What's the next step for a patient with ongoing agitation after receiving 25 mg of Thorazine (chlorpromazine) intramuscularly (IM), who cannot receive Haldol (haloperidol) or Ativan (lorazepam)?

Next PRN Medication for Refractory Agitation After Thorazine

Give intramuscular olanzapine 10 mg IM as the next PRN medication for this patient with persistent agitation after chlorpromazine, who cannot receive haloperidol or lorazepam. 1, 2

Rationale for Olanzapine IM

Olanzapine IM is the optimal choice because it provides rapid control of agitation (within 15-30 minutes), has superior efficacy compared to haloperidol, and avoids the contraindicated medications. 3, 4

• Olanzapine 10 mg IM is specifically recommended by the American College of Emergency Physicians for non-cooperative patients requiring parenteral medication 1
• In head-to-head trials, olanzapine IM achieved adequate sedation in significantly more patients at 15 minutes compared to haloperidol (18-20% greater proportion adequately sedated) 3
• Olanzapine has minimal extrapyramidal side effects and the least QTc prolongation (only 2 ms) among antipsychotics, making it the safest cardiac profile 2

Dosing Protocol

Administer olanzapine 10 mg IM now, then reassess in 15-30 minutes. 1, 3

• If inadequate response after 2 hours, you may give an additional 2.5-5 mg IM 1
• Maximum daily dose is 30 mg, but most patients respond to 10-20 mg total 4
• Transition to oral olanzapine 2.5-10 mg daily once acute agitation resolves 1, 2

Alternative Options (If Olanzapine Unavailable)

If olanzapine is not available, consider these alternatives in order of preference:

Second choice: Ziprasidone 20 mg IM 1, 2

• Rapid onset within 30 minutes with notably absent extrapyramidal symptoms 2
• Can repeat 10 mg IM after 2 hours or 20 mg IM after 4 hours if needed 3
• Caution: Causes more QTc prolongation (5-22 ms) than olanzapine; avoid if cardiac disease present 2

Third choice: Midazolam 2.5-5 mg IM 1

• Most rapid sedation (superior to all antipsychotics at 15 minutes) but purely sedating without antipsychotic effect 3
• Major caveat: 10% risk of paradoxical agitation, especially in elderly or young patients 2
• Unpredictable duration of CNS depression 2

Critical Safety Considerations

Do NOT combine olanzapine IM with any benzodiazepine - this combination has been associated with fatalities and severe respiratory depression 4

• Monitor blood pressure closely after any IM antipsychotic, as hypotension can occur (though rare at 0.5% incidence) 3
• Reassess the patient every 15 minutes during the first hour to determine if additional medication is needed 1
• Obtain baseline ECG if cardiac risk factors present, as chlorpromazine already on board may have QTc effects 2

Why Not Repeat Chlorpromazine?

The FDA label indicates chlorpromazine 25 mg IM can be repeated in 1 hour if no hypotension occurred, with subsequent doses up to 400 mg every 4-6 hours in severe cases 5. However, switching to an atypical antipsychotic is preferred over escalating typical antipsychotics because:

• Atypical antipsychotics provide comparable efficacy with significantly fewer extrapyramidal side effects 2
• Chlorpromazine has already failed at the initial dose, suggesting need for a different mechanism 1
• Guidelines recommend atypical antipsychotics as preferred first-line agents when available 2