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Meta-Analysis
. 2006 Jan 25;2006(1):CD003802.
doi: 10.1002/14651858.CD003802.pub3.

Melatonin for cognitive impairment

S L Jansen, D A Forbes, V Duncan, D G Morgan
Meta-Analysis

Melatonin for cognitive impairment

S L Jansen et al. Cochrane Database Syst Rev. .

Abstract

Background: There are a number of studies that suggest a relationship between decline of melatonin function and the symptoms of dementia.

Objectives: The review assessed the evidence of clinical efficacy and safety of melatonin in the treatment of manifestations of dementia or cognitive impairment (CI).

Search strategy: The Cochrane Dementia and Cognitive Improvement Group's Specialized Register was searched for trials involving melatonin on 5 October 2005. The search terms used were MELATONIN, and N-ACETYL-5-METHOXYTRYPTAMINE. This Register contains records from all major health care databases as well as many ongoing trials databases and is updated regularly.

Selection criteria: All relevant, randomized controlled trials in which orally administered melatonin in any dosage was compared with a control group for the effect on managing cognitive, behavioural (excluding sleep), and/or affective disturbances of people with dementia of any degree of severity.

Data collection and analysis: Two to three reviewers independently assessed the retrieved articles for relevance and methodological quality, and extracted data from the selected studies. Statistically significant differences in changes in outcomes from baseline to end of treatment between the melatonin and control groups were examined. Each study was summarized using a measure of effect (e.g. mean difference) and meta-analyses were conducted when appropriate.

Main results: Three studies met the inclusion criteria. This review revealed non-significant effects from the pooled estimates of MMSE cognitive, and ADAS-cognitive change scores. Individual study estimates for treatment effect demonstrated a significant improvement for melatonin compared with placebo in behavioural and affective symptoms as measured by the ADAS non-cognitive scale in a study of 20 patients, and the Neuropsychiatric Inventory (NPI) following treatment with 2.5 mg/day (SR) melatonin, but not with 10mg/day (IR) melatonin in a larger study of 157 patients. The remainder of the treatment effects for affect, behaviour and activities of daily living were non-significant.

Authors' conclusions: There is insufficient evidence to support the effectiveness of melatonin in managing the cognitive and non-cognitive sequelae of dementia.

