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Scientific Reports Jul 20176-Sulfatoxymelatonin (aMT6s) is the main metabolite of melatonin in urine, and is a reliable surrogate biomarker reflecting the blood melatonin concentration. This... (Meta-Analysis)
Meta-Analysis
6-Sulfatoxymelatonin (aMT6s) is the main metabolite of melatonin in urine, and is a reliable surrogate biomarker reflecting the blood melatonin concentration. This meta-analysis assessed the association between urinary aMT6s level and BC incidence. The electronic databases PubMed, EMBASE, Cochrane Library, and Web of Science were searched. Risk ratios (RRs) were adopted to estimate the relative BC incidence. A total of 7 prospective case-control publications were included, and 6 of them were distinct studies. Pooled analysis of data from the 6 studies involving 1824 women with incident BC and 3954 matched control participants with no overlapping of subjects among studies indicated no significant association between the highest levels of urinary aMT6s and the incidence of BC (RR = 0.97, 95% CI, 0.88-1.08, P = 0.56). Negative associations were observed in postmenopausal women (RR = 0.88, 95% CI, 0.75-1.02, P = 0.10), estrogen receptor positive BC (RR = 0.83, 95% CI, 0.64-1.07, P = 0.15), and studies using 12-hour overnight urine (RR = 0.81, 95% CI, 0.61-1.07, P = 0.13), all with borderline significances. Lag time or invasive degree did not interfere with the results. There was no evident publication bias detected by the Egger's test and the funnel plot. Conclusively, the current evidence did not support a significant association between urinary aMT6s level and BC risk.
Topics: Breast Neoplasms; Humans; Incidence; Melatonin; Prospective Studies; Risk Assessment
PubMed: 28706222
DOI: 10.1038/s41598-017-05752-9 -
Pain Physician 2015Adolescent idiopathic scoliosis (AIS) is a tridimensional structural deformity of the spine that may deteriorate progressively, leading to significant functional... (Meta-Analysis)
Meta-Analysis Review
The Association of rs4753426 Polymorphism in the Melatonin Receptor 1B (MTNR1B) Gene and Susceptibility to Adolescent Idiopathic Scoliosis: A Systematic Review and Meta-analysis.
BACKGROUND
Adolescent idiopathic scoliosis (AIS) is a tridimensional structural deformity of the spine that may deteriorate progressively, leading to significant functional limitations and pain problems. Several previous studies have implicated the rs4753426 single nucleotide polymorphism in the melatonin receptor 1B (MTNR1B) gene in the etiology of AIS. However the sample sizes were limited and the findings of those studies were inconsistent. An overall assessment of the evidence supporting this association has not been previously conducted.
OBJECTIVES
To provide a comprehensive assessment and synthesis of the currently available evidence on the association between rs4753426 and AIS.
STUDY DESIGN
A systematic review and meta-analysis.
SETTING
University hospital, China.
METHODS
This review followed the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. PubMed (MEDLINE), EMBASE, Scopus databases, and WANFANG databases were systematically searched through December 2014 to identify relevant studies following a sensitive strategy. Statistical analysis was performed using the Review Manager 5.2 software. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using the fixed-effect inverse variance model for allelic (C vs. T) and genotypic comparisons.
RESULTS
Four papers including 5 studies which involved 2,552 AIS cases and 2,738 controls were identified for this meta-analysis. The results showed that C allele of the rs4753426 was significantly associated with AIS (OR = 1.12, 95% CI: 1.03-1.21, P = 0.01). CT and CC genotypes were 26% (OR = 1.26, 95% CI: 1.04-1.53, P = 0.01) and 28% (OR = 1.28, 95% CI: 1.05-1.56, P = 0.01), respectively, more likely to have AIS compared with CC genotype. As for the dominant model (CC+TT vs. TT), summary ORs showed statistically significant association with AIS (OR = 1.28, 95% CI: 1.06-1.53, P = 0.009). Compared with the CT+TT genotype, the summary ORs of the CC genotype showed marginally statistically significant association with AIS (OR = 1.11, 95 % CI: 0.99-1.24, P = 0.07). The subgroup meta-analysis results showed the C allele and each genotype were significantly associated with AIS in the Asian group but not in the Caucasian group.
LIMITATIONS
Paucity of available literature.
