Melatonin and Ramelteon for the treatment of delirium: A systematic review and meta-analysis.

OBJECTIVE: To assess the efficacy of melatonin and melatonergic agonist for the treatment of delirium in hospitalized patients. METHODS: Embase, MEDLINE, PsycINFO, PubMed, CENTRAL, Cochrane Database of Systematic Reviews, TRIP Medical Database, ClinicalTrials.gov and Google were searched from inception to October 2022. Randomized controlled trials (RCT) and observational studies with any type of comparator evaluating melatonin or melatonergic agonist (ramelteon) enrolling any populations (ICU, surgery, geriatric) were included. Two reviewers independently selected and extracted data using the Cochrane risk of bias tools (RoB2 and ROBINSI). RESULTS: Out of the 650 screened publications, three RCTs and six observational studies were included (n = 1211). All three RCTs compared melatonin to placebo, as the majority of observational studies compared melatonin or ramelteon to antipsychotics. Two RCTs reported the duration of delirium and a meta-analysis provided a statistical difference between melatonin and placebo (-1.72 days, 95% CI -2.66 to -0.77, p = 0.0004). Five observational studies reported the duration of delirium but only one reported a statistical reduction in the duration of delirium. CONCLUSION: Although melatonin and ramelteon may be effective treatments for delirium, particularly to shorten the duration of delirium and to limit the use of rescue medication, current data is limited in number and in its quality. Clinicians should wait until higher quality data from ongoing RCTs are available before prescribing melatonin to delirious patients.

A randomized double-blind feasibility study comparing cetirizine and diphenhydramine in the prevention of paclitaxel-associated infusion-related reactions: the PREMED-F1 study.

PURPOSE: Cetirizine is a less sedative alternative to diphenhydramine for the prevention of infusion-related reactions (IRR) to paclitaxel. However, its use remains controversial. In this study, we assessed feasibility for a future definitive non-inferiority trial comparing cetirizine to diphenhydramine as premedication to prevent paclitaxel-related IRR. METHODS: This was a single-center randomized prospective feasibility study. Participants were paclitaxel-naive cancer patients scheduled to start paclitaxel chemotherapy. They were randomly assigned to receive either intravenous diphenhydramine 50 mg + oral placebo (control) or intravenous placebo + oral cetirizine 10 mg (intervention) for their first two paclitaxel treatments. The percentage of eligible patients completing a first paclitaxel treatment and the recruitment rate were assessed (feasibility outcomes). Drowsiness was measured at baseline and at selected time points using the Stanford Sleepiness Scale (SSS) (safety outcome). IRR events were also documented (efficacy outcome). RESULTS: Among 37 eligible patients, 27 were recruited and randomized (control 13; intervention 14) and 25 completed the study. The recruitment rate was 4.8 participants/month, meeting the primary feasibility target. Drowsiness was the main adverse effect associated with the premedication. The increase in drowsiness compared to baseline (ΔSSS) was greater in the diphenhydramine group compared to the cetirizine group (median ΔSSS 2 (IQR 3.25) vs median ΔSSS 0 (IQR 1), p < 0.01) when measured one hour after the premedication administration. One participant had an IRR and no unexpected serious adverse event occurred. CONCLUSION: The trial methods were feasible in terms of recruitment, retention, and safety. Cetirizine was significantly less sedating than diphenhydramine. IRR were infrequent and a larger trial is warranted to confirm non-inferiority for IRR prevention. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04237090 (22.01.2020).