PubMed Disclaimer

Conflict of interest statement

None known

Figures

1
1
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
2
2
Risk of Bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Forest plot of comparison: 1 Cognition: Melatonin vs Placebo, outcome: 1.1 MMSE Cognition Score at endpoint from baseline (change scores at 4 weeks, 3 mg MLT; 7 weeks, 2.5 mg MLT) and at final endpoint measure (6 weeks, 2.5 mg MLT).
4
4
Forest plot of comparison: 1 Cognition: Melatonin vs Placebo, outcome: 1.2 MMSE Cognition Score at endpoint from baseline (7 weeks, 10 mg MLT).
5
5
Forest plot of comparison: 1 Cognition: Melatonin vs Placebo, outcome: 1.3 MMSE Cognition Score at final endpoint measure (1 year, 2.5 mg MLT).
6
6
Forest plot of comparison: 1 Cognition: Melatonin vs Placebo, outcome: 1.4 MMSE Cognition Score at final endpoint measure (2 years, 2.5 mg MLT).
7
7
Forest plot of comparison: 1 Cognition: Melatonin vs Placebo, outcome: 1.5 ADAS Cognitive score at endpoint from baseline (4 weeks, 3 mg MLT; 7 weeks, 2.5 mg MLT).
8
8
Forest plot of comparison: 1 Cognition: Melatonin vs Placebo, outcome: 1.6 ADAS Cognitive Score at endpoint from baseline (7 weeks, 10.0 mg MLT).
9
9
Forest plot of comparison: 2 Behavior and Mood: Melatonin vs Placebo, outcome: 2.1 Mood and Behavioral Score at endpoint from baseline (NPI, 7 weeks, 2.5 mg; ADAS non‐cognitive, 4 weeks, 3 mg MLT)
10
10
Forest plot of comparison: 2 Behavior and Mood: Melatonin vs Placebo, outcome: 2.2 Mood and Behavioral score at endpoint from baseline (NPI, 7 weeks, 10 mg MLT).
11
11
Forest plot of comparison: 2 Behavior and Mood: Melatonin vs Placebo, outcome: 2.3 NPI‐Q Severity Score at final endpoint measure (6 weeks, 2.5 mg MLT)
12
12
Forest plot of comparison: 2 Behavior and Mood: Melatonin vs Placebo, outcome: 2.4 NPI‐Q Severity Score at final endpoint measure (1 year, 2.5 mg MLT).
13
13
Forest plot of comparison: 2 Behavior and Mood: Melatonin vs Placebo, outcome: 2.5 NPI‐Q severity Score at final endpoint measure (2 years, 2.5 mg MLT).
14
14
Forest plot of comparison: 2 Behavior and/or Mood: Melatonin vs Placebo, outcome: 2.6 Cohen‐Mansfield Agitation Inventory Score at final endpoint measure (6 weeks, 2.5 mg MLT).
15
15
Forest plot of comparison: 2 Behavior and Mood: Melatonin vs Placebo, outcome: 2.7 Cohen‐Mansfield Agitation Inventory Score at final endpoint measure (1 year, 2.5 mg MLT).
16
16
Forest plot of comparison: 2 Behavior and Mood: Melatonin vs Placebo, outcome: 2.8 Cohen‐Mansfield Agitation Inventory Score at final endpoint measure (2 years, 2.5 mg MLT).
17
17
Forest plot of comparison: 2 Behavior and Mood: Melatonin vs Placebo, outcome: 2.9 Mood and behavior score in Multi Observation Scale for Elderly Subjects at final endpoint measure (6 weeks, 2.5 mg MLT).
18
18
Forest plot of comparison: 2 Behavior and Mood: Melatonin vs Placebo, outcome: 2.10 Mood and behavior score in Multi Observation Scale for Elderly Subjects at final endpoint measure (1 year, 2.5 mg MLT).
19
19
Forest plot of comparison: 2 Behavior and Mood: Melatonin vs Placebo, outcome: 2.11 Mood and behavior score in Multi Observation Scale for Elderly Subjects at final endpoint measure (2 years, 2.5 mg MLT).
20
20
Forest plot of comparison: 2 Behavior and Mood: Melatonin vs Placebo, outcome: 2.12 Cornell Depression Rating Scale Score for Dementia at final endpoint measure (6 weeks, 2.5 mg MLT).
21
21
Forest plot of comparison: 2 Behavior and Mood: Melatonin vs Placebo, outcome: 2.13 Cornell Depression Rating Scale Score for Dementia at final endpoint measure (1 year, 2.5 mg MLT).
