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Efficacy and safety of quetiapine in critically ill patients with delirium: A prospective, multicenter, randomized, double-blind, placebo-controlled pilot study*

Devlin, John W. PharmD; Roberts, Russel J. PharmD; Fong, Jeffrey J. PharmD; Skrobik, Yoanna MD; Riker, Richard R. MD; Hill, Nicholas S. MD; Robbins, Tracey RN; Garpestad, Erik MD

doi: 10.1097/CCM.0b013e3181b9e302
Clinical Investigations

Objective: To compare the efficacy and safety of scheduled quetiapine to placebo for the treatment of delirium in critically ill patients requiring as-needed haloperidol.

Design: Prospective, randomized, double-blind, placebo-controlled study.

Setting: Three academic medical centers.

Patients: Thirty-six adult intensive care unit patients with delirium (Intensive Care Delirium Screening Checklist score ≥4), tolerating enteral nutrition, and without a complicating neurologic condition.

Interventions: Patients were randomized to receive quetiapine 50 mg every 12 hrs or placebo. Quetiapine was increased every 24 hrs (50 to 100 to 150 to 200 mg every 12 hrs) if more than one dose of haloperidol was given in the previous 24 hrs. Study drug was continued until the intensive care unit team discontinued it because of delirium resolution, therapy ≥10 days, or intensive care unit discharge.

Measurements and Main Results: Baseline characteristics were similar between the quetiapine (n = 18) and placebo (n = 18) groups. Quetiapine was associated with a shorter time to first resolution of delirium [1.0 (interquartile range [IQR], 0.5–3.0) vs. 4.5 days (IQR, 2.0–7.0; p =.001)], a reduced duration of delirium [36 (IQR, 12–87) vs. 120 hrs (IQR, 60–195; p =.006)], and less agitation (Sedation-Agitation Scale score ≥5) [6 (IQR, 0–38) vs. 36 hrs (IQR, 11–66; p =.02)]. Whereas mortality (11% quetiapine vs. 17%) and intensive care unit length of stay (16 quetiapine vs. 16 days) were similar, subjects treated with quetiapine were more likely to be discharged home or to rehabilitation (89% quetiapine vs. 56%; p =.06). Subjects treated with quetiapine required fewer days of as-needed haloperidol [3 [(IQR, 2–4)] vs. 4 days (IQR, 3–8; p = .05)]. Whereas the incidence of QTc prolongation and extrapyramidal symptoms was similar between groups, more somnolence was observed with quetiapine (22% vs. 11%; p = .66).

Conclusions: Quetiapine added to as-needed haloperidol results in faster delirium resolution, less agitation, and a greater rate of transfer to home or rehabilitation. Future studies should evaluate the effect of quetiapine on mortality, resource utilization, post-intensive care unit cognition, and dependency after discharge in a broader group of patients.

From the Northeastern University School of Pharmacy (JWD, RJR), Boston, MA; Massachusetts College of Pharmacy (JJF), Worcestor, MA; Department of Critical Care Medicine, Masionneuve Rosemont Hospital (YS, JH), Montreal, Quebec; Department of Critical Care Medicine, Maine Medical Center (RRR, TR), Portland, ME; Division of Pulmonary, Critical Care and Sleep Medicine, Tufts Medical Center (NSH, EG), Boston, MA.

Supported, in part, by the Society of Critical Care Medicine's Joseph F. Dasta Critical Care Pharmacy Research Award and an unrestricted grant from AstraZeneca Pharmaceuticals.

Dr. Riker has a patent for research from Astra Zeneca. Dr. Hill has received grant support from Hospira. The remaining authors have not disclosed any potential conflicts of interest.

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© 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins