title: Impact of quetiapine on resolution of individual delirium symptoms in critically ill patients with delirium: a post-hoc analysis of a double-blind, randomized, placebo-controlled study.
abstract: BACKGROUND
  We hypothesized that delirium symptoms may respond differently to antipsychotic therapy. The purpose of this paper was to retrospectively compare duration and time to first resolution of individual delirium symptoms from the database of a randomized, double-blind, placebo-controlled study comparing quetiapine (Q) or placebo (P), both with haloperidol rescue, for critically ill patients with delirium.
  
  
  METHODS
  Data for 10 delirium symptoms from the eight-domain, intensive care delirium screening checklist (ICDSC) previously collected every 12 hours were extracted for 29 study patients. Data between the Q and P groups were compared using a cut-off P-value of ≤ 0.10 for this exploratory study.
  
  
  RESULTS
  Baseline ICDSC scores (5 (4 to 7) (Q) vs 5 (4 to 6)) (median, interquartile range (IQR)) and % of patients with each ICDSC symptom were similar in the two groups (all P > 0.10). Among patients with the delirium symptom at baseline, use of Q may lead to a shorter time (days) to first resolution of symptom fluctuation (4 (Q) vs. 14, P = 0.004), inattention (3 vs. 8, P = .10) and disorientation (2 vs. 10, P = 0.10) but a longer time to first resolution of agitation (3 vs. 1, P = 0.04) and hyperactivity (5 vs. 1, P = 0.07). Among all patients, Q-treated patients tended to spend a smaller percent of time with inattention (47 (0 to 67) vs. 78 (43 to 100), P = 0.025), hallucinations (0 (0 to 17) vs. 28 (0 to 43), P = 0.10) and symptom fluctuation (47 (19 to 67) vs. 89 (33 to 00), P = 0.04] and there was a trend for Q-treated patients to spend a greater percent of time at an appropriate level of consciousness (26% (13 to 63%) vs. 14% (0 to 33%), P = 0.17].
  
  
  CONCLUSIONS
  Our exploratory analysis suggests that quetiapine may resolve several intensive care unit (ICU) delirium symptoms faster than the placebo. Individual symptom resolution appears to differ in association with the pharmacologic intervention (that is, P vs Q, both with as needed haloperidol). Future studies evaluating antipsychotics in ICU patients with delirium should measure duration and resolution of individual delirium symptoms and their relation to long-term outcomes.
authors.affiliation: Northeastern University School of Pharmacy, 360 Huntington Avenue, Mugar 206, Boston, MA 02115, USA. j.devlin@neu.edu
authors.forename: John W
authors.initials: JW
authors.lastname: Devlin
authors.forename: Yoanna
authors.initials: Y
authors.lastname: Skrobik
authors.forename: Richard R
authors.initials: RR
authors.lastname: Riker
authors.forename: Eric
authors.initials: E
authors.lastname: Hinderleider
authors.forename: Russel J
authors.initials: RJ
authors.lastname: Roberts
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Fong
authors.forename: Robin
authors.initials: R
authors.lastname: Ruthazer
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Hill
authors.forename: Erik
authors.initials: E
authors.lastname: Garpestad
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D016638:Critical Illness; D003693:Delirium / Q000188:drug therapy*; D003987:Dibenzothiazepines / Q000627:therapeutic use*; D004311:Double-Blind Method; D006220:Haloperidol / Q000627:therapeutic use; D006801:Humans; D010919:Placebos; D000069348:Quetiapine Fumarate; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D010919:Placebos; D000069348:Quetiapine Fumarate; D006220:Haloperidol