How to manage psychosis related to Madopar (Levodopa/Benserazide) in patients with Parkinson's disease?

Management of Madopar (Levodopa/Benserazide) Related Psychosis in Parkinson's Disease

For Madopar-induced psychosis in Parkinson's disease patients, the first-line approach is to reduce or eliminate the medication in a stepwise manner while adding an atypical antipsychotic such as quetiapine, starting at low doses (12.5 mg twice daily). 1, 2

Understanding Levodopa-Induced Psychosis

• Psychotic symptoms develop in 20-30% of Parkinson's disease patients receiving chronic anti-parkinsonian medications, with visual hallucinations and paranoid delusions being the most frequent manifestations 3
• Hallucinations and psychotic-like behavior typically present shortly after initiation of therapy and may be responsive to dose reduction of levodopa 1
• These symptoms can include paranoid ideation, delusions, hallucinations, confusion, disorientation, aggressive behavior, agitation, and delirium 1
• Psychotic symptoms significantly impact activities of daily living and quality of life, often burdening caregivers more than motor disabilities 3

Management Algorithm

Step 1: Eliminate Non-Medication Triggers

• Rule out other causes of psychosis such as infections, metabolic disorders, subdural hematoma, and other hallucinogenic drugs 3
• Assess for delirium which may present with similar symptoms but requires different management 4

Step 2: Medication Adjustment

1. Reduce anti-parkinsonian medications in the following order:

   • First: Anticholinergics, amantadine, and selegiline 3
   • Second: Dopamine agonists 3
   • Third: Levodopa/benserazide (Madopar) 3

2. Dosage reduction strategy:

   • Reduce medications to the point of improving psychotic symptoms without drastically worsening motor symptoms 3
   • Consider switching from standard Madopar to controlled-release formulation (Madopar HBS) which may provide more stable plasma levels 5
   • Be aware that equivalent levodopa dosage may need to be increased by approximately 56% when switching to Madopar HBS 5

Step 3: Antipsychotic Medication

When medication adjustments fail to sufficiently alleviate psychotic symptoms:

1. First-line antipsychotics (atypical):

   • Quetiapine: Start at 12.5 mg twice daily; maximum: 200 mg twice daily 4, 2

     • Approximately 80% of PD patients show improvement in psychosis with quetiapine 2
     • More sedating; monitor for transient orthostasis 4
     • Mean effective dose: 54 mg per day 2

   • Risperidone: Initial dosage: 0.25 mg per day at bedtime; maximum: 2-3 mg per day 4

     • Use low doses; extrapyramidal symptoms may occur at 2 mg per day 4

   • Olanzapine: Initial dosage: 2.5 mg per day at bedtime; maximum: 10 mg per day 4

     • Generally well tolerated but may worsen parkinsonism 4

2. Second-line options (typical antipsychotics):

   • Should be avoided if possible due to significant risk of extrapyramidal side effects 4
   • Associated with risk of irreversible tardive dyskinesia (can develop in 50% of elderly patients after 2 years of continuous use) 4

Special Considerations

• Patients with dementia: More susceptible to motor worsening with antipsychotic treatment 2

  • All patients who experienced motor worsening on quetiapine in one study were in the dementia group 2
  • Careful monitoring of motor symptoms is essential in this population 2

• Monitoring requirements:

  • Regular assessment of motor symptoms using standardized scales (e.g., UPDRS motor score) 2
  • Periodic evaluations of hepatic, hematopoietic, cardiovascular, and renal function during extended therapy 1

• Family support:

  • Include families in the treatment plan and provide education about the nature of the problem 4
  • Provide emotional support and practical advice to families who are usually in crisis 4

Pitfalls and Caveats

• Avoid abrupt withdrawal of Madopar as it can precipitate severe worsening of parkinsonian symptoms 3
• Typical antipsychotics (haloperidol, fluphenazine) should be avoided as they can significantly worsen motor symptoms 4
• Benzodiazepines should be used cautiously as they can lead to tolerance, addiction, cognitive impairment, and paradoxical agitation in about 10% of patients 4
• Be aware that patients with a major psychotic disorder should not be treated with levodopa/benserazide due to risk of exacerbating psychosis 1
• Monitor for impulse control disorders (gambling, increased sexual urges, uncontrolled spending) which may develop with dopaminergic medications 1