Is Zyprexa (olanzapine) safe to use in patients with a history of seizures?

Olanzapine Use in Patients with Seizure Disorders

Olanzapine should be used with caution in patients with a history of seizures as it carries a risk of lowering seizure threshold, but it is not absolutely contraindicated in this population. 1

Risk Assessment of Olanzapine in Seizure Disorders

Olanzapine (Zyprexa) is an atypical antipsychotic medication that has been associated with seizure risk, though the incidence appears to be relatively low compared to some other antipsychotics. The FDA drug label specifically mentions seizures as a potential side effect, stating: "Seizures: Tell your doctor if you have a seizure during treatment with olanzapine tablets." 1

Evidence of Seizure Risk

Several case reports have documented seizures associated with olanzapine use:

• Cases of repetitive focal motor seizures with lingual dystonia 2
• Myoclonic status epilepticus in a patient with probable Alzheimer's disease 3
• Generalized tonic-clonic seizures even at subtherapeutic doses in elderly patients 4
• Status epilepticus in a patient receiving olanzapine and mirtazapine 5

Clinical Recommendations

Dosing Considerations

When olanzapine is deemed necessary for patients with a seizure history:

• Start with lower doses (2.5-5 mg daily) 6
• Titrate slowly while monitoring for seizure activity
• Consider once-daily dosing, preferably at bedtime 6
• Avoid rapid dose escalation

Monitoring Requirements

• Regular clinical assessment for emergence of seizure activity
• Consider EEG monitoring in high-risk patients
• Monitor for drug interactions with antiepileptic medications

Risk Factors That Increase Seizure Potential

Be particularly cautious when the following factors are present:

• Advanced age (>65 years) 4
• Cognitive impairment or dementia 3
• History of stroke 4
• Concomitant use of other medications that lower seizure threshold 5
• Metabolic disturbances

Alternative Antipsychotics

If a patient has poorly controlled epilepsy or has experienced seizures on olanzapine:

• Quetiapine may be a safer alternative among atypical antipsychotics for patients with seizure disorders 6
• Risperidone at low doses may also be considered 6
• Avoid typical antipsychotics with high seizure risk (e.g., chlorpromazine) 6

Practical Approach to Management

1. Assess seizure risk: Determine seizure history, frequency, and control with current antiepileptic regimen
2. Evaluate need for olanzapine: Consider if benefits outweigh risks
3. Start low, go slow: Begin with 2.5 mg daily if olanzapine is necessary 6
4. Monitor closely: Watch for emergence of seizure activity, especially during dose titration
5. Avoid combinations with other medications that lower seizure threshold when possible
6. Ensure adequate antiepileptic coverage: Optimize anticonvulsant therapy before starting olanzapine

Important Caveats

• The seizure risk with olanzapine appears lower than with clozapine but higher than with some other atypical antipsychotics 3
• Seizures can occur even at subtherapeutic doses in vulnerable populations 4
• Patients and caregivers should be educated about recognizing seizure activity
• Have a clear plan for what to do if seizures occur while on olanzapine

In conclusion, while olanzapine carries some risk of lowering seizure threshold, it can be used with appropriate caution in patients with a history of seizures when clinically indicated. The risk-benefit assessment should consider the severity of the psychiatric condition, seizure control, and availability of alternative treatments.