22
22
Forest plot of comparison: 2 Behavior and Mood: Melatonin vs Placebo, outcome: 2.14 Cornell Depression Rating Scale Score for Dementia at final endpoint measure (2 years, 2.5 mg MLT).
23
23
Forest plot of comparison: 2 Behavior and Mood: Melatonin vs Placebo, outcome: 2.16 Mood score in Philadelphia Geriatric Centre Affect Rating Scale (positive) at final endpoint measure (1 year, 2.5 mg MLT).
24
24
Forest plot of comparison: 2 Behavior and Mood: Melatonin vs Placebo, outcome: 2.15 Mood Score in Philadelphia Geriatric Centre Rating Scale (positive) at final endpoint measure (6 weeks, 2.5 mg MLT).
25
25
Forest plot of comparison: 2 Behavior and Mood: Melatonin vs Placebo, outcome: 2.17 Mood score in Philadelphia Geriatric Centre Affect Rating Scale (positive) at final endpoint measure (2 years, 2.5 mg MLT).
26
26
Forest plot of comparison: 2 Behavior and Mood: Melatonin vs Placebo, outcome: 2.18 Mood score in Philadelphia Geriatric Centre Affect Rating Scale (negative) at final endpoint measure (6 weeks, 2.5 mg MLT).
27
27
Forest plot of comparison: 2 Behavior and Mood: Melatonin vs Placebo, outcome: 2.19 Mood score in Philadelphia Geriatric Centre Affect Rating Scale (negative) at final endpoint measure (1 year, 2.5 mg MLT).
28
28
Forest plot of comparison: 2 Behavior and Mood: Melatonin vs Placebo, outcome: 2.20 Mood score in Philadelphia Geriatric Centre Affect Rating Scale (negative) at final endpoint measure (2 years, 2.5 mg MLT).
29
29
Forest plot of comparison: 2 Behavior and Mood: Melatonin vs Placebo, outcome: 2.21 Mood score in Philadelphia Geriatric Centre Morale Scale at final endpoint measure (6 weeks, 2.5 mg MLT).
30
30
Forest plot of comparison: 2 Behavior and Mood: Melatonin vs Placebo, outcome: 2.22 Mood score in Philadelphia Geriatric Centre Morale Scale at final endpoint measure (1 year, 2.5 mg MLT).
31
31
Forest plot of comparison: 2 Behavior and Mood: Melatonin vs Placebo, outcome: 2.23 Mood score in Philadelphia Geriatric Centre Morale Scale at final endpoint measure (2 years, 2.5 mg MLT).
32
32
Forest plot of comparison: 3 Functions of Daily Living: Melatonin vs Placebo, outcome: 3.1 ADL score at final endpoint measure (NI‐ADL, 6 weeks, 2.5 mg MLT).
33
33
Forest plot of comparison: 3 Functions of Daily Living: Melatonin vs Placebo, outcome: 3.2 NI‐ADL Score at final endpoint measure (1 year, 2.5 mg).
34
34
Forest plot of comparison: Functions of Daily Living: Melatonin vs Placebo, outcome: 3.3 NI‐ADL Score at final endpoint measure (ADL, 2 years, 2.5 mg MLT).
35
35
Forest plot of comparison: 4 Sensitivity Analysis: MMSE Cognition Score, outcome: 4.1 MMSE Cognition Score at endpoint from baseline (change scores at 4 weeks, 3 mg MLT; 7 weeks, 2.5 mg MLT).
36
36
Forest plot of comparison: 6 Adverse Events, outcome: 5.3 Mean AE Seriousness (Melatonin 2.5 mg at 7 weeks).
37
37
Forest plot of comparison: 6 Adverse Events (AE), outcome: 5.7 Mean AE Seriousness (Melatonin 10 mg at 7 weeks).
38
38
Forest plot of comparison: 6 Adverse Events: outcome 5.1 Mean Number of AE Reports per Person (Melatonin 2.5 mg at 7 weeks).
39
39
Forest plot of comparison: 6 Adverse Events, outcome: 5.5 Mean Number of AE Reports per Person (Melatonin 10 mg at 7 weeks).
40
40
Forest plot of comparison: 6 Adverse Events, outcome: 5.2 Mean AE Severity (Melatonin 2.5 mg at 7 weeks).
41
41
Forest plot of comparison: 6 Adverse Events, outcome: 5.6 Mean AE Severity (Melatonin 10 mg at 7 weeks).
