Which medications provide the best delirium response rate, the lowest delirium occurrence rate, and the best tolerability for the treatment and prevention of delirium?
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.
The use of a combination of haloperidol plus lorazepam and ramelteon is suggested for the treatment and prevention of delirium.
Although several pharmacological interventions for delirium have been investigated, their overall benefit and safety remain unclear.
To evaluate evidence regarding pharmacological interventions for delirium treatment and prevention.
PubMed, Embase, ProQuest, ScienceDirect, Cochrane Central, Web of Science, ClinicalKey, and ClinicalTrials.gov from inception to May 17, 2018.
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.
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.
Wu Y, Tseng P, Tu Y, et al. Association of Delirium Response and Safety of Pharmacological Interventions for the Management and Prevention of Delirium: A Network Meta-analysis. JAMA Psychiatry. Published online February 27, 201976(5):526–535. doi:10.1001/jamapsychiatry.2018.4365
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