IM olanzapine cost-effective for acute agitation in A&E departments

Intramuscular (IM) olanzapine is similarly cost-effective with a better safety profile compared with IM haloperidol for sedating patients with acute agitation in Accident and Emergency (A&E) departments, according to cost-effectiveness data from a randomized clinical trial (RCT) conducted by the University of Hong Kong (HKU) and clinical teams of six A&E departments of the Hong Kong Hospital Authority (HA).

 

“Through this research, [our] team was the first to provide the necessary evidence on comparative cost-effectiveness of the three drug options [IM olanzapine, midazolam and haloperidol] for acute agitation management in A&E departments,” noted the researchers.

 

Earlier findings from the RCT demonstrated noninferiority of IM olanzapine to haloperidol and midazolam in terms of efficacy and safety in acute agitation management in A&E settings. New data from the RCT showed that IM midazolam was associated with the lowest median total treatment cost compared with IM olanzapine and IM haloperidol (HKD 1,958.9, HKD 2,467.6 and HKD 2,504.5, respectively). [EClinicalMedicine 2021;32:100751; Value Health 2022;doi:10.1016/j.jval.2021.11.1374]

 

“The labour cost in agitation management was the main cost driver in the emergency setting [around 30–40 percent in the base case, >70 percent when excluding investigational costs], whereas unit drug cost contributed the least [around 0.5–3 percent in the base case, <10 percent excluding investigational costs],” the researchers reported.

 

IM midazolam remained dominant among the three treatments in >95 percent of the time in probabilistic sensitivity analysis, showing that it was the dominant treatment strategy economically.

 

“[However], in patients with suspected underlying psychoses, the use of antipsychotic agents for rapid sedation is generally preferred in practice over benzodiazepines [ie, midazolam] to prevent oversedation and preserve the opportunity for psychiatric follow-up and assessment,” the researchers explained.

 

Compared with IM haloperidol, IM olanzapine had a slightly lower cost (HKD 2,467.6 vs HKD 2,504.5) but slightly lower effectiveness (116.70 minutes vs 116.76 minutes of agitation-free time gained). There was no significant difference in cost-effectiveness of IM olanzapine vs IM haloperidol (incremental cost-effectiveness ratio [ICER], 667.15; 95 percent confidence interval, -770.89 to +685.90).

 

“[Haloperidol as a first-generation antipsychotic] is associated with adverse effects [AEs] including QT prolongation, dystonia, and extrapyramidal effects. In cases where the use of benzodiazepines is less desirable, IM olanzapine could be a preferred alternative over IM haloperidol since it has a more favourable AE profile [ie, a more benign cardiovascular profile and fewer extrapyramidal side effects] and is as cost-effective as IM haloperidol,” the researchers suggested.

 

“The findings serve to support formulary decisions on introducing and broadening the use of IM olanzapine for acute agitation in the emergency department. Subsequent to the [earlier] RCT findings, IM olanzapine was incorporated into local A&E clinical guidelines by the HA and added to the A&E drug formulary at the Hong Kong West Cluster,” they added. “The latest pharmacoeconomic findings are expected to drive the expanded implementation or adoption of IM olanzapine in additional HA clusters.”