Table 2 Characteristics and quantitative synthesis of the eligible MAs of MLT for health
From: Melatonin and health: an umbrella review of health outcomes and biological mechanisms of action
First author (year) [reference] | Health outcome | No of participants included in MA | No of primary studies included in MA | Reported effect size | Random-effects summary effect size (95% CI) | P random | Fixed-effects summary effect size (95% CI) | P fixed | 95% PI | I2 (%) | Estimate of the study with lowest SE in MA (95% CI)1 | Small-study effects/excess statistical significance |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
Addiction | ||||||||||||
 Wright2 (2015) [36] | Withdrawal symptoms | 244 | 4 | OR | 1.39 (0.42, 4.65) | 0.594 | 1.11 (0.65, 1.90) | 0.694 | 0.01, 277.67 | 75.9 | 1.00 (0.37, 2.67) | No/No |
Cancer | ||||||||||||
 Basler (2014) [68] | Risk of breast cancer | 1650 | 5 | RR | 0.82 (0.68, 0.99) | 0.043 | 0.82 (0.71, 0.95) | 0.01 | 0.50, 1.34 | 31.7 | 0.81 (0.64, 1.02) | No/No |
 Wang (2012) [31] | 761 | 8 | RR | 1.95 (1.49, 2.54) | 0.0001 | 1.96 (1.50, 2.56) | 0.0001 | 1.40, 2.71 | 0 | 2.25 (1.39, 3.64) | No/No | |
 Wang (2012) [31] | 590 | 5 | RR | 1.90 (1.28, 2.83) | 0.0002 | 1.82 (1.49, 2.24) | 0.0001 | 0.56, 6.47 | 61.9 | 1.26 (0.97, 1.65) | No/No | |
Delirium | ||||||||||||
 Chen (2015) [35] | Incidence of delirium | 669 | 4 | RR | 0.41 (0.15, 1.13) | 0.084 | 0.73 (0.55, 0.95) | 0.021 | 0.01, 35.8 | 83.8 | 1.16 (0.83, 1.61) | Yes/No |
Dementia | ||||||||||||
 Jansen3 (2009) [30] | Cognition | 121 | 2 | MD | –2.64 (–5.99, 0.71) | 0.123 | –2.12 (–3.82, 0.42) | 0.015 | – | 68.6 | –1.15 (–3.16, 0.86) | –/No |
 Jansen (2009) [30] | Mood and behaviour | 150 | 3 | MD | 0.18 (–0.73, 1.10) | 0.698 | 0.18 (–0.73, 1.10) | 0.698 | –5.76, –6.12 | 0 | –0.01 (–1.08, 1.06) | No/No |
Depression/mood disorders | ||||||||||||
 De Crescenzo (2017) [127] | Mood disorders | 181 | 3 | SMD | 0.37 (–0.05, 0.78) | 0.087 | 0.39 (0.08, 0.70) | 0.013 | –3.74, 4.47 | 43 | 0.32 (–0.14, 0.78) | No/No |
 Guaiana (2013) [34] | Response to treatment | 3826 | 10 | RR | 1.01 (0.95, 1.08) | 0.749 | 1.00 (0.95, 1.06) | 0.881 | 0.87. 1.17 | 31.4 | 1.04 (0.93, 1.15) | No/Yes |
 Huang (2014) [65] | 1871 | 6 | RR | 1.07 (1.02, 1.13) | 0.01 | 1.08 (1.03, 1.15) | 0.005 | 0.99, 1.16 | 0 | 1.04 (0.93, 1.15) | No/No | |
 Guaiana (2013) [34] | Remission | 3826 | 10 | RR | 0.83 (0.68, 1.02) | 0.069 | 0.87 (0.80, 0.94) | 0.0007 | 0.43, 1.59 | 77.8 | 0.95 (0.85, 1.06) | No/No |
 Huang (2014) [65] |  | 1742 | 5 | RR | 1.11 (1.01, 1.23) | 0.035 | 1.12 (1.01, 1.24) | 0.038 | 0.95, 1.31 | 0 | 1.09 (0.93, 1.27) | No/No |
 Hansen3 (2014) [65] | Hospital Anxiety and Depression Scale | 74 | 2 | MD | 0.97 (–0.84, 2.78) | 0.293 | 0.93 (–0.42, 2.28) | 0.178 | – | 44 | 0.10 (–1.72, 1.92) | –/No |
