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Original Investigation
February 27, 2019

Association of Delirium Response and Safety of Pharmacological Interventions for the Management and Prevention of Delirium: A Network Meta-analysis

Author Affiliations
  • 1Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
  • 2WinShine Clinics in Specialty of Psychiatry, Kaohsiung City, Taiwan
  • 3Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei
  • 4Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
  • 5Department of Neurology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
  • 6Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan
  • 7Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
  • 8Department of Psychiatry, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan
  • 9Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan
  • 10Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
  • 11Center for Geriatrics and Gerontology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
  • 12Institute of Neural and Cognitive Sciences, China Medical University Hospital, Taichung, Taiwan
  • 13Division of Health Care Research, Center for Public Health Sciences, National Cancer Center Japan, Tokyo
  • 14Physiotherapy Department, South London and Maudsley National Health Service Foundation Trust, London, United Kingdom
  • 15Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, De Crespigny Park, London, United Kingdom
  • 16Faculty of Health, Social Care and Education, Anglia Ruskin University, Chelmsford, United Kingdom
  • 17Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
  • 18Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada
  • 19Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
  • 20Institute for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
  • 21Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung, Taiwan
  • 22Department of Psychiatry & Mind-Body Interface Laboratory (MBI-Lab), China Medical University Hospital, Taichung, Taiwan
  • 23College of Medicine, China Medical University, Taichung, Taiwan
JAMA Psychiatry. 2019;76(5):526-535. doi:10.1001/jamapsychiatry.2018.4365
Key Points

Question  Which medications provide the best delirium response rate, the lowest delirium occurrence rate, and the best tolerability for the treatment and prevention of delirium?

Findings  From the results of a network meta-analysis of 58 randomized clinical trials among 9603 individuals, haloperidol plus lorazepam had the best response rate for delirium treatment, and ramelteon had the lowest delirium occurrence rate. No pharmacological management was significantly associated with a higher risk of all-cause mortality compared with placebo or control groups during delirium treatment or prevention.

Meaning  The use of a combination of haloperidol plus lorazepam and ramelteon is suggested for the treatment and prevention of delirium.

Abstract

Importance  Although several pharmacological interventions for delirium have been investigated, their overall benefit and safety remain unclear.

Objective  To evaluate evidence regarding pharmacological interventions for delirium treatment and prevention.

Data Sources  PubMed, Embase, ProQuest, ScienceDirect, Cochrane Central, Web of Science, ClinicalKey, and ClinicalTrials.gov from inception to May 17, 2018.

Study Selection  Randomized clinical trials (RCTs) examining pharmacological interventions for delirium treatment and prevention.

Data Extraction and Synthesis  To extract data according to a predetermined list of interests, the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines were applied, and all meta-analytic procedures were conducted using a random-effects model.

Main Outcomes and Measures  The primary outcomes were treatment response in patients with delirium and the incidence of delirium in patients at risk of delirium.

Results  A total of 58 RCTs were included, in which 20 RCTs with 1435 participants (mean age, 63.5 years; 65.1% male) compared the outcomes of treatment and 38 RCTs with 8168 participants (mean age, 70.2 years; 53.4% male) examined the prevention of delirium. A network meta-analysis demonstrated that haloperidol plus lorazepam provided the best response rate for delirium treatment (odds ratio [OR], 28.13; 95% CI, 2.38-333.08) compared with placebo/control. For delirium prevention, the ramelteon, olanzapine, risperidone, and dexmedetomidine hydrochloride groups had significantly lower delirium occurrence rates than placebo/control (OR, 0.07; 95% CI, 0.01-0.66 for ramelteon; OR, 0.25; 95% CI, 0.09-0.69 for olanzapine; OR, 0.27; 95% CI, 0.07-0.99 for risperidone; and OR, 0.50; 95% CI, 0.31-0.80 for dexmedetomidine hydrochloride). None of the pharmacological treatments were significantly associated with a higher risk of all-cause mortality compared with placebo/control.

Conclusions and Relevance  This network meta-analysis demonstrated that haloperidol plus lorazepam might be the best treatment and ramelteon the best preventive medicine for delirium. None of the pharmacological interventions for treatment or prophylaxis increased the all-cause mortality.

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