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Quetiapine + haloperidol = faster resolution of ICU delirium

Clinical Question:
Does the addition of quetiapine to as-needed haloperidol improve outcomes in patients with delirium in the intensive care unit?

Bottom Line:
In intensive care unit (ICU) patients with delirium, the addition of scheduled quetiapine to as-needed haloperidol results in faster resolution of delirium, decreased time spent in delirium, and less agitation. This study was too small to detect significant differences in adverse events, if they exist. (LOE = 1b)

Reference:
Devlin JW, Roberts RJ, Fong JJ, et al. Efficacy and safety of quetiapine in critically ill patients with delirium: a prospective, multicenter, randomized, double-blind, placebo-controlled pilot study. Crit Care Med 2010;38(2):695-696.  [PMID:19915454]

Study Design:
Randomized controlled trial (double-blinded)

Funding:
Unknown/not stated

Allocation:
Concealed

Setting:
Inpatient (ICU only)

Synopsis:
In this small study, investigators evaluated medical and surgical ICU patients with a diagnosis of delirium for enrollment into the study. The majority of eligible patients were excluded because of recent antipsychotic use, inability to tolerate enteral nutrition, a primary neurologic condition, advanced liver disease, or active alcohol withdrawal. After screening 258 patients, the authors randomized -- using concealed allocation -- 36 patients to receive quetiapine 50 mg twice daily (n = 18) or matched placebo (n = 18). All patients also received intravenous haloperidol 1 mg to 10 mg every 2 hours as needed to control symptoms of delirium. If the patient required haloperidol in the previous 24 hours, the study drug was titrated up by increments of 50 mg to a maximum dose of 200 mg every 12 hours. The study drug was discontinued once the delirium had resolved, after 10 days of therapy, or at discharge from the ICU. Patients and providers were masked to treatment assignment and analysis was by intention to treat. The 2 groups were well balanced at baseline. More than 70% were on a medical ICU service and the most common ICU admitting diagnosis was sepsis with acute respiratory distress syndrome. Quetiapine therapy added to as-needed haloperidol was associated with a significantly shorter time to first resolution of delirium (1.0 day vs 4.5 days; P = .001). In addition, patients who received quetiapine spent less time in delirium (36 hours vs 120 hours; P = .006) and less time agitated (6 hours vs 36 hours; P = .02). Although there was no difference between the 2 groups in hospital mortality or in length of ICU stay or hospital stay, there was a trend in the quetiapine group toward being discharged either to home or a rehabilitation facility (89% in the quetiapine group vs 56% in the haloperidol only group; P = .06), rather than dying or being transferred to another hospital or nursing home. Although not statistically significant, more patients in the quetiapine group experienced possible drug-related adverse events, including 5 episodes of somnolence and 1 episode of hypotension.

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