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CNS Drugs Apr 2022Bipolar disorder (BD) is a chronic relapsing-remitting psychiatric disorder. Sleep and circadian rhythm disturbances persist during acute mood episodes of the disorder... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bipolar disorder (BD) is a chronic relapsing-remitting psychiatric disorder. Sleep and circadian rhythm disturbances persist during acute mood episodes of the disorder and during euthymia. However, the treatment potential of hypnotic agents that might be used to manage sleep disturbance in BD is not well understood. Similarly, melatonin and medications with a melatonin-receptor agonist mechanism of action may have chronotherapeutic potential for treating people with the disorder, but the impact of these substances on sleep and circadian rhythms and core symptoms in BD is unclear.
OBJECTIVE
Our aim was to conduct a systematic review and meta-analysis evaluating the current evidence for hypnotic and melatonin/melatonin-receptor agonist pharmacotherapy for symptoms of sleep disturbance, mania, and depression in patients with BD.
METHODS
AMED, Embase, MEDLINE and PsychINFO databases were searched for studies published in English from the date of inception to 31 October 2021. Studies included in this review were randomised controlled trials (RCTs) and non-controlled/non-randomised studies for BD that examined hypnotic medications selected based on a common pattern of usage for treating insomnia (i.e. chloral, clomethiazole, diphenhydramine, doxepin, doxylamine, promethazine, suvorexant, zaleplon, zolpidem, zopiclone, and eszopiclone) and melatonin and the melatonin-receptor agonist drugs ramelteon and agomelatine. Risk of bias was assessed using the RoB2 and AXIS tools. Pooled effect sizes for RCT outcomes were estimated using random-effects models.
RESULTS
A total of eleven studies (six RCTs and five experimental feasibility studies) involving 1279 participants were included. Each study examined melatonin or melatonin-receptor agonists. No studies of hypnotics were found that fulfilled the review inclusion criteria. Pilot feasibility studies suggested beneficial treatment effects for symptoms of sleep disturbance, depression, and mania. However, the pooled effect of the two available RCT studies assessing sleep quality via Pittsburgh Sleep Quality Index scores was not statistically significant (g = - 0.04 [95% CI - 0.81 to 0.73]) and neither was the pooled effect for depressive symptoms (four studies; g = - 0.10 [95% CI - 0.27 to 0.08]). Some RCT evidence suggests ramelteon might prevent relapse into depression in BD. The largest efficacy signal detected was for manic symptoms (four studies; g = - 0.44 [95% CI - 1.03 to 0.14]) but there was substantial heterogeneity between studies and patient characteristics. In the two RCTs assessing manic symptoms during acute mania, adjunctive melatonin demonstrated superior treatment effects versus placebo.
CONCLUSIONS
There is a paucity of studies examining pharmacological interventions for sleep and circadian rhythm disturbance in BD. Few studies assessed sleep-related symptoms, and none quantitatively examined endogenous melatonin patterns or other circadian rhythms. Melatonin may be a promising candidate for the adjunctive treatment of bipolar mania. However, dose-finding studies and studies with larger sample sizes are needed to confirm its efficacy. We recommend parallel monitoring of sleep and circadian rhythms in future trials. Chronobiology-informed trial designs are needed to improve the quality of future studies.
PROTOCOL REGISTRATION
PROSPERO (CRD42020167528).
Topics: Bipolar Disorder; Humans; Hypnotics and Sedatives; Mania; Melatonin; Sleep; Sleep Wake Disorders
PubMed: 35305257
DOI: 10.1007/s40263-022-00911-7 -
Chronobiology International Oct 2021Blue-blocking glasses, also known as amber glasses, are plastic glasses that primarily block blue light. Blue-blocking glasses have been studied as a sleep intervention...
Blue-blocking glasses, also known as amber glasses, are plastic glasses that primarily block blue light. Blue-blocking glasses have been studied as a sleep intervention for insomnia, delayed sleep-phase disorder, shift work, jet lag, and nonpathologic sleep improvement. Blue-blocking glasses have also been studied as a treatment for bipolar disorder, major depression, and postpartum depression. Blue-blocking glasses improve sleep by inducing dim-light melatonin onset by reducing activation of intrinsically photosensitive retinal ganglion cells (ipRGCs) which are most sensitive to blue light and are a major input for circadian regulation; their mechanism for mood regulation is unclear but may be similar to that of dark therapy for bipolar disorder where patients are kept in darkness for an extended period every night. A systematic search of the scientific literature identified a total of 29 experimental publications involving evening wear of blue-blocking glasses for sleep or mood disorders. These consisted of 16 randomized controlled trials (RCTs) published in journals with a total of 453 patients, 5 uncontrolled trials, 1 case series, 1 case study, and 6 abstracts from conference proceedings. Only 1 case study and 1 RCT were for acutely manic patients but both found substantial decreases in manic symptoms with the use of blue-blocking glasses; these give preliminary clinical evidence of efficacy that makes blue-blocking glasses a high-yield intervention to study for bipolar disorder. Findings in the 3 publications for major depression and postpartum depression were heterogeneous and conflicting as to their efficacy. Out of the 24 publications focusing on sleep, there was substantial evidence for blue-blocking glasses being a successful intervention for reducing sleep onset latency in patients with sleep disorders, jet lag, or variable shift work schedules. Given the well-established biological mechanism and clinical research showing that blue-blocking glasses are effective for inducing sleep, they are a viable intervention to recommend to patients with insomnia or a delayed sleep phase.