CONCLUSIONS
To our knowledge, there has been no meta-analysis to analyze the association between rs4753426 polymorphism in the MTNR1B gene and AIS. This systematic review was a comprehensive analysis of the currently available evidence, and found an overall significant association of rs4753426 polymorphism with the risk of AIS, especially in the Asian population. Further investigation of this association is necessary in other populations.
Topics: Adolescent; Asian People; Gene Frequency; Genetic Predisposition to Disease; Humans; Polymorphism, Genetic; Receptor, Melatonin, MT2; Scoliosis
PubMed: 26431121
DOI: No ID Found -
World Journal of Orthopedics Aug 2015To evaluate published data on the predictors of progressive adolescent idiopathic scoliosis (AIS) in order to evaluate their efficacy and level of evidence.
AIM
To evaluate published data on the predictors of progressive adolescent idiopathic scoliosis (AIS) in order to evaluate their efficacy and level of evidence.
SELECTION CRITERIA
(1) study design: randomized controlled clinical trials, prospective cohort studies and case series, retrospective comparative and none comparative studies; (2) participants: adolescents with AIS aged from 10 to 20 years; and (3) treatment: observation, bracing, and other.
SEARCH METHOD
Ovid MEDLINE, Embase, the Cochrane Library, PubMed and patent data bases. All years through August 2014 were included. Data were collected that showed an association between the studied characteristics and the progression of AIS or the severity of the spine deformity. Odds ratio (OR), sensitivity, specificity, positive and negative predictive values were also collected. A meta-analysis was performed to evaluate the pooled OR and predictive values, if more than 1 study presented a result. The GRADE approach was applied to evaluate the level of evidence.
RESULTS
The review included 25 studies. All studies showed statistically significant or borderline association between severity or progression of AIS with the following characteristics: (1) An increase of the Cobb angle or axial rotation during brace treatment; (2) decrease of the rib-vertebral angle at the apical level of the convex side during brace treatment; (3) initial Cobb angle severity (> 25(o)); (4) osteopenia; (5) patient age < 13 years at diagnosis; (6) premenarche status; (7) skeletal immaturity; (8) thoracic deformity; (9) brain stem vestibular dysfunction; and (10) multiple indices combining radiographic, demographic, and physiologic characteristics. Single nucleotide polymorphisms of the following genes: (1) calmodulin 1; (2) estrogen receptor 1; (3) tryptophan hydroxylase 1; (3) insulin-like growth factor 1; (5) neurotrophin 3; (6) interleukin-17 receptor C; (7) melatonin receptor 1B, and (8) ScoliScore test. Other predictors included: (1) impairment of melatonin signaling in osteoblasts and peripheral blood mononuclear cells (PBMC); (2) G-protein signaling dysfunction in PBMC; and (3) the level of platelet calmodulin. However, predictive values of all these findings were limited, and the levels of evidence were low. The pooled result of brace treatment outcomes demonstrated that around 27% of patents with AIS experienced exacerbation of the spine deformity during or after brace treatment, and 15% required surgical correction. However, the level of evidence is also low due to the limitations of the included studies.
CONCLUSION
This review did not reveal any methods for the prediction of progression in AIS that could be recommended for clinical use as diagnostic criteria.
PubMed: 26301183
DOI: 10.5312/wjo.v6.i7.537 -
Scientific Reports Aug 2014Studies have investigated the relationship between genetic variants and risk of gestational diabetes mellitus (GDM). However, the results remain inconclusive. The aim of... (Meta-Analysis)
Meta-Analysis Review
Studies have investigated the relationship between genetic variants and risk of gestational diabetes mellitus (GDM). However, the results remain inconclusive. The aim of this study was to investigate the association of rs10830963 and rs1387153 variants in melatonin receptor 1B (MTNR1B) and rs1801278 variant in insulin receptor substrate 1 (IRS1) with GDM susceptibility. Electronic database of PubMed, Medline, Embase, and CNKI (China National Knowledge Infrastructure) were searched for relevant studies between 2005 and 2014. The odds ratio (OR) with its 95% confidence interval (CI) were employed to estimate the association. Total ten case-control studies, including 3428 GDM cases and 4637 healthy controls, met the inclusion criteria. Our results showed a significant association between the three genetic variants and GDM risk, rs10830963 with a P-value less than 0.0001, rs1387153 with a P-value of 0.0002, and rs1801278 with a P-value of 0.001. Furthermore, all the genetic models in these three polymorphisms were associated with increased risks of GDM as well (P< = 0.009). In conclusion, our study found that the genetic polymorphisms rs10830963 and rs1387153 in MTNR1B and rs1801278 in IRS1 were associated with an increased risk of developing GDM. However, further studies with gene-gene and gene-environmental interactions should be considered.
