Therapeutic Evidence - Olanzepine
Skrobik et al. 2004. Olanzapine vs haloperidol: treating delirium in a critical care setting. Intensive Care Med; 30:444-449.
Study Objectives
- To compare the safety and estimate the response profile of olanzapine to haloperidol in the treatment of delirium in the critical care setting.
Methods
- Design - prospective, randomized, open-labeled, gold-standard (haloperidol) controlled
- Blinding - Un-blinded
- Follow-up Period - 5 days
- Setting - tertiary care university-affiliated critical care unit (Maisonneuve-Rosemont Hospital, Montreal QC)
- Participants - (N= 73 subjects) - All patients aged 18-75 presenting to the ICU for greater than 24hrs were screened using the ICDSC 3x daily for delirium. Patients with altered mental state, who were referred to a physician for confirmed diagnosis using the DSM-IV criteria. Detailed inclusion and exclusion criteria was provided.
- Allocation - Randomization to either treatment based on an even/odd day basis for haloperidol or olanzapine. Groups were unevenly distributed (haloperidol - N = 45 vs olanzapine - N = 28). No correction was made.
- Intervention - Patients either received haloperidol IV (2.5-5mg every 8 hours) or olanzapine (5mg daily) twice daily. (NOTE: patients >60 yrs received either haloperidol 0.5-1mg or olanzapine) Subsequent titration was based on clinical judgement. Benzodiazepine use was allowed for adjunct therapy and amounts used were recorded.
- Outcomes Assessed: Patient delirium severity and benzodiazepine use over 5 days.
Results
- Mean daily dose administered: haloperidol 6.5mg vs olanzapine 4.54 mg.
- No significant difference in reduction of delirium scores over time between patients treated with haloperidol vs olanzapine (ANOVA time effect p= 0.02, group effect p=0.83, interaction effect p=0.64).
- Benzodiazepine use - ANOVA showed no statistical significance at any 5 measurement times between groups (interaction effect p=0.94, group effect p=0.9), however, there was a significant time effect reflecting a decrease in required dosages required over time in both groups (p=0.02)
Conclusions
"Olanzepine is a safe alternative to haloperidol in delirious critical care patients, and may be of particular interest in patients whom haloperidol is contraindicated."
Limitations
The main limitation of this trial was the uneven distribution between the the two treatment group. This was due to the lack of correction of the odd/even day randomization, which was admittedly chosen for convenience. The lack of blinding of the assessing physician and nurses may have also influenced subsequent administration of study medications or other medications. The small sample size also brings into question whether this study was adequately powered to show a difference in treatment groups.