Topics: Bipolar Disorder; Circadian Rhythm; Depressive Disorder, Major; Eyeglasses; Female; Humans; Light; Melatonin; Sleep
PubMed: 34030534
DOI: 10.1080/07420528.2021.1930029 -
Ophthalmic & Physiological Optics : the... Nov 2023Experimental models have implicated the role of melatonin circadian rhythm disruption in refractive error development. Recent studies have examined melatonin... (Review)
Review
PURPOSE
Experimental models have implicated the role of melatonin circadian rhythm disruption in refractive error development. Recent studies have examined melatonin concentration and its diurnal patterns on refractive error with equivocal results. This systematic review aimed to summarise the literature on melatonin circadian rhythms in myopia.
RECENT FINDINGS
PubMed, EMBASE, Web of Science, Scopus, ProQuest Central, LILACS, Cochrane and Medline databases were searched for papers between January 2010 and December 2022 using defined search terms. Seven studies measured melatonin and circadian rhythms in three biological fluids (blood serum, saliva and urine) in both myopes and non-myopes. Morning melatonin concentrations derived from blood serum varied significantly between studies in individuals aged 10-30 years, with a maximum of 89.45 pg/mL and a minimum of 5.43 pg/mL using liquid chromatography and mass spectrometry. The diurnal variation of salivary melatonin was not significantly different between myopes and emmetropes when measured every 4 h for 24 h and quantified with enzyme-linked immunosorbent assay. Significantly elevated salivary melatonin concentrations were reported in myopes compared with emmetropes, aged 18-30 years when measured hourly from evening until their habitual bedtime using liquid chromatography. However, the relationship between dim light melatonin onset and refractive group was inconsistent between studies. The 6-sulphatoxymelatonin concentration derived from overnight urine volume, measured using a double antibody radioimmunoassay, was found to be significantly lower in myopes (29.17 pg/mL) than emmetropes (42.51 pg/mL).
SUMMARY
The role of melatonin concentration and rhythm in myopia has not been studied extensively. This systematic review confirms conflicting findings across studies, with potential relationships existing. Future studies with uniform methodological approaches are required to ascertain the causal relationship between melatonin dysregulation and myopia in humans.
PubMed: 37568264
DOI: 10.1111/opo.13214 -
Clinical Nutrition ESPEN Jun 2023Melatonin is a pineal hormone with a complex role. It is linked to sleep, inflammatory, oxidative, and immunological processes. (Review)
Review
BACKGROUND
Melatonin is a pineal hormone with a complex role. It is linked to sleep, inflammatory, oxidative, and immunological processes.
AIM
To review the use of melatonin supplementation in rheumatological diseases.
METHODS
A systematic search of PubMed, Embase, and Scielo databases was performed, looking for articles on Melatonin and rheumatic diseases published between 1966 and August 2022.
RESULTS
Thirteen articles were identified: in fibromyalgia (n = 5 articles), rheumatoid arthritis (n = 2), systemic sclerosis (n = 1), systemic lupus erythematosus (n = 1) and osteoporosis/osteopenia (n = 3) and osteoarthritis (n = 1). There were positive results of melatonin administration in fibromyalgia, osteoarthritis, and osteoporosis/osteopenia but not in rheumatoid arthritis and lupus. The drug was well tolerated with mild side effects.
CONCLUSION
This review shows the efficacy of Melatonin in some rheumatic diseases. However, new studies are needed to elucidate the real role of this treatment in rheumatology.
