Effects of Melatonin for Delirium in Elderly Acute Heart Failure Patients: A Randomized, Single-Center, Double-Blind, and Placebo-Controlled Trial

Abstract

Background: Delirium is a common, life-threatening, typical clinical syndrome with the main clinical manifestations of temporary organic mental disorder without specific drug treatment. The aim of the study was to explore the benefits of melatonin for the treatment of delirium after acute heart failure in elderly patients. Methods: This was a randomized, double-blind, and placebo-controlled trial. This study enrolled patients aged more than 60 years after acute heart failure. A computer-generated randomization sequence (in a 1:1 ratio) was used to randomly assign patients to receive either melatonin (3 mg/day, 7 days) or placebos. The primary endpoint was the incidence of delirium, assessed twice daily with the Confusion Assessment Method during the first 7 days. Analyses were performed by intention-to-treat and safety populations. Results: Between October 2015 and October 2019, 584 patients were assessed. A total of 497 patients randomly were assigned to receive either placebo (N = 249) or melatonin (N = 248). The incidence of delirium was significantly lower in the melatonin group than in the placebo group (27.0% vs. 36.9%, P = 0.021). Regarding safety, the occurrence of rhabdomyolysis and abnormal hepatic function did not differ between the two groups. Conclusion: The current study (clinical trial registered number: CHWX-904-201511) suggests that acute melatonin treatment can reduce the incidence of delirium for elderly acute heart failure. It also can reduce the time of hospital stays and hospitalization costs. The therapy was safe and worth spreading.

Prophylactic melatonin for delirium in critically ill patients: A systematic review and meta-analysis with trial sequential analysis

“…Six trials exclusively included surgical patients admitted to the ICU. Of these trials, 1 trial [16] included elderly patients with acute heart failure after surgery and did not explicitly report the type of surgery. In the remaining 5 trials, patients underwent liver resection, [24] elective on-pump coronary artery bypass graft surgery, [19,25] elective pulmonary thromboendarterectomy surgery, [20] and percutaneous transluminal coronary intervention surgery.…”

“…In our older patients aged ≥ 60 years, 5 trials with 956 patients provided data. Of these, 3 trials [16,18,25] included only older patients aged > 60 years, 1 trial [19] conducted by Jaiswal et al reported the incidence of delirium in patients aged ≥ 65 years, and the remaining 1 [19] by Zadeh et al reported the incidence of delirium in patients aged > 70 years. Melatonin reduced the occurrence of delirium in older patients (RR, 0.69; 95% CI: 0.57–0.83; I 2 = 0%).…”

“…Twelve trials, [7,11,[16][17][18][19][20][21][22][23][24][25] including 2538 patients, were evaluated and eligible for the meta-analysis. The flow diagram for study inclusion is shown in Figure 1.…”

“…The included trials were published between March 2011 [24] and April 2022, [7] with sample sizes ranging from 36 [24] to 841. [7] Ten trials [7,11,[16][17][18][19][22][23][24][25] used melatonin for delirium prevention and 2 trials [20,21] used ramelteon. The dosage and course of each trial are presented in Table 1.…”

“…Melatonin reduced the occurrence of delirium in older patients (RR, 0.69; 95% CI: 0.57-0.83; I 2 = 0%). In the cardiovascular disease subgroup, 5 trials, [16,[18][19][20]25] including 1081 patients, provided data. Melatonin did reduce the delirium occurrence in cardiovascular disease patients with diagnoses of cardiovascular diseases (RR, 0.70; 95% CI: 0.58-0.84; I 2 = 0%).…”