Antipsychotic Medication for Prevention and Treatment of Delirium in Hospitalized Adults: A Systematic Review and Meta-Analysis

Abstract

Objectives: To evaluate the effectiveness of antipsychotic medications in preventing and treating delirium.

Design: Systematic review and meta-analysis.

Setting: PubMed, EMBASE, CINAHL, and ClinicalTrials.gov databases were searched from January 1, 1988, to November 26, 2013.

Participants: Adult surgical and medical inpatients.

Intervention: Antipsychotic administration for delirium prevention or treatment in randomized controlled trials or cohort studies.

Measurements: Two authors independently reviewed all citations, extracted relevant data, and assessed studies for potential bias. Heterogeneity was considered as chi-square P < .1 or I(2) > 50%. Using a random-effects model (I(2) > 50%) or a fixed-effects model (I(2) < 50%), odds ratios (ORs) were calculated for dichotomous outcomes (delirium incidence and mortality), and mean or standardized mean difference for continuous outcomes (delirium duration, severity, hospital and intensive care unit (ICU) length of stay (LOS)). Sensitivity analyses included postoperative prevention studies only, exclusion of studies with high risk of bias, and typical versus atypical antipsychotics.

Results: Screening of 10,877 eligible records identified 19 studies. In seven studies comparing antipsychotics with placebo or no treatment for delirium prevention after surgery, there was no significant effect on delirium incidence (OR = 0.56, 95% confidence interval (CI) = 0.23-1.34, I(2) = 93%). Using data reported from all 19 studies, antipsychotic use was not associated with change in delirium duration, severity, or hospital or ICU LOS, with high heterogeneity among studies. No association with mortality was detected (OR = 0.90, 95% CI = 0.62-1.29, I(2) = 0%).

Conclusion: Current evidence does not support the use of antipsychotics for prevention or treatment of delirium. Additional methodologically rigorous studies using standardized outcome measures are needed.

Keywords: adult; delirium; pharmacological prevention; pharmacological treatment.

Conflict of interest statement

Conflict of Interest: Dr. Neufeld has received grant funding in the past from Ornim Medical Device manufacturers and currently from Hitachi Medical Incorporated. Other authors have no conflicts of interest to declare.

© 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

Figures

Figure 1

Flow chart of study selection process

Figure 2

Forest Plots of Antipsychotic Use and Delirium Prevention, Duration and Severity Reduction Abbreviations: SD = Standard Deviation; 95% CI –95% Confidence Interval; df = degrees of freedom; MH = Mantel-Heanzel Odds Ratio IV = Inverse Variance; Random = Random Effects Model used to calculate estimate Total Number of Patients Combined for each Meta-analysis: A. n = 1,970 for Delirium Prevention B. n = 581 for Delirium Duration C. n = 464 for Delirium Severity

Figure 2

Forest Plots of Antipsychotic Use and Delirium Prevention, Duration and Severity Reduction Abbreviations: SD = Standard Deviation; 95% CI –95% Confidence Interval; df = degrees of freedom; MH = Mantel-Heanzel Odds Ratio IV = Inverse Variance; Random = Random Effects Model used to calculate estimate Total Number of Patients Combined for each Meta-analysis: A. n = 1,970 for Delirium Prevention B. n = 581 for Delirium Duration C. n = 464 for Delirium Severity

Figure 3

Forest Plots of Antipsychotic Use and Hospital and Intensive Care Unit (ICU) Length of Stay Abbreviations: SD = Standard Deviation; 95% CI – 95% Confidence Interval; df = degrees of freedom; MH = Mantel-Heanzel Odds Ratio IV = Inverse Variance; Random = Random Effects Model used to calculate estimate; Fixed = Fixed Effects Model used to calculatethe estimate. Total Number of Patients Combined for each Meta-analysis: A. n = 1,454 for Hospital Length of Stay B. n = 1,400 for ICU Length of Stay

Figure 4

Forest Plot of Antipsychotic Use and Mortality in Hospitalized Patients Abbreviations: SD = Standard Deviation; 95% CI – 95% Confidence Interval; df = degrees of freedom; MH = Mantel-Heanzel Odds Ratio; IV = Inverse Variance; Random = Random Effects Model used to calculate estimate; Fixed = Fixed Effects Model used to calculate the estimate. Total Number of Patients Combined for each Meta-analysis: Antispychotics vs. Placebo or No Treamtment: n = 1,262 Antipsychotics vs. Antipsychotics: n = 177 Total: n= 1,439