What are the recommendations for combining Zyprexa (olanzapine) and Ativan (lorazepam)?

Combination of Zyprexa (Olanzapine) and Ativan (Lorazepam)

The combination of olanzapine and lorazepam is generally safe and effective for acute agitation in most patients, but should be avoided in alcohol-intoxicated patients due to risk of respiratory depression.

Primary Recommendation for Acute Agitation

For cooperative patients with acute agitation, the combination of oral lorazepam 2 mg plus an atypical antipsychotic (such as olanzapine 2.5-5 mg) is recommended as first-line therapy. 1, 2

• This combination produces similar improvement to haloperidol plus lorazepam but with significantly fewer extrapyramidal side effects 2, 3
• The combination reduces extrapyramidal symptoms compared to antipsychotics alone (NNH 2, meaning for every 2 patients treated with combination therapy, one fewer will develop extrapyramidal symptoms) 3

Critical Safety Considerations

Alcohol Intoxication - The Key Contraindication

In patients with known alcohol ingestion, avoid the olanzapine + lorazepam combination due to significantly lower oxygen saturations. 4

• In alcohol-positive patients, olanzapine + benzodiazepines were associated with lower oxygen saturations than haloperidol + benzodiazepines 4
• In alcohol-negative patients, the combination showed no increased risk of respiratory depression 4
• For intoxicated patients, consider haloperidol alone, haloperidol + benzodiazepines, or olanzapine alone instead 4

Hypotension Risk

The combination does not appear to increase hypotension risk beyond either agent alone:

• No patients in the olanzapine + benzodiazepine group developed hypotension in comparative studies 4
• Monitor blood pressure before and after administration, particularly in elderly patients 1

Dosing Algorithm

For Acute Agitation in Non-Intoxicated Patients:

Initial approach:

• Lorazepam 2 mg PO + Olanzapine 2.5-5 mg PO for cooperative patients 1, 2
• May repeat olanzapine after 2 hours if needed 2

For elderly or frail patients:

• Reduce olanzapine to 2.5 mg PO 5, 1
• Consider lorazepam 1 mg instead of 2 mg

For patients with hepatic impairment:

• Start with olanzapine 2.5 mg with caution 1
• Reduce subsequent doses as needed

Monitoring Requirements

Monitor the following parameters every 5-15 minutes during the first hour: 6

• Oxygen saturation (especially critical if any suspicion of alcohol use)
• Blood pressure (for orthostatic hypotension)
• Level of sedation
• Respiratory rate

When to Use Alternative Strategies

Choose olanzapine alone (without lorazepam) if: 2, 4

• Patient has consumed alcohol or other CNS depressants
• Patient has respiratory compromise
• Patient has severe hepatic impairment

Choose lorazepam alone if: 6

• Agitation is likely due to alcohol or benzodiazepine withdrawal (lorazepam is therapeutic, not just symptomatic)
• Patient has history of substance use disorder with unknown current intoxication status

Choose haloperidol + lorazepam instead if: 4

• Patient is alcohol-intoxicated but requires combination therapy
• Cardiac disease is present and QTc prolongation is a concern (though olanzapine has minimal QTc effects at 2 ms) 2

Advantages of This Combination

• Olanzapine is generally well-tolerated with the least QTc prolongation among antipsychotics (only 2 ms mean prolongation) 2
• The combination provides faster sedation than monotherapy 6
• Significantly lower risk of extrapyramidal symptoms compared to typical antipsychotics 5, 2, 3
• Lorazepam serves as a useful adjunct to antipsychotic therapy 5

Common Pitfalls to Avoid

• Never assume a patient denying alcohol use is alcohol-negative - consider toxicology screening to guide treatment, as patient self-report may be unreliable 6
• Do not use lorazepam as monotherapy for primary psychotic agitation - it is an adjunct, not a single-agent antipsychotic 5
• Watch for oversedation in elderly patients - both agents cause sedation, and the effect is additive 1
• Do not exceed olanzapine 10 mg/day in divided doses for ongoing management 5