Review: The effectiveness of pharmacologic interventions for treatment and prevention of delirium was assessed.
Wu YC, Tseng PT, Tu YK, et al. Association of Delirium Response and Safety of Pharmacological Interventions for the Management and Prevention of Delirium: A Network Meta-analysis. JAMA Psychiatry. 2019 Feb 27. pii: 2726609. doi: 10.1001/jamapsychiatry.2018.4365.

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.

Ratings
Specialty Area Score
Hospital Doctor/Hospitalists
Internal Medicine
Geriatrics
Intensivist/Critical Care
Oncology - Palliative and Supportive Care
Oncology - General
Comments from MORE raters

Geriatrics

The editorial by Dan Blazer questions the conclusion as well as the generalizability of the study. Before either should be used or touted, further studies need done to verify the benefits.

Internal Medicine

This is a meta-analysis with 2 studies 1 in treatment (haloperidol and lorazepam) and one of prevention (ramalteon) that made up the bulk of patients. Furthermore, criteria used for delirium was different in the studies making comparisons difficult.

Oncology - General

As an Oncologist, I find that, although this article focuses on an important subject, some trials with Palliative Care patients, quite frequent in Oncology were not included for analysis. Furthermore, there is information that is hard to explain, for instance, it is said that Midazolam is significantly associated with greater delirium but then it is the association of other drugs with benzodiazepines (including Midazolam) that gives the best treatment response rates. Delirium etiologies were diverse and that may contribute to some heterogeinity in the data. On the whole, I found the information useful but would be cautious to take these results as definitive proof of effect.

Oncology - Palliative and Supportive Care

The methodology can be criticized. Only one trial in a specific subgroup of patients supports the apparently best treatment for delirium.

The methodology can be criticized. Only one trial in a specific subgroup of patients supports the apparently best treatment for delirium.

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