42
42
Forest plot of comparison: 6 Adverse Events, outcome: 5.4 Mean AE Relatedness to Melatonin (Melatonin 2.5 mg at 7 weeks).
43
43
Forest plot of comparison: 6 Adverse Events (AE), outcome: 5.8 Mean AE Relatedness (Melatonin 10 mg at 7 weeks).
44
44
Forest plot of comparison: 7 Adverse Effects: Melatonin vs Placebo, outcome: 6.1 Mean Adverse Effect Ratings for Dizziness (Melatonin 2.5 mg over 3.5 years follow‐up).
45
45
Forest plot of comparison: 7 Adverse Effects, outcome: 6.2 Mean Adverse Effect Ratings for Drowsiness (Melatonin 2.5 mg over 3.5 yeas follow‐up).
46
46
Forest plot of comparison: 7 Adverse Effects: Melatonin vs Placebo, outcome: 6.3 Mean Adverse Effect Ratings for Eye Complaints (Melatonin 2.5 mg over 3.5 years follow‐up).
47
47
Forest plot of comparison: 7 Adverse Effects: Melatonin vs Placebo, outcome: 6.4 Mean Adverse Effect Ratings for Feebleness (Melatonin 2.5 mg over 3.5 years follow‐up).
48
48
Forest plot of comparison: 7 Adverse Effects: Melatonin vs Placebo, outcome: 6.5 Mean Adverse Effect Ratings for Headache (Melatonin 2.5 mg over 3.5 years follow‐up).
49
49
Forest plot of comparison: 7 Adverse Effects: Melatonin vs Placebo, outcome: 6.6 Mean Adverse Effect Ratings for Hunger (Melatonin 2.5 mg over 3.5 years follow‐up).
50
50
Forest plot of comparison: 7 Adverse Effects: Melatonin vs Placebo, outcome: 6.7 Mean Adverse Effects Ratings for Hyperactivity (Melatonin 2.5 mg over 3.5 years follow‐up).
51
51
Forest plot of comparison: 7 Adverse Effects: Melatonin vs Placebo, outcome: 6.8 Mean Adverse Effect Ratings for Inability to Sleep (Melatonin 2.5 mg over 3.5 years follow‐up).
52
52
Forest plot of comparison: 7 Adverse Effects: Melatonin vs Placebo, outcome: 6.9 Mean Adverse Effect Ratings for Irritability (Melatonin 2.5 mg over 3.5 years follow‐up).
53
53
Forest plot of comparison: 7 Adverse Effects: Melatonin vs Placebo, outcome: 6.10 Mean Adverse Effect Ratings for Nausea (Melatonin 2.5 mg over 3.5 years follow‐up).
54
54
Forest plot of comparison: 7 Adverse Effects: Melatonin vs Placebo, outcome: 6.11 Mean Adverse Effect Ratings for Constipation (Melatonin 2.5 mg over 3.5 years follow‐up).
55
55
Forest plot of comparison: 7 Adverse Effects: Melatonin vs Placebo, outcome: 6.12 Mean Adverse Effect Ratings for Pins and Needles (Melatonin 2.5 mg over 3.5 years follow‐up).
56
56
Forest plot of comparison: 7 Adverse Effects: Melatonin vs Placebo, outcome: 6.13 Mean Adverse Effect Ratings for Stomach Ache (Melatonin 2.5 mg over 3.5 years follow‐up).
57
57
Forest plot of comparison: 7 Adverse Effects: Melatonin vs Placebo, outcome: 6.14 Mean Adverse Effect Ratings for Sweating (Melatonin 2.5 mg over 3.5 years follow‐up).
58
58
Forest plot of comparison: 7 Adverse Effects: Melatonin vs Placebo, outcome: 6.15 Mean Adverse Effect Ratings for Trembling Hands (Melatonin 2.5 mg over 3.5 years follow‐up).
59
59
Forest plot of comparison: 7 Adverse Effects: Melatonin vs Placebo, outcome: 6.16 Mean Adverse Effect Ratings for Other Complications (Melatonin 2.5 mg over 3.5 years follow‐up).
1.1
1.1. Analysis
Comparison 1 Cognition: Melatonin vs Placebo, Outcome 1 MMSE Cognition Scores at endpoint from baseline (change scores at 4 weeks, 3 mg MLT; 7 weeks, 2.5 mg MLT) and at final endpoint measure (6 weeks, 2.5 mg MLT).
1.2
1.2. Analysis
Comparison 1 Cognition: Melatonin vs Placebo, Outcome 2 MMSE Cognition Scores at endpoint from baseline (7 weeks, 10 mg MLT).
1.3
1.3. Analysis