Topics: Alleles; Diabetes, Gestational; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Humans; Insulin Receptor Substrate Proteins; Odds Ratio; Polymorphism, Genetic; Pregnancy; Publication Bias; Receptor, Melatonin, MT2
PubMed: 25146448
DOI: 10.1038/srep06113 -
Sleep Medicine Apr 2014Ramelteon is the first selective melatonin receptor agonist and currently is approved in the United States and Japan for the treatment of insomnia. Our meta-analysis... (Meta-Analysis)
Meta-Analysis Review
Ramelteon is the first selective melatonin receptor agonist and currently is approved in the United States and Japan for the treatment of insomnia. Our meta-analysis assessed the efficacy and safety of ramelteon for the treatment of insomnia in adults. We included both published and unpublished data from randomized placebo-controlled trials evaluating the efficacy of ramelteon in adults with insomnia in the analysis. Our primary outcomes were sleep quality, subjective sleep latency (sSL), and subjective total sleep time (sTST). Secondary outcomes included latency to persistent sleep (LPS), total sleep time (TST), sleep efficiency (SE), proportion of rapid eye movement (REM) sleep, wakefulness after sleep onset (WASO), subjective WASO, number of nighttime awakenings (NAW), subjective NAW, and adverse events. Thirteen trials involving 5812 patients with insomnia or insomnia symptoms with a mean study duration of 38 days were pooled. Ramelteon was associated with reduced sSL (weighted mean difference [WMD], -4.30 min [95% confidence interval {CI}, -7.01 to -1.58]) and improved sleep quality (standardized mean differences, -0.074 [95% CI, -0.13 to -0.02]) but was not associated with increased sTST. Ramelteon also was associated with improvement in LPS, SE, and TST. The only significant adverse event was somnolence. Short-term use of ramelteon was associated with improvement in some sleep parameters in patients with insomnia, but its clinical impact is small. Long-term trials are needed before solid conclusions can be established.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Female; Humans; Indenes; Male; Middle Aged; Randomized Controlled Trials as Topic; Receptors, Melatonin; Sleep; Sleep Initiation and Maintenance Disorders; Treatment Outcome; Young Adult
PubMed: 24656909
DOI: 10.1016/j.sleep.2013.11.788 -
The Cochrane Database of Systematic... Dec 2013Major depressive disorder (MDD), or depression, is a syndrome characterised by a number of behavioural, cognitive and emotional features. It is most commonly associated... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Major depressive disorder (MDD), or depression, is a syndrome characterised by a number of behavioural, cognitive and emotional features. It is most commonly associated with a sad or depressed mood, a reduced capacity to feel pleasure, feelings of hopelessness, loss of energy, altered sleep patterns, weight fluctuations, difficulty in concentrating and suicidal ideation. There is a need for more effective and better tolerated antidepressants to combat this condition. Agomelatine was recently added to the list of available antidepressant drugs; it is a novel antidepressant that works on melatonergic (MT1 and MT2), 5-HT 2B and 5-HT2C receptors. Because the mechanism of action is claimed to be novel, it may provide a useful, alternative pharmacological strategy to existing antidepressant drugs.
OBJECTIVES
The objective of this review was 1) to determine the efficacy of agomelatine in alleviating acute symptoms of major depressive disorder in comparison with other antidepressants, 2) to review the acceptability of agomelatine in comparison with other antidepressant drugs, and, 3) to investigate the adverse effects of agomelatine, including the general prevalence of side effects in adults.
SEARCH METHODS
We searched the Cochrane Collaboration's Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR) to 31 July 2013. The CCDANCTR includes relevant randomised controlled trials from the following bibliographic databases: CENTRAL (the Cochrane Central Register of Controlled Trials) (all years), EMBASE (1974 onwards), MEDLINE (1950 onwards) and PsycINFO (1967 onwards). We checked reference lists of relevant studies together with reviews and regulatory agency reports. No restrictions on date, language or publication status were applied to the search. Servier Laboratories (developers of agomelatine) and other experts in the field were contacted for supplemental data.