 Hansen3 (2014) [65] | Beck Depression Inventory | 91 | 2 | MD | –1.09 (–2.60, 0.42) | 0.157 | –1.09 (–2.60, 0.42) | 0.157 | – | 0 | –1.00 (–2.54, 0.54) | –/No |
Infertility | ||||||||||||
 Seko (2014) [25] | Pregnancy rate | 680 | 5 | RR | 1.21 (0.98, 1.49) | 0.071 | 1.21 (0.98, 1.50) | 0.071 | 0.86, –1.70 | 0 | 1.13 (0.85, 1.51) | No/No |
 Seko (2014) [25] | Oocytes retrieved | 680 | 5 | MD | 0.57 (–0.22, 1.35) | 0.155 | 0.23 (–0.12, 0.8) | 0.2 | –1.91, –3.04 | 68.7 | –0.07 (–0.57, 0.43) | Yes/No |
Pre- and post-operative care | ||||||||||||
 Andersen (2014) [33] | Pre-operative anxiety | 761 | 11 | SMD | –0.88 (–1.33, –0.44) | <0.0001 | –0.91 (–1.07, –0.75) | <0.0001 | –2.53, –0.76 | 86.7 | 0.00 (–0.33, 0.33) | No/No |
 Hansen3 (2015) [169] | 122 | 2 | MD | –1.18 (–2.59, 0.23) | 0.1 | –1.18 (–2.59, 0.23) | 0.1 | – | 0 | –1.30 (–2.76, 0.16) | –/No | |
 Hansen3 (2015) [169] | Post-operative anxiety | 73 | 2 | MD | –5.31 (–8.78, –1.84) | 0.003 | –5.31 (–8.78, –1.84) | 0.003 | – | 0 | –5.40 (–10.12, –0.68) | –/No |
 Andersen (2014) [33] | Post-operative pain | 524 | 8 | SMD | –1.06 (–1.89, –0.24) | 0.012 | –0.12 (–0.30, 0.07) | 0.205 | –3.97, 1.85 | 94.2 | 0.43 (0.09, 0.77) | Yes/No |
 Mihara (2015) [41] | Prevention of agitation | 170 | 3 | RR | 0.31 (0.16, 0.60) | <0.0001 | 0.29 (0.15, 0.56) | <0.0001 | 0.00, 23.06 | 0 | 0.40 (0.18, 0.89) | No/Yes |
Safety | ||||||||||||
 Liu (2012) [40] | Adverse effects | 2912 | 7 | RR | 1.10 (1.02, 1.20) | 0.009 | 1.11 (1.03, 1.20) | 0.006 | 1.02, 1.20 | 0 | 1.13 (0.97, 1.31) | No/Yes |
Primary sleep disorders | ||||||||||||
 Liu3 (2012) [40] | Sleep latency | 405 | 1 (with six subgroups) | MD | –14.26 (–18.54, –9.98) | <0.0001 | –14.26 (–18.54, –9.98) | <0.0001 | –20.32, –8.19 | 0 | –16.70 (–26.82, –6.58) | –/NE |
 Kuriyama (2014) [39] | 5781 | 12 | WMD | –4.15 (–6.82, –1.47) | 0.002 | –3.30 (–4.88, –1.71) | <0.0001 | –11.69, 3.39 | 52.2 | –2.40 (–5.28, 0.48) | No/No | |
 Liira (2014) [38] | 148 | 5 | MD | –0.15 (–2.48, 2.18) | 0.899 | –0.41 (–2.32, 1.50) | 0.674 | –5.64, 5.34 | 21.6 | –1.10 (–3.83, 1.63) | Yes/No | |
 Liira (2014) [38] | 266 | 7 | MD | 24.30 (9.80, 38.80) | 0.001 | 24.30 (9.80, 38.80) | 0.001 | 5.29, 43.32 | 0 | 23.00 (–3.13, 49.13) | No/No | |
 Kuriyama (2014) [39] | Sleep quality | 5812 | 13 | SMD | –0.08 (–0.13, –0.03) | 0.003 | –0.08 (–0.13, –0.03) | 0.003 | –0.14, –0.02 | 0 | –0.15 (–0.27, –0.02) | No/No |
 Zhang3 (2016) [157] | 18 | 1 | MD | 4.20 (0.92, 7.48) | 0.012 | 4.20 (0.92, 7.48) | 0.012 | – | – | 4.20 (0.92, 7.48) | –/No | |
Animal studies | ||||||||||||
 Yang (2016) [32] | Spinal cord injury | 90 | 6 | MD | 1.52 (0.06, 2.98) | 0.041 | 1.29 (0.82, 1.77) | <0.0001 | –3.69, 6.73 | 89 | 0.16 (–0.88, 1.20) | Yes/No |