Comparison 1 Cognition: Melatonin vs Placebo, Outcome 3 MMSE Cognition Score at final endpoint measure (1 year, 2.5 mg MLT).
1.4
1.4. Analysis
Comparison 1 Cognition: Melatonin vs Placebo, Outcome 4 MMSE Cognition Score at final endpoint measure (2 years, 2.5 mg MLT).
1.5
1.5. Analysis
Comparison 1 Cognition: Melatonin vs Placebo, Outcome 5 ADAS Cognitive Score at final endpoint measure (4 weeks, 3 mg MLT; 7 weeks, 2.5 mg MLT).
1.6
1.6. Analysis
Comparison 1 Cognition: Melatonin vs Placebo, Outcome 6 ADAS Cognitive Score at final endpoint meaure (7 weeks, 10 mg MLT).
2.1
2.1. Analysis
Comparison 2 Behavior and/or Mood: Melatonin vs Placebo, Outcome 1 Behavioral and Mood Score at endpoint from baseline (NPI, 7 weeks, 2.5 mg MLT; ADAS non‐cognitive, 4 weeks, 3 mg MLT).
2.2
2.2. Analysis
Comparison 2 Behavior and/or Mood: Melatonin vs Placebo, Outcome 2 Behavioral and Mood Score at endpoint from baseline (NPI, 7 weeks, 10 mg MLT).
2.3
2.3. Analysis
Comparison 2 Behavior and/or Mood: Melatonin vs Placebo, Outcome 3 NPI‐Q Severity Score at final endpoint measure (6 weeks, 2.5 mg MLT).
2.4
2.4. Analysis
Comparison 2 Behavior and/or Mood: Melatonin vs Placebo, Outcome 4 NPI‐Q Severity Score at final endpoint measure (1 year, 2.5 mg MLT).
2.5
2.5. Analysis
Comparison 2 Behavior and/or Mood: Melatonin vs Placebo, Outcome 5 NPI‐Q severity Score at final endpoint measure (2 years, 2.5 mg MLT).
2.6
2.6. Analysis
Comparison 2 Behavior and/or Mood: Melatonin vs Placebo, Outcome 6 Cohen‐Mansfield Agitation Inventory Score at final endpoint measure (6 weeks, 2.5 mg MLT).
2.7
2.7. Analysis
Comparison 2 Behavior and/or Mood: Melatonin vs Placebo, Outcome 7 Cohen‐Mansfield Agitation Inventory Score at final endpoint measure (1 year, 2.5 mg MLT).
2.8
2.8. Analysis
Comparison 2 Behavior and/or Mood: Melatonin vs Placebo, Outcome 8 Cohen‐Mansfield Agitation Inventory Score at final endpoint measure (2 years, 2.5 mg MLT).
2.9
2.9. Analysis
Comparison 2 Behavior and/or Mood: Melatonin vs Placebo, Outcome 9 Behavior and Mood score in Multi Observation Scale for Elderly Subjects at final endpoint measure (6 weeks, 2.5 mg MLT).
2.10
2.10. Analysis
Comparison 2 Behavior and/or Mood: Melatonin vs Placebo, Outcome 10 Behavior and Mood score in Multi Observation Scale for Elderly Subjects at final endpoint measure (1 year, 2.5 mg MLT).
2.11
2.11. Analysis
Comparison 2 Behavior and/or Mood: Melatonin vs Placebo, Outcome 11 Behavior and Mood score in Multi Observation Scale for Elderly Subjects at final endpoint measure (2 years, 2.5 mg MLT).
2.12
2.12. Analysis
Comparison 2 Behavior and/or Mood: Melatonin vs Placebo, Outcome 12 Cornell Depression Rating Scale Score for Dementia at final endpoint measure (6 weeks, 2.5 mg MLT).
2.13
2.13. Analysis
Comparison 2 Behavior and/or Mood: Melatonin vs Placebo, Outcome 13 Cornell Depression Rating Scale Score for Dementia at final endpoint measure (1 year, 2.5 mg MLT).
2.14
2.14. Analysis
Comparison 2 Behavior and/or Mood: Melatonin vs Placebo, Outcome 14 Cornell Depression Rating Scale Score for Dementia at final endpoint measure (2 years, 2.5 mg MLT).
2.15
2.15. Analysis
Comparison 2 Behavior and/or Mood: Melatonin vs Placebo, Outcome 15 Mood Score in Philadelphia Geriatric Centre Rating Scale (positive) at final endpoint measure (6 weeks, 2.5 mg MLT).
2.16
2.16. Analysis
Comparison 2 Behavior and/or Mood: Melatonin vs Placebo, Outcome 16 Mood score in Philadelphia Geriatric Centre Affect Rating Scale (positive) at final endpoint measure (1 year, 2.5 mg MLT).
2.17
2.17. Analysis