SELECTION CRITERIA
Randomised controlled trials allocating adult participants with major depression to agomelatine versus any other antidepressive agent.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and a double-entry procedure was employed. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy, acceptability and tolerability.
MAIN RESULTS
A total of 13 studies (4495 participants) were included in this review. Agomelatine was compared to selective serotonin reuptake inhibitors (SSRIs), namely paroxetine, fluoxetine, sertraline, escitalopram, and to the serotonin-norepinephrine reuptake inhibitor (SNRI), venlafaxine. Participants were followed up for six to 12 weeks. Agomelatine did not show any advantage or disadvantage over the other antidepressants for our primary outcome, response to treatment (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.95 to 1.08, P value 0.75 compared to SSRIs, and RR 1.06; 95% CI 0.98 to 1.16, P value 0.16 compared to venlafaxine). Also, agomelatine showed no advantage or disadvantage over other antidepressants for remission (RR 0.83; 95% CI 0.68 to 1.01, P value 0.07 compared to SSRIs, and RR 1.08; 95% CI 0.94 to 1.24, P value 0.73 compared to venlafaxine). Overall, agomelatine appeared to be better tolerated than venlafaxine in terms of lower rates of drop outs (RR 0.40; 95% CI 0.24 to 0.67, P value 0.0005), and showed the same level of tolerability as SSRIs (RR 0.95; 95% CI 0.83 to 1.09, P value 0.44). Agomelatine induced a lower rate of dizziness than venlafaxine (RR 0.19, 95% CI 0.06 to 0.64, P value 0.007).With regard to the quality of the body of evidence, there was a moderate risk of bias for all outcomes, due to the number of included unpublished studies. There was some heterogeneity, particularly between published and unpublished studies. The included studies were conducted in inpatient and outpatient settings, thus limiting the generalisability of the results to primary care settings. With regard to precision, the efficacy outcomes were precise, but the tolerability outcomes were mostly imprecise. Publication bias was variable and depended on the outcome of the trial. Our review included unpublished studies, and we think that this reduced the impact of publication bias. The overall methodological quality of the studies was not very good. Almost all of the studies were sponsored by the pharmaceutical company that manufactures agomelatine (Servier), and some of these were unpublished. Attempts to contact the pharmaceutical company Servier for additional information on all unpublished studies were unsuccessful.
AUTHORS' CONCLUSIONS
Agomelatine did not seem to provide a significant advantage in efficacy over other antidepressive agents for the acute-phase treatment of major depression. Agomelatine was better tolerated than paroxetine and venlafaxine in terms of overall side effects, and fewer participants treated with agomelatine dropped out of the trials due to side effects compared to sertraline and venlafaxine, but data were limited because the number of included studies was small. We found evidence that compared agomelatine with only a small number of other active antidepressive agents, and there were only a few trials for each comparison, which limits the generalisability of the results. Moreover, the overall methodological quality of the studies was low, and, therefore, no firm conclusions can be drawn concerning the efficacy and tolerability of agomelatine.
Topics: Acetamides; Adult; Antidepressive Agents; Depressive Disorder, Major; Humans; Melatonin; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors
PubMed: 24343836
DOI: 10.1002/14651858.CD008851.pub2 -
Human Reproduction Update 2013Several studies have examined associations between genetic variants and the risk of gestational diabetes mellitus (GDM). However, inferences from these studies were... (Review)
Review
BACKGROUND
Several studies have examined associations between genetic variants and the risk of gestational diabetes mellitus (GDM). However, inferences from these studies were often hindered by limited statistical power and conflicting results. We aimed to systematically review and quantitatively summarize the association of commonly studied single nucleotide polymorphisms (SNPs) with GDM risk and to identify important gaps that remain for consideration in future studies.
METHODS
Genetic association studies of GDM published through 1 October 2012 were searched using the HuGE Navigator and PubMed databases. A SNP was included if the SNP-GDM associations were assessed in three or more independent studies. Two reviewers independently evaluated the eligibility for inclusion and extracted the data. The allele-specific odds ratios (ORs) and 95% confidence intervals (CIs) were pooled using random effects models accounting for heterogeneity.
