Table 1.
Studies of melatonin in acute medically ill and perioperative geriatric patients in delirium prevention
| Reference | Year | Study design | Intervention dosage/sample size | Comparator/sample size | Timing | Setting | Age (years) | Primary outcome | Assessment tool | Outcome |
|---|---|---|---|---|---|---|---|---|---|---|
| Jaiswal et al 15 | 2018 | RCT, blinded, ITT analysis | Melatonin 3 mg/n = 43 | Placebo/n = 44 | Nightly for 14 nights | Inpatients, internal medicine ward | 81.2 ± 7.3 (melatonin), 80.1 ± 8.3 | Delirium occurrence | CAM |
Melatonin 22.2% (8/36) vs placebo 9.1% (3/33) P = 0.19, NSS |
| Al‐Aama et al 16 | 2011 | Placebo‐controlled trial, double blind | Melatonin 0.5 mg/n = 61 | Placebo/n = 61 | Prior to sleep between 6 pm and midnight | Inpatients, emergency department to the internal medicine ward | 84.3 ± 5.9 (melatonin), 84.6 ± 6.2 (placebo) | Delirium incidence | CAM and MDAS |
Melatonin 12%, placebo 31% P = 0.01 |
| Artemiou et al 19 | 2015 | Prospective clinical observational study | Melatonin 5 mg/n = 250 | Placebo/n = 250 | Night before cardiac surgery | Inpatients, cardiac surgery | 65.2 ± 10.3 (melatonin), 64.3 ± 10.1 (control) | Incidence of postoperative delirium | CAM‐ICU |
Placebo 20.8% vs melatonin 8.4% P = 0.001 |
| Sultan et al 17 | 2010 | RCT, double blinded | Melatonin 5 mg/n = 53 | Placebo/n = 49, midazolam 7.5 mg/n = 50 or clonidine 100 µg/n = 51 | Night before operation | Inpatient, scheduled hip arthroplasty spinal anesthesia |
Control: 72.3 ± 6.4 Melatonin: 70.4 Midazolam: ±8.2 Clonidine: ±6.8 |
Delirium rate | AMT |
Placebo 32.65% vs melatonin 9.43% P = 0.003 Midazolam and clonidine groups, NSS |
| De Jonghe et al 14 | 2014 | RCT, multicenter, double blinded | Melatonin 3 mg/n = 186 | Placebo/n = 192 | Nightly around 9 pm for 5 days | Inpatients with emergency hip fracture | 84.1 ± 8 (melatonin), 83.4 ± 7.5 | Incidence of delirium | DSM‐5 | Melatonin 29.6% vs placebo 25.5% P = 0.4 |
| Chen et al 11 | 2016 |
Meta‐analysis Four RCTs included |
Melatonin 5 mg, 0.5 mg, 3 mg | Placebo/NA | Nightly, daily between 6 pm and midnight | Hospital admission to a medical ward | NA | Incidence of delirium | AMT, CAM, DSM‐5 |
Melatonin groups vs placebo RR 0.41; 95% CI, 0.15‐1.13, NSS |
| Ford et al 18 | 2020 | RCT, double blind, placebo‐controlled, ITT analysis | Melatonin 3 mg/n = 105 | Placebo/n = 105 | At night, started 2 days before surgery, continued 7 days | Inpatient, major cardiac surgery | 69 (melatonin group) and 67.6 (placebo), SD 8 | Incidence of delirium | CAM |
Melatonin 21.4% (21/98) vs placebo 20.2% (21/104) OR = 0.78; 95% CI, 0.35‐1.75, NSS |
Abbreviations: AMT, Abbreviated Mental Test; CAM, Confusion Assessment Model; CI, confidence interval; DSM‐5, Diagnostic and Statistical Manual of Mental Disorders, 5th edition; ICU, intensive care unit; ITT, intention‐to‐treat; MDAS, Memorial Delirium Assessment Scale; NSS, not statistically significant; OR, odds ratio; RCT, randomized controlled trial; RR, relative risk; SD, standard deviation.