Comparison 2 Behavior and/or Mood: Melatonin vs Placebo, Outcome 17 Mood score in Philadelphia Geriatric Centre Affect Rating Scale (positive) at final endpoint measure (2 years, 2.5 mg MLT).
2.18
2.18. Analysis
Comparison 2 Behavior and/or Mood: Melatonin vs Placebo, Outcome 18 Mood score in Philadelphia Geriatric Centre Affect Rating Scale (negative) at final endpoint measure (6 weeks, 2.5 mg MLT).
2.19
2.19. Analysis
Comparison 2 Behavior and/or Mood: Melatonin vs Placebo, Outcome 19 Mood score in Philadelphia Geriatric Centre Affect Rating Scale (negative) at final endpoint measure (1 year, 2.5 mg MLT).
2.20
2.20. Analysis
Comparison 2 Behavior and/or Mood: Melatonin vs Placebo, Outcome 20 Mood score in Philadelphia Geriatric Centre Affect Rating Scale (negative) at final endpoint measure (2 years, 2.5 mg MLT).
2.21
2.21. Analysis
Comparison 2 Behavior and/or Mood: Melatonin vs Placebo, Outcome 21 Mood score in Philadelphia Geriatric Centre Morale Scale at final endpoint measure (6 weeks, 2.5 mg MLT).
2.22
2.22. Analysis
Comparison 2 Behavior and/or Mood: Melatonin vs Placebo, Outcome 22 Mood score in Philadelphia Geriatric Centre Morale Scale at final endpoint measure (1 year, 2.5 mg MLT).
2.23
2.23. Analysis
Comparison 2 Behavior and/or Mood: Melatonin vs Placebo, Outcome 23 Mood score in Philadelphia Geriatric Centre Morale Scale at final endpoint measure (2 years, 2.5 mg MLT).
3.1
3.1. Analysis
Comparison 3 Functions of Daily Living: Melatonin vs Placebo, Outcome 1 ADL score at final endpoint measure (6 weeks, 2.5 mg MLT).
3.2
3.2. Analysis
Comparison 3 Functions of Daily Living: Melatonin vs Placebo, Outcome 2 ADL score at final endpoint measure (1 year, 2.5 mg MLT).
3.3
3.3. Analysis
Comparison 3 Functions of Daily Living: Melatonin vs Placebo, Outcome 3 ADL score at final endpoint measure (2 years, 2.5 mg MLT).
4.1
4.1. Analysis
Comparison 4 Sensitivity Analysis: MMSE Cognition Score, Outcome 1 MMSE Cognition Score at endpoint from baseline (change scores at 4 weeks, 3 mg MLT; 7 weeks, 2.5 mg MLT).
5.1
5.1. Analysis
Comparison 5 Adverse Events (AE):Melatonin vs Placebo, Outcome 1 Mean Number of AE Reports per Person (Melatonin 2.5 mg at 7 weeks).
5.2
5.2. Analysis
Comparison 5 Adverse Events (AE):Melatonin vs Placebo, Outcome 2 Mean AE Severity (Melatonin 2.5 mg at 7 weeks).
5.3
5.3. Analysis
Comparison 5 Adverse Events (AE):Melatonin vs Placebo, Outcome 3 Mean AE Seriousness (Melatonin 2.5 mg at 7 weeks).
5.4
5.4. Analysis
Comparison 5 Adverse Events (AE):Melatonin vs Placebo, Outcome 4 Mean AE Relatedness to Melatonin (Melatonin 2.5 mg at 7 weeks).
5.5
5.5. Analysis
Comparison 5 Adverse Events (AE):Melatonin vs Placebo, Outcome 5 Mean Number of AE Reports per Person (Melatonin 10 mg at 7 weeks).
5.6
5.6. Analysis
Comparison 5 Adverse Events (AE):Melatonin vs Placebo, Outcome 6 Mean AE Severity (Melatonin 10 mg at 7 weeks).
5.7
5.7. Analysis
Comparison 5 Adverse Events (AE):Melatonin vs Placebo, Outcome 7 Mean AE Seriousness (Melatonin 10 mg at 7 weeks).
5.8
5.8. Analysis
Comparison 5 Adverse Events (AE):Melatonin vs Placebo, Outcome 8 Mean AE Relatedness (Melatonin 10 mg at 7 weeks).
6.1
6.1. Analysis
Comparison 6 Adverse Effects: Melatonin vs Placebo, Outcome 1 Mean Adverse Effect Ratings for Dizziness (Melatonin 2.5 mg over 3.5 years follow‐up).
6.2
6.2. Analysis
Comparison 6 Adverse Effects: Melatonin vs Placebo, Outcome 2 Mean Adverse Effect Ratings for Drowsiness (Melatonin 2.5 mg over 3.5 years follow‐up).
6.3
6.3. Analysis