RESULTS
Overall, 29 eligible articles capturing associations of 12 SNPs from 10 genes were included for the systematic review. The minor alleles of rs7903146 (TCF7L2), rs12255372 (TCF7L2), rs1799884 (-30G/A, GCK), rs5219 (E23K, KCNJ11), rs7754840 (CDKAL1), rs4402960 (IGF2BP2), rs10830963 (MTNR1B), rs1387153 (MTNR1B) and rs1801278 (Gly972Arg, IRS1) were significantly associated with a higher risk of GDM. Among them, genetic variants in TCF7L2 showed the strongest association with GDM risk, with ORs (95% CIs) of 1.44 (1.29-1.60, P < 0.001) per T allele of rs7903146 and 1.46 (1.15-1.84, P = 0.002) per T allele of rs12255372.
CONCLUSIONS
In this systematic review, we found significant associations of GDM risk with nine SNPs in seven genes, most of which have been related to the regulation of insulin secretion.
Topics: Alleles; Cyclin-Dependent Kinase 5; Diabetes, Gestational; Female; Humans; Insulin; Insulin Receptor Substrate Proteins; Insulin Secretion; Polymorphism, Single Nucleotide; Pregnancy; RNA-Binding Proteins; Receptor, Melatonin, MT1; Receptor, Melatonin, MT2; Risk; Transcription Factor 7-Like 2 Protein; tRNA Methyltransferases
PubMed: 23690305
DOI: 10.1093/humupd/dmt013 -
Expert Opinion on Drug Metabolism &... Apr 2013The high prevalence of irritable bowel syndrome (IBS), a chronic gastrointestinal (GI) disorder, its lack of satisfactory effective drugs and its complicated... (Review)
Review
INTRODUCTION
The high prevalence of irritable bowel syndrome (IBS), a chronic gastrointestinal (GI) disorder, its lack of satisfactory effective drugs and its complicated pathophysiology lead to the demand of new therapeutic agents. During a new drug development process, the pharmacokinetic profiling is of a great considerable importance comparable to drug's efficacy. This involves the drug's absorption, distribution, metabolism and excretion, all of which are crucial to its usefulness. In addition, the toxicological profile and possible adverse reactions of the drug should be identified. Also its interactions should be identified at different phases of trials. Several pharmacokinetic studies are carried out to achieve drugs with the best absorption and bioavailability and the least adverse effects and lowest toxicity.
AREAS COVERED
To make an update on new clinically introduced drugs for IBS and their dynamics and kinetics data, the present systematic review was accomplished. All relevant bibliographic databases were searched from the year 2003 up to May 2012 to identify all clinical trials that evaluated the potential efficacy of a novel agent in IBS.
EXPERT OPINION
Some evaluated drugs, such as ramosetron (5-HT3 antagonist) and pexacerfont (CRF1 receptor antagonist), have shown some benefits in diarrhea-predominant IBS (D-IBS), while, prucalopride and mosapride (5-HT4 agonist) with prokinetic effect were found useful in constipation-predominant IBS (C-IBS). Besides, dexloxiglumide, lubiprostone and linaclotide have shown beneficial effects in C-IBS patients. Melatonin regulates GI tract motility and, asimadoline, gabapentin and pregabalin show reduction of pain threshold and visceral hypersensitivity. Glucagon-like peptide analog, calcium-channel blockers and neurokinin receptor antagonists have shown benefits in pain attacks. More time is required to indicate both efficacy and safety in long-term treatment due to multifactorial pathophysiology, variations in individual responses and insufficient assessment methods, which limit the right decision-making process about the efficacy and tolerability of these new drugs.
Topics: Analgesics; Anti-Bacterial Agents; Antidepressive Agents; Dietary Fiber; Drugs, Chinese Herbal; Humans; Irritable Bowel Syndrome; Parasympatholytics; Probiotics; Randomized Controlled Trials as Topic
PubMed: 23330973
DOI: 10.1517/17425255.2013.759558 -
International Journal of Clinical... Sep 2012As a melatonin receptor agonist, ramelteon has been approved in the United States as a treatment for insomnia. As a potential alternation, ramelteon should be further... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
As a melatonin receptor agonist, ramelteon has been approved in the United States as a treatment for insomnia. As a potential alternation, ramelteon should be further evaluated in different doses and populations. This systematic review with meta-analysis aims to determine the efficacy and safety of ramelteon in the treatment of chronic insomnia.
