. 2019 May 1;76(5):526-535.

doi: 10.1001/jamapsychiatry.2018.4365.

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

Yi-Cheng Wu¹, Ping-Tao Tseng², Yu-Kang Tu³, Chung-Yao Hsu^{4

5}, Chih-Sung Liang^{6

7}, Ta-Chuan Yeh⁸, Tien-Yu Chen^{8

9}, Che-Sheng Chu^{10

11}, Yutaka J Matsuoka^{12

13}, Brendon Stubbs^{14

15

16}, Andre F Carvalho^{17

18}, Saho Wada¹³, Pao-Yen Lin^{19

20}, Yen-Wen Chen²¹, Kuan-Pin Su^{12

22

23}

Affiliations

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.

PMID: 30810723
PMCID: PMC6495351
DOI: 10.1001/jamapsychiatry.2018.4365

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

Yi-Cheng Wu et al. JAMA Psychiatry. 2019.

. 2019 May 1;76(5):526-535.

doi: 10.1001/jamapsychiatry.2018.4365.

Authors

Affiliations

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.

PMID: 30810723
PMCID: PMC6495351
DOI: 10.1001/jamapsychiatry.2018.4365

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.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Figures

See this image and copyright information in PMC

Comment in

Pharmacologic Intervention for the Treatment and Prevention of Delirium: Looking Beneath the Modeling.
Blazer DG. Blazer DG. JAMA Psychiatry. 2019 May 1;76(5):472-473. doi: 10.1001/jamapsychiatry.2018.4276. JAMA Psychiatry. 2019. PMID: 30810716 No abstract available.
Pharmacological Management of Delirium.
Neerland BE, Neufeld KJ, Slooter AJC. Neerland BE, et al. JAMA Psychiatry. 2019 Sep 1;76(9):983. doi: 10.1001/jamapsychiatry.2019.1513. JAMA Psychiatry. 2019. PMID: 31268505 No abstract available.
Pharmacological Management of Delirium-Reply.
Tseng PT, Su KP. Tseng PT, et al. JAMA Psychiatry. 2019 Sep 1;76(9):983-984. doi: 10.1001/jamapsychiatry.2019.1522. JAMA Psychiatry. 2019. PMID: 31268510 No abstract available.

References

1. Inouye SK, Westendorp RG, Saczynski JS. Delirium in elderly people. Lancet. 2014;383(9920):911-922. doi:10.1016/S0140-6736(13)60688-1 - DOI - PMC - PubMed
1. Siddiqi N, House AO, Holmes JD. Occurrence and outcome of delirium in medical in-patients: a systematic literature review. Age Ageing. 2006;35(4):350-364. doi:10.1093/ageing/afl005 - DOI - PubMed
1. Demeure MJ, Fain MJ. The elderly surgical patient and postoperative delirium. J Am Coll Surg. 2006;203(5):752-757. doi:10.1016/j.jamcollsurg.2006.07.032 - DOI - PubMed
1. Fero KE, Coe TM, Fanta PT, Tang CM, Murphy JD, Sicklick JK. Surgical management of adolescents and young adults with gastrointestinal stromal tumors: a US population-based analysis. JAMA Surg. 2017;152(5):443-451. doi:10.1001/jamasurg.2016.5047 - DOI - PMC - PubMed
1. Inouye SK, Bogardus ST Jr, Charpentier PA, et al. . A multicomponent intervention to prevent delirium in hospitalized older patients. N Engl J Med. 1999;340(9):669-676. doi:10.1056/NEJM199903043400901 - DOI - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions
Actions

Grants and funding

ICA-CL-2017-03-001/DH_/Department of Health/United Kingdom

LinkOut - more resources

Full Text Sources
Other Literature Sources
- H1 Connect - Access expert opinions and insights on biomedical research.
Medical
- ClinicalTrials.gov
- MedlinePlus Health Information

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Comment in

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical