Published in the journal Lancet Respiratory Medicine. Here is a link to the article.
Regenstrief Institute authors: Babar Khan M.D.
The MIND-USA study explored the long-term effects of antipsychotic medications—haloperidol and ziprasidone—on critically ill patients experiencing delirium. This follow-up analysis was conducted at 16 U.S. hospitals, focusing on adult ICU patients with respiratory failure or shock who developed delirium. Participants were randomly assigned to receive haloperidol, ziprasidone or a placebo intravenously for up to 14 days. Outcomes were assessed at three and 12 months post-randomization, examining cognitive, functional, psychological, quality-of-life and employment metrics using standardized telephone assessments.
Of the nearly 21,000 individuals screened, more than 560 met eligibility criteria and were enrolled. At follow-up, all three groups showed similar survival and response rates. Cognitive impairment remained common across all groups, with approximately one-third of patients affected at both three and 12 months. Over half the survivors in each group were unable to return to work due to cognitive or physical limitations. Importantly, statistical analysis revealed no significant differences between the placebo and antipsychotic-treated groups in any measured long-term outcomes. Adjusted odds ratios showed minimal effect of either haloperidol or ziprasidone on cognitive scores or other quality-of-life indicators.
The study concludes that haloperidol and ziprasidone do not improve long-term cognitive, functional or psychological outcomes in delirious ICU patients. Given the lack of both short- and long-term benefit and concerns over continued antipsychotic use after discharge, the findings support avoiding routine antipsychotic administration for delirium in critically ill adults. These results have important implications for clinical guidelines and prescribing practices in intensive care settings.
Authors
Matthew F. Mart1, Leanne M. Boehm2, Amy L. Kiehl3, Michelle N. Gong4, Atul Malhotra5, Robert L. Owens5, Babar A. Khan6, Margaret A. Pisani7, Gregory A. Schmidt8, R. Duncan Hite9, Matthew C. Exline10, Shannon S. Carson11, Catherine L. Hough12, Peter Rock13, Ivor S. Douglas14, Daniel J. Feinstein15, Robert C. Hyzy16, William D. Schweickert17, David L. Bowton18, Andrew Masica19, Onur M. Orun20, Rameela Raman20, Brenda T. Pun3, Cayce Strength3, Mark L. Rolfsen21, Pratik P. Pandharipande22, Nathan E. Brummel23, Christopher G. Hughes22, Mayur B. Patel24, Joanna L. Stollings25, E. Wesley Ely1, James C. Jackson1, Timothy D. Girard26
Author Affiliations
1Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center, Nashville, TN, USA; Veterans Affairs Tennessee Valley Health System Geriatric Research, Education, and Clinical Center (GRECC), Nashville, TN, USA.
2Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center, Nashville, TN, USA; Veterans Affairs Tennessee Valley Health System Geriatric Research, Education, and Clinical Center (GRECC), Nashville, TN, USA; Vanderbilt University School of Nursing, Nashville, TN, USA.
3Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center, Nashville, TN, USA.
4Division of Critical Care Medicine, Division of Pulmonary Medicine, Department of Medicine, Montefiore Healthcare System/Albert Einstein College of Medicine, New York, NY, USA.
5Division of Pulmonary, Critical Care and Sleep Medicine, University of California San Diego, La Jolla, CA, USA.
6Division of Pulmonary, Critical Care, Sleep and Occupational Medicine, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
7Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT, USA.
8Division of Pulmonary, Critical Care and Occupational Medicine, University of Iowa, Iowa City, IA, USA.
9Division of Pulmonary Disease and Critical Care Medicine, Department of Medicine, University of Cincinnati, Cincinnati, OH, USA.
10Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University College of Medicine, Columbus, OH, USA.
11Division of Pulmonary Diseases and Critical Care Medicine, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
12Division of Pulmonary and Critical Care Medicine, Department of Medicine, Oregon Health and Science University School of Medicine, Portland, OR, USA.
13Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD, USA.
14Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
15Novant Healthcare, Winston-Salem, NC, USA.
16Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
17Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
18Department of Anesthesiology, Section on Critical Care, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
19Texas Health Resources, Arlington, TX, USA.
20Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA; Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center, Nashville, TN, USA.
21Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center, Nashville, TN, USA.
22Division of Anesthesiology Critical Care Medicine, Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN, USA; Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center, Nashville, TN, USA.
23Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center, Nashville, TN, USA; Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University College of Medicine, Columbus, OH, USA.
24Section of Surgical Sciences, Division of Acute Care Surgery, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA; Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center, Nashville, TN, USA.
25Department of Pharmaceutical Services, Vanderbilt University Medical Center, Nashville, TN, USA; Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center, Nashville, TN, USA.
26Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center, Nashville, TN, USA; Center for Research, Investigation, and Systems Modeling of Acute Illness (CRISMA), Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: timothy.girard@pitt.edu.
