title: Efficacy and safety of quetiapine in critically ill patients with delirium: a prospective, multicenter, randomized, double-blind, placebo-controlled pilot study.
abstract: 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.
  
  
  METHODS
  Prospective, randomized, double-blind, placebo-controlled study.
  
  
  METHODS
  Three academic medical centers.
  
  
  METHODS
  Thirty-six adult intensive care unit patients with delirium (Intensive Care Delirium Screening Checklist score > or = 4), tolerating enteral nutrition, and without a complicating neurologic condition.
  
  
  METHODS
  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 > or = 10 days, or intensive care unit discharge.
  
  
  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 > or = 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.
authors.affiliation: Northeastern University School of Pharmacy, Boston, MA, USA. j.devlin@neu.edu
authors.forename: John W
authors.initials: JW
authors.lastname: Devlin
authors.forename: Russel J
authors.initials: RJ
authors.lastname: Roberts
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Fong
authors.forename: Yoanna
authors.initials: Y
authors.lastname: Skrobik
authors.forename: Richard R
authors.initials: RR
authors.lastname: Riker
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Hill
authors.forename: Tracey
authors.initials: T
authors.lastname: Robbins
authors.forename: Erik
authors.initials: E
authors.lastname: Garpestad
mesh_terms: D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003422:Critical Care; D003693:Delirium / Q000188:drug therapy*; D003987:Dibenzothiazepines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006220:Haloperidol / Q000627:therapeutic use; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D000069348:Quetiapine Fumarate
chemical_list: D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate; D006220:Haloperidol