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JAMA Psychiatry. 2019 Feb 27. doi: 10.1001/jamapsychiatry.2018.4365. [Epub ahead of print]

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

Wu YC1, Tseng PT2, Tu YK3, Hsu CY4,5, Liang CS6,7, Yeh TC8, Chen TY8,9, Chu CS10,11, Matsuoka YJ12,13, Stubbs B14,15,16, Carvalho AF17,18, Wada S13, Lin PY19,20, Chen YW21, Su KP12,22,23.

Author information

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

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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