Subcutaneous Olanzapine for Hyperactive or Mixed Delirium in Patients with Advanced Cancer: A Preliminary Study

Abstract 

Context

Oral olanzapine is effective in controlling agitation in patients with delirium, but often, parenteral administration is necessary. Intramuscular (IM) olanzapine is approved for managing agitation in schizophrenia, but this route is inappropriate for terminally ill patients.

Objectives

The purpose of this pilot study was to determine the safety and tolerability of subcutaneous (SC) olanzapine in the management of hyperactive or mixed delirium in patients with advanced cancer.

Methods

We conducted a prospective open-label study in patients with advanced cancer who had agitated delirium (Richmond Agitation Sedation Scale [RASS] score ≥+1) that had not responded to a 10mg or higher dose of parenteral haloperidol over 24 hours. Patients received olanzapine 5mg SC every eight hours for three days and continued haloperidol for breakthrough agitation. For patients requiring more than 8mg of rescue haloperidol daily, the olanzapine dose was increased to 10mg SC every eight hours. Injection site, systemic toxicity, and efficacy (RASS score <+1 and total haloperidol dose <8mg per 24 hours on the last study day) were evaluated.

Results

Twenty-four patients received at least one olanzapine injection, and 15 (63%) completed the study. Median age of evaluable patients was 58 years (range 49–79), and 67% were males. No injection site toxicity was observed after 167 injections. Probable systemic toxic effects were observed in four patients (severe hypotension [blood pressure <90/50mmHg], paradoxical agitation, diabetes insipidus, and seizure). Efficacy was achieved in nine (37.5%) patients.

Conclusions

IM olanzapine is well tolerated subcutaneously. Further research is needed to evaluate its efficacy in controlling agitated delirium.

Key Words: Hyperactive delirium, mixed delirium, advanced cancer, olanzapine, subcutaneous route