Topics: Humans; Fibromyalgia; Melatonin; Arthritis, Rheumatoid; Rheumatic Diseases; Osteoarthritis; Osteoporosis; Dietary Supplements
PubMed: 37202076
DOI: 10.1016/j.clnesp.2023.04.011 -
Journal of Pineal Research Sep 2021Melatonin is involved in multiple changes that characterize the aging and can potentially be a safe and effective treatment for menopausal women. The aim of this study... (Review)
Review
Melatonin is involved in multiple changes that characterize the aging and can potentially be a safe and effective treatment for menopausal women. The aim of this study was to carry out a systematic review of the medical literature on the health benefits of oral melatonin administration on menopausal women. The electronic databases PubMed, Scopus, and Web of Science were searched systematically on interventional studies that evaluated the association between oral melatonin administration and the health of menopausal women. Risk for bias was assessed for randomized, controlled studies by the RoB v.2 tool and for non-randomized trials by the ROBINS-I tool. Twenty-four studies on melatonin treatment in various aspects of women's health were included in the final systematic review. The studies included 1,173 participants. No evidence was found for an independent effect of melatonin on hemodynamic measures or markers of glucose metabolism. There is some evidence that very low-density lipoprotein and triglycerides levels increase during melatonin administration. There is a fair amount of evidence that melatonin treatment has a favorable effect on bone density and BMI. Melatonin treatment improves EEG patterns and subjective sleep quality in postmenopausal women with preexisting sleep impairment. In a dose of 3 mg and above, melatonin improves climacteric symptoms in one or more domains. The vast majority of the studies had a low risk for bias. In light of multiple health benefits and an excellent safety profile, melatonin administration should be considered in menopausal women.
Topics: Bone Density; Female; Humans; Melatonin; Menopause; Sleep
PubMed: 33969545
DOI: 10.1111/jpi.12743 -
Inflammopharmacology Oct 2023Melatonin is a neurohormone secreted predominantly by the pineal gland that is demonstrated to be associated with the pathogenesis of multiple sclerosis (MS). This... (Review)
Review
BACKGROUND
Melatonin is a neurohormone secreted predominantly by the pineal gland that is demonstrated to be associated with the pathogenesis of multiple sclerosis (MS). This research desires to evaluate the tolerability and beneficial effects of exogenous melatonin supplementations in patients with MS.
METHODS
This study was executed following the PRISMA 2020 statement. Both observational and interventional studies which reported the clinical effectiveness and/or safety of melatonin supplementation in patients with MS were included in this systematic review. Ovid, PubMed, Scopus, Embase, and Web of Science databases were searched and the risk of bias in included studies was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools based on study design.
RESULTS
Out of 1304 results of database searches, finally, 14 articles, including 7 randomized controlled trials (RCTs), 6 case-control studies, and one quasi-experimental study, were included based on the full-text review. Included phenotypes of MS were mostly relapsing-remitting MS (RRMS) (in 11 studies); it was secondary progressive MS (SPMS) in only one study, and two other studies had a mixture of the different phenotypes. The course of treatment with melatonin supplementation was between 2 weeks and 12 months. There were no substantial safety issues. Although melatonin was associated with enhanced oxidative stress and inflammation status, concerning the clinical benefits, limited studies suggested improvements in sleep conditions, cognitive outcomes, and fatigue in MS.
DISCUSSION
There are insufficient data to support the regular melatonin prescription in MS. Limitations such as the small number of included studies, the diversity of the dosage, route, and duration of melatonin administration, and the diversity of assessment tests lead to unconvincing findings in this study. There is a need for future studies to achieve a comprehensive judgment on this subject.
Topics: Humans; Melatonin; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Treatment Outcome; Dietary Supplements
PubMed: 37429996
DOI: 10.1007/s10787-023-01271-4 -
Progress in Neuro-psychopharmacology &... Apr 2023Melatonin is a potential therapeutic intervention for improving sleep quality in people with autistic spectrum disorder (ASD). We investigate the effect of using... (Meta-Analysis)
Meta-Analysis Review
Melatonin is a potential therapeutic intervention for improving sleep quality in people with autistic spectrum disorder (ASD). We investigate the effect of using melatonin as a sleep disorder treatment in people with ASD. Interventionist studies were searched in seven databases. A total of 595 references were identified, 15 of which were eligible for the systemic review and meta-analysis. Melatonin use presented a positive effect on total sleep time (standardized mean difference- SMD = 0.78; 95%CI = 0.35; 1.21; I = 91%), on sleep latency (SMD = 1.23; 95%CI = 0.35; 2.11; I = 94%), and on sleep efficiency (SMD = -0.70; 95%CI = -1.23; -0.16; I = 91%) when comparing the intervention group with the placebo/control group via the global analysis. According to the global analysis, the wake after sleep onset and night awakening parameters were not statistically significant. Melatonin has possible efficacy over total time, latency, and efficiency sleep parameters.
Topics: Humans; Melatonin; Autistic Disorder; Sleep; Polysomnography; Autism Spectrum Disorder; Sleep Wake Disorders
PubMed: 36584862
DOI: 10.1016/j.pnpbp.2022.110695 -
International Immunopharmacology Jul 2023Melatonin is a hormone synthesized by the pineal gland, and has antioxidative effects in reducing acute kidney injury (AKI). In the past three years, an increasing... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Melatonin is a hormone synthesized by the pineal gland, and has antioxidative effects in reducing acute kidney injury (AKI). In the past three years, an increasing number of studies have evaluated whether melatonin has a protective effect on AKI. The study systematically reviewed and assessed the efficacy and safety of melatonin in preventing AKI.
