  • Reducing the dose of the causative agent 2
  • Switching to an agent with lower risk of parkinsonism (e.g., quetiapine or clozapine for antipsychotics) 6, 2

Pharmacological Management When Discontinuation Is Not Possible

1. Anticholinergic Medications:

   • Trihexyphenidyl is indicated for drug-induced parkinsonism with a total daily dosage usually ranging between 5-15 mg 1, 7
   • Initial dose should be low (1 mg daily) and then increased gradually by 2 mg increments at intervals of 3-5 days 7
   • Most effective for tremor and rigidity components of DIP 1
   • Use with caution in elderly patients due to potential cognitive side effects 1

2. Amantadine:

   • Alternative first-line agent particularly effective for rigidity and bradykinesia 1, 8
   • Preferred in patients with comorbid DIP and tardive dyskinesia, as anticholinergics can worsen tardive dyskinesia 3
   • Has lower incidence of anticholinergic-type side effects compared to anticholinergic antiparkinson drugs 8

3. Dopamine Agonists:

   • May be considered in refractory cases 1
   • Pramipexole can be started at 0.125 mg orally 2-3 hours before bedtime, with dose doubled every 4-7 days to a maximum of 0.5 mg 1

Special Considerations

• Abrupt withdrawal of treatment for parkinsonism should be avoided as it may result in acute exacerbation of symptoms or neuroleptic malignant syndrome 7
• Regular monitoring using standardized scales like the Abnormal Involuntary Movement Scale (AIMS) is recommended every 3-6 months 6, 1
• In patients with psychiatric conditions requiring antipsychotics, carefully balance the risk of psychotic relapse against the severity of parkinsonian symptoms 6
• Most cases of DIP resolve within 6-18 months after discontinuation of the offending agent, but approximately 10% of patients may develop persistent or progressive parkinsonism 9, 4, 10
• Elderly patients are at higher risk for DIP due to age-related factors and polypharmacy 9, 4

Prevention

• Use a "start low, go slow" approach to medication dosing, particularly in vulnerable populations 5
• Perform baseline and periodic assessments using standardized scales to detect early parkinsonian symptoms 6, 1
• When possible, avoid prescribing medications with high risk for DIP, especially in elderly patients or those with family history of parkinsonism 10
• Monitor calcium levels, as hypocalcemia may induce or worsen movement disorders 5, 11