What is the role of olanzapine in managing chorea?

Olanzapine in the Management of Chorea

Olanzapine is an effective treatment option for chorea, particularly beneficial in Huntington's disease, with recommended starting doses of 2.5-5 mg daily and potential benefit from higher doses (up to 30 mg) in severe cases. 1, 2

Mechanism and Clinical Efficacy

• Olanzapine works by antagonizing multiple receptors involved in movement disorders, particularly dopamine D2 receptors, which helps control choreatic movements 1
• In severe chorea, high-dose olanzapine (up to 30 mg daily) has demonstrated significant improvement in motor symptoms, allowing patients to regain functional abilities such as eating and walking independently 2
• Olanzapine has shown comparable efficacy to tetrabenazine for controlling Huntington's chorea, with patients on olanzapine showing a slower annual worsening of motor symptoms (3.20 points) compared to matched tetrabenazine groups (5.70 points) 3

Dosing Protocol and Titration

• Start with 2.5-5 mg daily, with gradual upward titration based on clinical response and tolerability 1
• Lower starting doses should be used in elderly patients or those with hepatic impairment 1
• In cases of severe chorea that doesn't respond to standard doses, higher doses up to 30 mg daily may be considered, as significant improvement has been documented at this dosage 2, 4
• For optimal management of sleep disturbances, the highest daily dose can be administered at night to leverage the sedative effects 5

Clinical Applications Beyond Huntington's Disease

• Olanzapine may be beneficial in chorea associated with:
  • Antiphospholipid antibody syndrome 1
  • Systemic lupus erythematosus with neuropsychiatric manifestations 1
• Particularly valuable in patients with concurrent weight loss and chorea, as olanzapine can help address both symptoms simultaneously 5

Monitoring and Side Effect Management

• Regular monitoring is essential for:
  • Extrapyramidal symptoms (though risk is lower than with typical antipsychotics) 1
  • Metabolic effects (weight gain, hyperglycemia, dyslipidemia) 6
  • Sedation and orthostatic hypotension 6
  • QTc prolongation, especially when combined with other medications affecting cardiac conduction 1

Important Precautions and Contraindications

• Avoid combining olanzapine with benzodiazepines when possible, as fatalities have been reported with this combination 1, 6, 7
• Use with caution in:
  • Patients with Parkinson's disease or dementia with Lewy bodies due to increased risk of extrapyramidal symptoms 1, 6
  • Elderly patients, particularly those with dementia-related psychosis (boxed warning for increased mortality) 6
  • Patients with cardiovascular disease due to potential effects on cardiac conduction 6
  • Patients with severe hepatic impairment 6

Combination Therapy Approaches

• When using olanzapine with other medications, be vigilant for additive side effects, particularly excessive sedation and extrapyramidal symptoms 1
• In Huntington's disease with severe chorea, some clinicians combine antidopaminergic drugs with different mechanisms (e.g., a postsynaptic agent like tiapride with a presynaptic agent like tetrabenazine) 5
• When combining olanzapine with other antipsychotics, use lower doses of both medications to minimize adverse effects 6

Clinical Pearls

• Olanzapine can be particularly beneficial when chorea co-occurs with psychiatric symptoms or weight loss 5
• Myoclonus in Huntington's disease is often misdiagnosed as chorea but may respond better to valproic acid than to antidopaminergic medications like olanzapine 8
• The sedative effects of olanzapine can be therapeutically leveraged by administering the highest daily dose at night to improve sleep disturbances 5