Therapeutic Evidence - Quetiapine
Devlin et al. 2010. Efficacy and safety of quetiapine in critically ill patients with delirium: a prospective, multicentre, randomized, double-blind, placebo controlled study. Crit Care Med; 38(2)416-427.
Study Objectives
- To compare the efficacy and safety of scheduled quetiapine to placebo for the treatment of delirium in critically ill patients requiring as needed haloperidol.
Methods
- Design - prospective, randomized, double-blind, placebo-controlled
- Blinding - Both patients and assessors were blinded. Both placebo and quetiapine were given as an identical tablet through NG-tube.
- Follow-up Period - 10 days or until discharge.
- Setting - Three academic medical centres.
- Participants - (N= 36 subjects) - Adult intensive care unit patients with delirium based on a ICDSC score >4 tolerating enteral nutrition, and without any complicating neurological condition. Detailed study inclusion and exclusion criteria were provided.
- Allocation - Randomization was computer generated and a different randomization schedule was used at each site. (Equal distribution = 18 in each group, with no statistically significant difference in baseline characteristics)
- Intervention - Patients randomized to received quetiapine (5mg every 12hrs) or placebo. As needed haloperidol IV (1-10mg q2h prn) was permitted in both groups. Quetiapine or placebo dose was increased by 50mg every 12hrs on a daily basis if the subject received more than one dose of haloperidol in the previous 24hrs.
- Outcomes Assessed: PRIMARY = Time to first resolution of delirium (defined as the time in hours from administration of first dose until delirium no longer present, ICDSC<3). SECONDARY = total hours in delirium during study, total hours spent deeply sedated (SAS <2) or agitated (SAS >5).
Results
- Time (hrs) of study drug administration was significantly less for quetiapine vs placebo (102 vs 186, p=0.4).
- Time (hrs) in delirium was significantly less for quetiapine vs. placebo (36 vs 120, p=0.006).
- Time (hrs) spent agitated (SAS >5) was significantly less for quetiapine vs. placebo (6 vs 36, p=0.02)
- Time (hrs) spent deeply sedated (SAS <2) was not significantly between quetiapine vs. placebo groups (0 vs. 0, p=0.54)
Conclusions
Quetiapine added to as-needed haloperidol results in faster delirium resolution and less agitation.
Limitations
This trial had very good internal validity and was statistically powered to show a difference in the primary end point of time to first resolution. However, there was inadequate power to reliably detect differences in safety outcomes. The authors state that multiple analyses that were completed may contribute to a Type-1 error. The authors indicate that the study results should be taken as a pilot study. Overall, however, the fact that the study procedure was sound and their patient population was reflective of the typical ICU patient, quetiapine should be considered as a potential therapeutic option for the treatment of delirium.