Journal of the Louisiana State Medical Society
Psychopharmacological Treatment of Delirium: Does Earlier Treatment and Scheduled Dosing Improve Outcomes?
Ashley Weiss, DO, MPH; Michael S. Scheeringa, MD, MPH
Purpose: The goals of this study were to examine how dosing strategies and timeliness of antipsychotic medication initiation would affect delirium duration. Methods: This is a retrospective paper and electronic record review of patients in an academic hospital who had been diagnosed with delirium. Forty-two patients met inclusion criteria. Quantitative and qualitative data on the course of delirium was gathered, as well as important demographic and medical variables. Results: There were no significant differences in duration of deliriumbetween the scheduled and PRN groups using survival analysis, although the test was marginally significant (log rank test, p<0.06). Those who re- ceived treatment within 24 hours of recognition had significantly shorter durations of delirium compared to those who began treatment after 24 hours (log rank test, p<0.006). Conclusion: These data suggest that early psychopharmacological treatment of delirium can reduce duration. Future research needs to investigate prompt and scheduled medication dosing strategies for treatment of delirium symptoms.
INTRODUCTION Delirium is a central nervous system manifestation of a systemic disease process that has crossed the blood brain barrier. Delirium occurs at rates ranging from 10%-30% of all general hospital admissions, leads to longer hospital stays and higher mortality, and is associated with increased functional decline andmorbidity, especially if unrecognized and undertreated. 1 Delirium risks are cumulative, and with each day delirious, there is an increased risk of prolonged hospitalization and 10% increased risk of death. 2 Delirium is independently associatedwith higher ICU costs ($22,346 vs $13,332, respectively) and hospital costs ($41,836 vs $27,106, respectively) compared to those without delirium. 3 There has been increased attention to early recogni- tion and treatment of this disorder. Evidence indicates that prompt and scheduled medication treatment is most effec- tive; 4 however, evidence is scarce. Prompt treatment may be important because deliriumseems to result froma cascade of interacting processes, beginning with a physical stress and/ or trauma and leading to systemic inflammation, compro- mised oxidative metabolism; and resulting in cellular dam- age and neurotransmitter disruptions. The cellular damage has been thought to be the result of dopamine-induced cell death, 5 and in a recent study, protein markers of brain dam- age were elevated in the blood and CSF of delirious patients
following orthopedic surgery for hip fracture. 6 Treatment strategies for delirium are still controversial. There is no approved treatment from the Federal Drug Administration, and the optimal doses and regimen have not been defined in clinical trials. There is evidence that treatment of delirium with antipsychotic medications is ef- fective andmay shorten time delirious and decrease hospital stays. Both typical antipsychotics (e.g., haloperidol) and newer atypical antipsychotics (aripiprazole, olanzapine, and risperidone) have shown preliminary effectiveness in controlled 7 and uncontrolled studies. 8,9 In the only known placebo-controlled study, a randomized trial of 101 end stage cancer patients, there were no differences in duration of delirium until death between haloperidol, ziprasidone, and placebo. 10 However, the severe, terminal status of this populationmakes generalization of the results problematic. In a review of the literature by Campbell et al., 11 the existing controlled studies compared pharmacologic intervention to no pharmacologic intervention (as opposed to placebo) in the treatment of delirium in hospitalized adults. Antipsy- chotic medications showed the greatest effectiveness and appeared to decrease the severity and duration. 11 One study has examined scheduled antipsychotic dosing in the treatment of delirium. Maldonado and col- leagues (2003) followed patients prospectively and found that a protocol used by the psychosomatic medicine service
242 J La State Med Soc VOL 166 November/December 2014
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