What medication is used to treat agitation in Parkinson's disease (PD)?

Medication Management for Agitation in Parkinson's Disease

Quetiapine is the preferred medication for treating agitation in Parkinson's disease due to its effectiveness in controlling psychosis without significantly worsening motor symptoms. 1, 2

First-Line Treatment: Atypical Antipsychotics

Quetiapine

• Initial dosage: 12.5 mg twice daily; can be titrated up to a maximum of 200 mg twice daily 3
• Most effective atypical antipsychotic for PD patients with minimal impact on motor function 2
• Common side effects include sedation and orthostatic hypotension, but these are often manageable 1
• Multiple studies involving over 200 Parkinson's disease patients suggest quetiapine is well tolerated and effective for controlling psychosis and agitation 1

Clozapine

• Initial dosage: 6.25-12.5 mg at bedtime; can be gradually increased as needed 4
• The only atypical antipsychotic with confirmed benefit in controlled trials without worsening parkinsonism 4
• Requires regular blood monitoring due to risk of agranulocytosis 1
• Common side effects include sedation, orthostatic hypotension, and sialorrhea 1
• May actually improve tremor in some PD patients 4

Medications to Avoid or Use with Caution

Risperidone

• Poorly tolerated in PD patients due to significant worsening of motor symptoms 4
• Should be used only as a last resort when other options have failed 4

Olanzapine

• Better tolerated than risperidone but still worsens motor function in the majority of PD patients 4
• Initial studies showed promise, but subsequent reports demonstrated deleterious effects on motor function 1

Typical Antipsychotics

• Should be avoided in PD patients as they block dopamine receptors and significantly worsen motor symptoms 3, 1
• Examples include haloperidol, fluphenazine, and thiothixene 3

Treatment Algorithm

1. First step: Evaluate for and treat any underlying medical causes of agitation (infection, metabolic disturbances, etc.) 1

2. Second step: Review and optimize anti-Parkinson medications

   • Simplify medication regimen if possible 4
   • Consider reducing medications with highest psychotomimetic potential 4
   • Order of reduction: anticholinergics first, then selegiline, dopamine agonists, amantadine, COMT inhibitors, and finally levodopa if necessary 4

3. Third step: If agitation persists despite medication optimization, initiate quetiapine

   • Start at low dose (12.5 mg daily or twice daily) 2
   • Titrate slowly based on response and tolerability 2
   • Average effective dose is approximately 40 mg daily 2

4. Fourth step: If quetiapine is ineffective or not tolerated, consider clozapine

   • Requires regular blood monitoring 1
   • Start at very low dose (6.25 mg) and titrate slowly 4

Monitoring and Follow-up

• Assess for improvement in psychiatric symptoms using standardized scales when possible 2
• Monitor for worsening of motor symptoms using UPDRS or clinical examination 2
• Watch for common side effects: sedation, orthostatic hypotension, and confusion 1, 2
• Adjust dosage to find the minimum effective dose that controls agitation without compromising motor function 4

Special Considerations

• Sedating properties of quetiapine and clozapine can be beneficial for nighttime dosing in patients with sleep disturbances 1
• Benzodiazepines should be used cautiously in elderly PD patients due to risk of cognitive impairment, falls, and paradoxical agitation 3
• Cholinesterase inhibitors may help alleviate psychosis in some PD patients with cognitive impairment 1
• For severe, treatment-resistant cases, electroconvulsive therapy may be considered 1