METHODS
We systematically searched and identified in Medline, Embase, PsycINFO and Cochrane Library until September 2011. We only included randomised controlled trials focused on ramelteon, vs. placebo, or any other treatment for patients with chronic insomnia. Data were extracted and evaluated by two independent investigators. If neither clinical nor statistical heterogeneity was found, we pooled results using a fixed-effect model.
RESULTS
Eight studies were selected to include from 175 identified references. There were significant improvements in all the outcomes (subjective and polysomnographic sleep latency, total sleep time and latency to REM), except for the percentage of REM. By subgroup analysis, subjective sleep latency was reduced only in the patients of 18-64 years old, without in the patients over 65 years old. For the safety, ramelteon was not associated with higher risk ratio of any frequent adverse events comparing with control.
CONCLUSION
The efficacy and safety of ramelteon are promising for the chronic insomnia patients. More researches are required for robust conclusions, particularly well-designed; double-blind randomised controlled trials with higher doses of ramelteon (32 or 64 mg) for the older population comparing with other sedative hypnotics.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Double-Blind Method; Humans; Hypnotics and Sedatives; Indenes; Middle Aged; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders; Treatment Outcome; Young Adult
PubMed: 22897464
DOI: 10.1111/j.1742-1241.2012.02987.x -
Developmental Medicine and Child... Sep 2011The aim of this study was to investigate melatonin-related findings in autism spectrum disorders (ASD), including autistic disorder, Asperger syndrome, Rett syndrome,... (Meta-Analysis)
Meta-Analysis Review
AIM
The aim of this study was to investigate melatonin-related findings in autism spectrum disorders (ASD), including autistic disorder, Asperger syndrome, Rett syndrome, and pervasive developmental disorders, not otherwise specified.
METHOD
Comprehensive searches were conducted in the PubMed, Google Scholar, CINAHL, EMBASE, Scopus, and ERIC databases from their inception to October 2010. Two reviewers independently assessed 35 studies that met the inclusion criteria. Of these, meta-analysis was performed on five randomized double-blind, placebo-controlled studies, and the quality of these trials was assessed using the Downs and Black checklist.
RESULTS
Nine studies measured melatonin or melatonin metabolites in ASD and all reported at least one abnormality, including an abnormal melatonin circadian rhythm in four studies, below average physiological levels of melatonin and/or melatonin derivates in seven studies, and a positive correlation between these levels and autistic behaviors in four studies. Five studies reported gene abnormalities that could contribute to decreased melatonin production or adversely affect melatonin receptor function in a small percentage of children with ASD. Six studies reported improved daytime behavior with melatonin use. Eighteen studies on melatonin treatment in ASD were identified; these studies reported improvements in sleep duration, sleep onset latency, and night-time awakenings. Five of these studies were randomized double-blind, placebo-controlled crossover studies; two of the studies contained blended samples of children with ASD and other developmental disorders, but only data for children with ASD were used in the meta-analysis. The meta-analysis found significant improvements with large effect sizes in sleep duration (73 min compared with baseline, Hedge's g 1.97 [95% confidence interval {CI} CI 1.10-2.84], Glass's Δ 1.54 [95% CI 0.64-2.44]; 44 min compared with placebo, Hedge's g 1.07 [95% CI 0.49-1.65], Glass's Δ 0.93 [95% CI 0.33-1.53]) and sleep onset latency (66 min compared with baseline, Hedge's g-2.42 [95% CI -1.67 to -3.17], Glass's Δ-2.18 [95% CI -1.58 to -2.76]; 39 min compared with placebo, Hedge's g-2.46 [95% CI -1.96 to -2.98], Glass's Δ-1.28 [95% CI -0.67 to -1.89]) but not in night-time awakenings. The effect size varied significantly across studies but funnel plots did not indicate publication bias. The reported side effects of melatonin were minimal to none. Some studies were affected by limitations, including small sample sizes and variability in the protocols that measured changes in sleep parameters.
INTERPRETATION
Melatonin administration in ASD is associated with improved sleep parameters, better daytime behavior, and minimal side effects. Additional studies of melatonin would be helpful to confirm and expand on these findings.
Topics: Child; Child Development Disorders, Pervasive; Child, Preschool; Databases, Factual; Double-Blind Method; Humans; Melatonin; Randomized Controlled Trials as Topic
PubMed: 21518346
DOI: 10.1111/j.1469-8749.2011.03980.x