By: Dr. Geoffrey Modest<\/b><\/p>\n
There have been a few articles looking at melatonin and one of its derivatives to\u00a0decrease the development of delirium in hospitalized patients (thanks to my brother Andrew for bringing this to my attention). Delirium, from many studies, is common (30% of those hospitalized who are\u00a0over 65 yo, 40% in those in ICU, and is often underdiagnosed). One article looked at ramelteon, a melatonin agonist with high affinity for the MT1<\/sub> and MT2<\/sub> receptors (more potent than melatonin<\/span> by\u00a06-fold and 3-fold, respectively,\u00a0so that comparing 8mg of ramelteon has, for example, a\u00a016- and 8-fold increased potency vs 3mg of melatonin) —\u00a0see\u00a0JAMA Psychiatry. 2014;71(4):397-403<\/strong>). <\/span><\/span><\/p>\n Details of this study:<\/span><\/span><\/p>\n \u00a0<\/span>–67 patients (mean age 78, 40% male, with most\u00a0admitted with either\u00a0stroke, infection, or\u00a0fracture)\u00a0from 4 university hospitals and 1 general hospital in Japan.<\/span><\/p>\n –24 patients\u00a0in ICUs and 43 on hospital wards\u00a0were randomly assigned to\u00a0ramelteon 8mg\/d vs placebo nightly for 7 nights<\/span><\/p>\n Results:<\/span><\/p>\n –<\/span>-ramelteon was associated with\u00a0a lower risk of delirium (1 vs 11 patients:\u00a03% vs 32%, p=0.003) with RR 0.09 (0.01-0.69). the effect was evident within 2-3 days of admission<\/span><\/p>\n –controlling for risk factors (age, diagnosis of dementia, admission diagnosis of infection), ramelteon still significantly associated with decreased delirium risk [P=0.01, odds ratio 0.07 (0.008-0.54)]<\/span><\/p>\n –there were no differences in any of the sleep parameters in those on ramelteon (difficulty falling asleep, staying asleep, early awakening,\u00a0sleep quality or\u00a0duration), though more in the placebo group did get hydroxyzine, which has weak\u00a0anticholinergic effects, for sleep (though, controlling for\u00a0the\u00a0use of hydroxyzine, there\u00a0still was a\u00a0significant benefit of ramelteon on delirium). so, it does not seem that sleep deprivation had a significant role in the\u00a0occurrence\u00a0of delirium<\/span><\/p>\n –subgroup analysis showed ramelteon’s benefits were\u00a0even in those without prior history of delirium. (too few patients in sample with history of delirium to see any difference)<\/span><\/p>\n –adverse events potentially attributable to drug: zero \u00a0—\u00a0though other studies on ramelteon have shown slight increases in somnolence (5% vs 3%), dizziness (5% vs 3%) and fatigue (4% vs 2%)<\/span><\/p>\n This was a pretty benign intervention in a small number of patients but with pretty\u00a0dramatic outcome, especially since the only other medications showing any benefit in some studies are\u00a0antipsychotics that have\u00a0lots of adverse effects. Trials of\u00a0cholinesterase inhibitors (eg donepezil) mostly produce just adverse effects. other studies on ramelteon confirm its benefit in sleep-promotion in the elderly, at both the 4 and 8mg dosages (likely related to restoring the otherwise\u00a0decreasing endogenous melatonin levels with aging). Other small RCTs have found some benefit of melatonin at doses of 3mg, 5mg, and\u00a010mg in restoring circadian rhythms in ICU patients and decreasing delirium in\u00a0medical \u00a0or elective surgical patients. The main issues with this\u00a0ramelteon study is the small sample size, some differences in those with baseline dementia (24% in the placebo group and 15% in those on ramelteon), and lack of\u00a0breakdown of which patients were in the ICU vs the wards (though there was no difference in the APACHE scores, Charlson\u00a0comorbidity index, or performance status of the randomized\u00a0patients)<\/span><\/p>\n Bottom line:<\/span><\/p>\n –there seems to be some utility of melatonin or derivatives (ramelteon) in restoring circadian rhythm, sleep and preventing delirium in hospitalized patients<\/span><\/p>\n –the big issue to me with melatonin is that it is a “supplement”, not subject to the FDA regulation, and there have been\u00a0dramatic differences found in the actual amount of melatonin in the\u00a0advertised\u00a0doses.<\/span><\/p>\n –the average wholesale price of ramelteon (which is not\u00a0available as a generic) is\u00a0\u00a0$333 for 30 pills and requires a prior approval from medicaid …. \u00a0so, will stick with melatonin for now.<\/span><\/p>\n","protected":false},"excerpt":{"rendered":" By: Dr. Geoffrey Modest There have been a few articles looking at melatonin and one of its derivatives to\u00a0decrease the development of delirium in hospitalized patients (thanks to my brother Andrew for bringing this to my attention). Delirium, from many studies, is common (30% of those hospitalized who are\u00a0over 65 yo, 40% in those in […]<\/p>\n