Comparison 6 Adverse Effects: Melatonin vs Placebo, Outcome 3 Mean Adverse Effect Ratings for Eye Complaints (Melatonin 2.5 mg over 3.5 years follow‐up).
6.4
6.4. Analysis
Comparison 6 Adverse Effects: Melatonin vs Placebo, Outcome 4 Mean Adverse Effect Ratings for Feebleness (Melatonin 2.5 mg over 3.5 years follow‐up).
6.5
6.5. Analysis
Comparison 6 Adverse Effects: Melatonin vs Placebo, Outcome 5 Mean Adverse Effect Ratings for Headache (Melatonin 2.5 mg over 3.5 years follow‐up).
6.6
6.6. Analysis
Comparison 6 Adverse Effects: Melatonin vs Placebo, Outcome 6 Mean Adverse Effect Ratings for Hunger (Melatonin 2.5 mg over 3.5 years follow‐up).
6.7
6.7. Analysis
Comparison 6 Adverse Effects: Melatonin vs Placebo, Outcome 7 Mean Adverse Effect Ratings for Hyperactivity (Melatonin 2.5 mg over 3.5 years follow‐up).
6.8
6.8. Analysis
Comparison 6 Adverse Effects: Melatonin vs Placebo, Outcome 8 Mean Adverse Effect Ratings for Inability to Sleep (Melatonin 2.5 mg over 3.5 years follow‐up).
6.9
6.9. Analysis
Comparison 6 Adverse Effects: Melatonin vs Placebo, Outcome 9 Mean Adverse Effect Ratings for Irritability (Melatonin 2.5 mg over 3.5 years follow‐up).
6.10
6.10. Analysis
Comparison 6 Adverse Effects: Melatonin vs Placebo, Outcome 10 Mean Adverse Effect Ratings for Nausea (Melatonin 2.5 mg over 3.5 years follow‐up).
6.11
6.11. Analysis
Comparison 6 Adverse Effects: Melatonin vs Placebo, Outcome 11 Mean Adverse Effect Ratings for Constipation (Melatonin 2.5 mg over 3.5 years follow‐up).
6.12
6.12. Analysis
Comparison 6 Adverse Effects: Melatonin vs Placebo, Outcome 12 Mean Adverse Effect Ratings for Pins and Needles (Melatonin 2.5 mg over 3.5 years follow‐up).
6.13
6.13. Analysis
Comparison 6 Adverse Effects: Melatonin vs Placebo, Outcome 13 Mean Adverse Effect Ratings for Stomach Ache (Melatonin 2.5 mg over 3.5 years follow‐up).
6.14
6.14. Analysis
Comparison 6 Adverse Effects: Melatonin vs Placebo, Outcome 14 Mean Adverse Effect Ratings for Sweating (Melatonin 2.5 mg over 3.5 years follow‐up).
6.15
6.15. Analysis
Comparison 6 Adverse Effects: Melatonin vs Placebo, Outcome 15 Mean Adverse Effect Ratings for Trembling Hands (Melatonin 2.5 mg over 3.5 years follow‐up).
6.16
6.16. Analysis
Comparison 6 Adverse Effects: Melatonin vs Placebo, Outcome 16 Mean Adverse Effect Ratings for Other Complications.
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Update of

References

References to studies included in this review

Asayama 2003 {published and unpublished data}
    1. Asayama K, Yamadera H, Ito T, Suzuki H, Kudo Y, Endo S. Double blind study of melatonin effects on the sleep‐wake rhythm, cognitive and non‐cognitive functions in Alzheimer type dementia. Journal of Nippon Medical School; Nihon Ika Daigaku zasshi 2003;70(4):334‐41. - PubMed
Gehrman 2009 {published data only}
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Singer 2003 {published and unpublished data}
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Baskett 2003 {published data only}
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Bourne 2006 {unpublished data only}
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Furio 2007 {published data only}
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Haffmans 2001 {published data only}
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Riemersma‐van der Lek 2005 {unpublished data only}
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Savaskan 2006 {published data only}
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