Can I use Zyprexa (olanzapine) and Remeron (mirtazapine) together for treating agitation?

Using Zyprexa (Olanzapine) and Remeron (Mirtazapine) Together for Agitation

Yes, you can use Zyprexa (olanzapine) and Remeron (mirtazapine) together for treating agitation, as they have complementary mechanisms and can be effective when combined for severe agitation. This combination leverages olanzapine's antipsychotic properties with mirtazapine's sedating effects.

Medication Properties and Rationale

Olanzapine (Zyprexa)

• Mechanism: Atypical antipsychotic that works as a serotonin-dopamine receptor antagonist 1
• Dosing for agitation:
  • Initial: 2.5 mg at bedtime
  • Maximum: 10 mg daily (usually divided twice daily) 1
• Benefits: Generally well-tolerated, effective for controlling problematic delusions, hallucinations, and severe psychomotor agitation 1
• Onset of action: 20-30 minutes (IM), 45-60 minutes (oral) 1

Mirtazapine (Remeron)

• Mechanism: Heterocyclic antidepressant with sedating properties
• Dosing for agitation:
  • Initial: 7.5 mg at bedtime
  • Maximum: 30 mg at bedtime 1
• Benefits: Potent and well-tolerated; promotes sleep, appetite, and weight gain 1

Combination Approach

The combination of olanzapine and mirtazapine can be particularly effective because:

1. Complementary mechanisms: Olanzapine addresses psychotic symptoms and agitation through dopamine/serotonin antagonism, while mirtazapine enhances sedation and sleep quality

2. Timing strategy:

   • Administer mirtazapine at bedtime to promote sleep
   • Olanzapine can be given in divided doses (morning/evening) or at bedtime depending on sedation needs

3. Synergistic effects: The combination may provide better control of agitation than either medication alone, similar to how combination treatments with antipsychotics and other agents have shown superior results 2

Monitoring and Precautions

When using this combination, monitor for:

1. Excessive sedation: Both medications have sedating properties that may be additive

2. QTc prolongation: Olanzapine can prolong QTc interval, though less than some other antipsychotics 1

3. Metabolic effects: Both medications can cause weight gain and metabolic changes

4. Cognitive effects: In patients with traumatic brain injury or cognitive impairment, olanzapine may worsen confusion 3

5. Orthostatic hypotension: Both medications can cause this side effect

Special Considerations

• Elderly patients: Start with lower doses of both medications (olanzapine 2.5 mg, mirtazapine 7.5 mg)

• Patients with dementia: Use caution as antipsychotics carry black box warnings for increased mortality in elderly patients with dementia

• Cognitive function: Recent research suggests olanzapine may prolong post-traumatic amnesia in TBI patients 3, so consider this in patients with cognitive impairment

Alternative Approaches

If this combination is ineffective or poorly tolerated:

1. Antipsychotic + benzodiazepine: Combination of olanzapine with lorazepam or midazolam is frequently recommended for acute agitation 1

2. Antipsychotic + antihistamine: Combinations like risperidone with diphenhydramine or haloperidol with diphenhydramine 1

3. Alternative atypical antipsychotics: Risperidone or quetiapine may be considered if olanzapine is not tolerated

Remember that medication should be part of a comprehensive approach that includes identifying and addressing triggers of agitation when possible.