Olazapine Not More Effective Than Haloperidol for Delirium in Patients With Advanced Cancer
By Brian Hoyle
SAN DIEGO -- October 31, 2017 -- The first-generation antipsychotic drug haloperidol and the second-generation drug olanzapine seem to be equally effective in treating delirium in patients with advanced cancer, according to a study presented here at the 2017 ASCO Palliative Care in Oncology Symposium.
“Olanzapine is not superior to haloperidol with regard to efficacy and overall incidence of grade ≥3 adverse events for treating delirium symptoms in hospitalised patients with advanced cancer,” said Maurice van der Vorst, VU University Medical Center, Cancer Center Amsterdam, The Netherlands, on October 27.
This analysis of the study (NCT01539733) conducted at 6 sites in the Netherlands included 100 of a planned 200 patients with advanced cancer and delirium enrolled between January 2010 and June 2016. The patients were randomised to receive olanzapine (n = 50) or haloperidol (n = 50).
The patients had displayed a Delirium Observation Screening Scale score ≥3 and a Delirium Rating Scale-Revised-98 (DRS-R-98) total score ≥17.75.
The primary endpoint was the delirium response rate (DRR), which was the proportion of patients with a DRS-R-98 total severity score of <15.25 who displayed a score reduction of ≥4.5 at either day 7 of treatment or the end of the study. Secondary endpoints included the time before a response to treatment was evident, adverse events, and delirium-related distress.
The 2 arms were comparable at baseline in regard to age, DRS-R-98 score, type of delirium, prevalence of medicinal opioid use, use of benzodiazepines and neurotrophic pain medication, and the reasons for hospitalisation.
The scheduled interim analysis revealed comparable DRRs of 45% for olanzapine (95% confidence interval [CI], 31.0-58.8) and 57% for haloperidol (95% CI, 43.3-71.0; P = .22). The mean time to recovery was longer with olanzapine than with haloperidol (4.5 ± 0.7 vs 2.8 ± 0.5 days), although the difference was not significant (P = .20).
The frequency of grade ≥3 adverse events, including sedation, tremors, rigidity, dizziness, and cardiac abnormality, was 10% for patients receiving olanzapine and 20% for those receiving haloperidol (odds ratio, 0.44; 95% CI, 0.14-1.40; P = .16). The mean distress levels were 2.1 ± 1.4 and 2.9 ± 1.2 in the olazapine and haloperidol arms, respectively (P = .80).
“No difference in efficacy and side effect profile was observed between haloperidol [and] olanzapine treatment for delirium in patients with advanced cancer,” concluded Dr. van der Vorst.
At the interim analysis, the researchers determined that the likelihood that the data would reach superiority for olanzapine was remote and ended the trial. The study was powered to detect a 25% improvement in DRR in the olanzapine-treated patients.
Haloperidol remains the status quo treatment for delirium in these patients.
[Presentation title: Efficacy and Side Effect Profile of Olanzapine Versus Haloperidol for Symptoms of Delirium in Hospitalized Patients With Advanced Cancer: A Multicenter, Investigator-Blinded, Randomized, Controlled Trial (RCT).Abstract 231]