MATERIAL AND METHODS
A systematic literature search was conducted in the PubMed, Embase, and Web of Science databases on February 15, 2023. Eligible records were screened according to the inclusion and exclusion criteria. The odds ratio and Hedges' gwith the corresponding 95% confidence intervals were selected to evaluate the effects of melatonin on AKI. We pooled extracted data using a fixed- or random-effects model based on a heterogeneity test.
RESULTS
There were five studies (one cohort study and four randomized controlled trials) included in the meta-analysis. Although the glomerular filtration rate (GFR) may be significantly improved by melatonin, the incidence of AKI was not significantly decreased in the melatonin group compared with the control group in randomized controlled trials (RCTs).
CONCLUSIONS
In our study, the present results do not support a direct effect of melatonin use on the reduction of AKI. More well-designed clinical studies with larger sample size are required in the future.
Topics: Humans; Melatonin; Acute Kidney Injury
PubMed: 37279642
DOI: 10.1016/j.intimp.2023.110372 -
Nutrition (Burbank, Los Angeles County,... 2021According to in vivo and in vitro studies, melatonin appears to be a potential supplement for obesity reduction. The aim of this study was to review the literature on... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
According to in vivo and in vitro studies, melatonin appears to be a potential supplement for obesity reduction. The aim of this study was to review the literature on randomized clinical trials that evaluated the effects of melatonin supplementation on anthropometric indicators of obesity in humans.
METHODS
We conducted a systematic review with meta-analysis in the following databases: Pubmed, LILACS, Scielo, Scopus, Web of Science, Cochrane, and Embase. We included studies that evaluated melatonin supplementation's effects, compared with placebo, on anthropometric measures, including body weight, body mass index (BMI), and waist circumference, in people ≥18 y of age. This systematic review and meta-analysis were registered on PROSPERO: CRD42021241079.
RESULTS
Of the 23 studies included, 11 showed significant results from melatonin supplementation on weight loss, BMI, or waist circumference, compared with placebo. In the meta-analysis, melatonin supplementation significantly reduced body weight (standardized mean difference, -0.48; 95% confidence interval, -0.94 to -0.02; P = <0.01; I = 92%). Results for BMI and waist circumference were null. The I tests were significant for the analyses with significant results.
CONCLUSION
The results demonstrated that melatonin supplementation was responsible for significantly reducing body weight. More studies are needed before melatonin can be recommended for weight loss.
Topics: Body Mass Index; Body Weight; Dietary Supplements; Humans; Melatonin; Obesity; Randomized Controlled Trials as Topic; Waist Circumference
PubMed: 34626955
DOI: 10.1016/j.nut.2021.111399 -
Journal of Sleep Research Dec 2023Insomnia is a common disorder and cognitive behavioural therapy for insomnia (CBT-I) is recommended as first-line treatment. However, CBT-I is not widely distributed and... (Review)
Review
Insomnia is a common disorder and cognitive behavioural therapy for insomnia (CBT-I) is recommended as first-line treatment. However, CBT-I is not widely distributed and infrequently available while medication is not indicated for long-term use. To close this evident gap in supply, alternative treatments could be utilised. High-quality research on this topic is scarce, and there is currently no comprehensive publication on the effectiveness of alternative treatments. To address this pressing question, we systematically summarised the existing research on alternative treatments for insomnia. A comprehensive search of systematic reviews and (network) meta-analyses of randomised controlled trials investigating the efficacy of alternative treatments compared to waiting-list control or placebo in adults with insomnia disorder with or without comorbidities was conducted in PubMed, MEDLINE, PsycInfo, and PsycArticles on December 6, 2022, yielding 391 records. Finally, 15 eligible studies were included. Evidence on acupuncture, exogenous melatonin, mind-body interventions and exercise, repetitive transcranial magnetic stimulation (rTMS), valerian, and light exposure was found. Acupuncture, rTMS and mind-body exercises significantly improved sleep quality and insomnia severity but effects on objectively assessed outcomes were inconclusive. Melatonin led to a reduction in both self-reported and objectively assessed sleep onset latency. Light exposure and valerian did not significantly improve sleep outcomes. Overall, the quality of studies was rated as low. Results indicate that alternative treatments are effective mostly on subjective outcomes. However, evidence on the efficacy of some intervention types is sparse and there is a need for high-quality original studies. Future research could investigate whether combining different alternative treatment aspects with CBT-I improves individual treatment.
Topics: Adult; Humans; Cognitive Behavioral Therapy; Melatonin; Sleep; Sleep Initiation and Maintenance Disorders; Systematic Reviews as Topic; Meta-Analysis as Topic; Randomized Controlled Trials as Topic
PubMed: 37527850
DOI: 10.1111/jsr.13979