Benzodiazepines for delirium
Open accessAbstract
BACKGROUND: Delirium occurs in 30% of hospitalised patients and is associated with prolonged hospital stay and increased morbidity and mortality. The results of uncontrolled studies have been unclear, with some suggesting that benzodiazepines may be useful in controlling non-alcohol related delirium. OBJECTIVES: To determine the effectiveness and incidence of adverse effects of benzodiazapines in the treatment of non-alcohol withdrawal related delirium. SEARCH STRATEGY: The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 26 February 2008 using the search terms: (deliri* or confusion) and (benzo* or lorazepam," or "alprazolam" or "ativan" or diazepam or valium or chlordiazepam).The CDCIG Specialized Register contains records from major health databases (including MEDLINE, EMBASE, CINAHL, PsycINFO, CENTRAL, LILACS) as well as many ongoing trial databases and grey literature sources. SELECTION CRITERIA: Trials had to be unconfounded, randomized and with concealed allocation of subjects. Additionally, selected trials had to have assessed patients pre- and post-treatment. Where crossover design was present, only data from the first part of the trial were to be examined. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data from included trials. Data were pooled where possible, and were to be analysed using appropriate statistical methods. Odd ratios or average differences were to be calculated. Only "intention to treat" data were to be included. MAIN RESULTS: Only one trial satisfying the selection criteria could be identified. In this trial, comparing the effect of the benzodiazepine, lorazepam, with dexmedetomidine, a selective alpha-2-adrenergic receptor agonist, on delirium among mechanically ventilated intensive care unit patients, dexmedetomidine treatment was associated with an increased number of delirium- and coma-free days compared with lorazepam treated patients (dexmedetomidine patients, average seven days; lorazepam patients, average three days; P = 0.01). One partially controlled study showed no advantage of a benzodiazepine (alprazolam) compared with neuroleptics in treating agitation associated with delirium, and another partially controlled study showed decreased effectiveness of a benzodiazepine (lorazepam), and increased adverse effects, compared with neuroleptics (haloperidol, chlorpromazine) for the treatment of acute confusion. AUTHORS' CONCLUSIONS: No adequately controlled trials could be found to support the use of benzodiazepines in the treatment of non-alcohol withdrawal related delirium among hospitalised patients, and at this time benzodiazepines cannot be recommended for the control of this condition. Because of the scarcity of trials with randomization of patients, placebo control, and adequate concealment of allocation of subjects, it is clear that further research is required to determine the role of benzodiazepines in the treatment of non-alcohol withdrawal related delirium.
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No evidence for medication efficacy, including cholinesterase inhibitors, antipsychotic medication, or melatonin, exists.
“However, no evidence for medication efficacy, including cholinesterase inhibitors, antipsychotic medication, or melatonin exists.287, 288, 289”
From Dementia prevention, intervention, and care: 2020 report of the Lancet Commission (2020) · cites this paper as [289]
The Characteristics of excluded studies section reports that haloperidol and chlorpromazine improved delirium in hospitalized AIDS patients, contrary to the claim that no evidence of antipsychotic medication efficacy exists. This review focuses on benzodiazepines; the cited passages do not assess cholinesterase inhibitors or melatonin. Page numbers were not available in our copy. (LLM, conf=0.85)
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- C H A R A C T E R I S T I C S O F S T U D I E S Characteristics of included studies [ordered by study ID] Methods Double-blind, randomized (computer-generated, permuted block randomization); intention to treat analysis Participants Medial and surgical ICU patients requiring mechanical ventilation for more than 24 hours. 106 patients 54 patients (average age, 59, 23 men) in control group. 52 patients (average age 60; 30 men) received study drug. Delirium diagnosed using IC-CAM method or RASS scale Interventions Patients were treated for up to 120 hrs, with: control group receiving intravenous lorazepam; study group receiving intravenous dexmedetomidine). Drug infusion rate was titrated to reach a sedation lev- el determined by the Richmond Agitation-Sedation Scale. Rescue intervention for acute agitation while on treatment included propofol infusion; for increased pain, fentanyl was given Outcomes Prevalence of coma was significantly higher among lorazepam patients compared with dexmedeto- midine patients (92% vs 63%; P < 0.001). Delirium-free days were not significantly different comparing the two groups (L pts av 7 d, D pts av 9 d, P = 0.09); delirium-free and coma free days were significantly greater for D patients compared with L patients (Dpts av 7 d, Lpts av 3 d; P = 0.01) Notes Authors note that dexmedetomidine has analgesic properties, but that this group received more fen- tanyl than lorazepam patients, introducing two uncontrolled variables (pain control and sedation ef- fect of fentanyl) that may have affected the outcomes. Authors (Prandharipande 2008) noted that the long half-life of lopazepam (8-15 hours) compared to dexmedetomidine (2 hours) could contibute to the differences in oversedation favoring the shorter acting drug. 2007 Benzodiazepines for delirium (Review) Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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- Authors
- Lonergan, E., Luxenberg, J., & Areosa Sastre, A.
- Affiliations
- 4 Captain Drive Apt 215 Emeryville CA USA 94608
- Jewish Home (US)
- c/ Mauricio Legendre 17, 5-A Madrid Spain 28046
- ORCID
- Luxenberg, Jay
- Venue
- Cochrane Database of Systematic Reviews
- Publisher
- Wiley
- Published
- 2009-10-07
- Volume
- 2010
- Issue
- 1
- Pages
- CD006379-CD006379
- ISSN
- 1361-6137 (ISSN-L)
- 1465-1858
- PMC
- PMC6669269
- OpenAlex
- W1903577601
- Cited by
- 223
- References
- 30
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 3 · 2023: 2 · 2022: 6 · 2021: 6 · 2020: 41 · 2019: 14 · 2018: 12 · 2017: 12 · 2016: 11 · 2015: 17 · 2014: 16 · 2013: 19 · 2012: 22
- FWCI
- 2.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cochrane Database of Systematic Reviews (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Intensive Care Unit Cognitive Disorders
- Health Sciences › Medicine › Neurology › Alcoholism and Thiamine Deficiency
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
- Keywords
- delirium, benzodiazepines, lorazepam, dexmedetomidine, alprazolam, antipsychotic drugs, haloperidol, chlorpromazine, agitation, mechanical ventilation, intensive care unit patients, adverse effects, treatment effectiveness, hospitalized patients, benzodiazepine withdrawal
- MeSH terms
- Benzodiazepines, Delirium, Humans, Lorazepam, Dexmedetomidine
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