What is the role of olanzapine in managing chorea?

Olanzapine in the Management of Chorea

Olanzapine is an effective treatment option for chorea, particularly in severe cases, with evidence showing significant reduction in choreatic movements at doses of 10-30 mg daily. 1, 2

Mechanism and Efficacy

• Olanzapine is an atypical antipsychotic that antagonizes multiple receptors involved in movement disorders, including dopamine D2 receptors, which helps control choreatic movements 3
• High-dose olanzapine (up to 30 mg daily) has demonstrated remarkable efficacy in severe chorea, with rapid improvement in symptoms within days of initiation 1
• In Huntington's disease-related chorea, olanzapine has shown significant improvement in most subscores of the Unified Huntington's Disease Rating Scale (UHDRS), including fine motor tasks 2
• Recent analysis from the Enroll-HD database suggests that olanzapine may be comparable to tetrabenazine in controlling Huntington's chorea, with potentially less worsening of total motor scores over time 4

Dosing Considerations

• Starting doses typically range from 2.5-5 mg daily, with gradual titration based on response and tolerability 3
• For severe chorea, higher doses (up to 30 mg daily) may be required for optimal symptom control 1, 2
• Lower starting doses should be considered in elderly patients or those with hepatic impairment 3
• The sedative effects of olanzapine can be utilized advantageously by administering the highest daily dose at night to improve sleep disturbances that often accompany chorea 5

Clinical Applications Beyond Huntington's Disease

• Olanzapine may be beneficial in chorea associated with antiphospholipid antibodies/syndrome, though evidence is limited 6
• In systemic lupus erythematosus with neuropsychiatric manifestations, olanzapine can be considered for management of chorea, especially when other symptoms like weight loss are present 6, 5

Combination Therapy Approaches

• In severe chorea, combining olanzapine (a postsynaptic dopamine antagonist) with a presynaptic agent like tetrabenazine may provide synergistic effects 5
• When using olanzapine with other medications, be cautious about additive side effects, particularly excessive sedation and extrapyramidal symptoms 3

Monitoring and Side Effect Management

• Regular monitoring for extrapyramidal symptoms, metabolic effects (weight gain, hyperglycemia, dyslipidemia), and sedation is essential 3
• Olanzapine carries a lower risk of extrapyramidal side effects compared to typical antipsychotics, making it potentially advantageous for chorea patients who may be sensitive to these effects 3, 4
• Be vigilant for QTc prolongation, especially when combining with other medications that may affect cardiac conduction 3

Special Considerations

• Avoid combining olanzapine with benzodiazepines when possible, as fatalities have been reported with this combination 7
• Use caution in patients with Parkinson's disease or dementia with Lewy bodies due to increased risk of extrapyramidal symptoms 3
• Olanzapine may be particularly beneficial in patients with chorea who also experience weight loss, as it can help with weight gain 5

Treatment Algorithm for Chorea

1. For mild to moderate chorea: Start with olanzapine 2.5-5 mg daily, titrate up based on response and tolerability 3, 2
2. For severe chorea: Consider higher doses (10-30 mg daily) with close monitoring for side effects 1, 2
3. For refractory cases: Consider combination therapy with a presynaptic agent like tetrabenazine 5
4. For chorea with concurrent psychiatric symptoms: Olanzapine may provide dual benefit for both movement disorder and psychiatric manifestations 5