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Sleep Medicine Reviews Apr 2023Insomnia is one of the most common and burdensome disorders in adults. We compared and ranked insomnia medication on the basis of their efficacy and tolerability. We... (Meta-Analysis)
Meta-Analysis Review
Insomnia is one of the most common and burdensome disorders in adults. We compared and ranked insomnia medication on the basis of their efficacy and tolerability. We performed a systematic review and network meta-analysis of placebo-controlled or head-to-head randomized controlled trials for primary insomnia in adults comparing 20 drugs. We searched eight databases and seven trial registers from inception to March 1st, 2022. Primary outcomes included sleep latency (SL), awake time after sleep onset (WASO) and discontinuation for adverse events (AED), and secondary outcomes included total sleep time (TST), sleep efficiency (SE), sleep quality (SQ) and adverse events (ADE). Pooled standardized mean differences or odds ratios with 95% credible intervals were estimated using pairwise and network meta-analysis with random-effects. Differences among trial findings were explored in subgroup and sensitivity analyses. Confidence in evidence was assessed using GRADE. The PROSPERO registered number is CRD42020182144. We identified 22,538 records and included 69 studies (17,319 patients). Orexin receptor antagonists (ORAs) are more efficacious than benzodiazepine-like drugs (Z-drugs) and placebo for WASO and SE, and better than melatonin receptor agonists (MRAs) for SL, WASO and SE. ORAs ranked the best in SL (SUCRA value: 0.84), WASO (0.93), TST (0.86) and SE (0.96). Lemborexant and daridorexant (two ORAs) showed greater efficacy than placebo for SL, WASO, and TST, with good tolerability. Z-drugs were more efficacious than placebo for SL, WASO, TST and SE, but with higher risk to safety. Zaleplon and eszopiclone had better efficacy than placebo for TST and SQ respectively. MRAs may also be efficacious for sleep-onset insomnia with good safety. However, the long-term adverse effects of all medications are unclear. Insomnia medications differ in their efficacy and tolerability. ORAs have superior efficacy and tolerability. These findings should aid clinicians in matching risk/benefits of drugs available in their countries to insomnia symptoms.
Topics: Humans; Adult; Sleep Initiation and Maintenance Disorders; Network Meta-Analysis; Sleep; Hypnotics and Sedatives; Wakefulness; Treatment Outcome
PubMed: 36701954
DOI: 10.1016/j.smrv.2023.101746 -
Sleep Medicine Reviews Feb 2022Current theories of the glymphatic system (GS) hypothesize that it relies on cerebrospinal fluid (CSF) circulation to disseminate growth factors and remove metabolic... (Review)
Review
Current theories of the glymphatic system (GS) hypothesize that it relies on cerebrospinal fluid (CSF) circulation to disseminate growth factors and remove metabolic waste from the brain with increased CSF production and circulation during sleep; thereby, linking sleep disturbance with elements of CSF circulation and GS exchange. However, our growing knowledge of the relations between sleep, CSF, and the GS are plagued by variability in sleep and CSF measures across a wide array of pathologies. Hence, this review aims to summarize the dynamic relationships between sleep, CSF-, and GS-related features in samples of typically developing individuals and those with autoimmune/inflammatory, neurodegenerative, neurodevelopmental, sleep-related, neurotraumatic, neuropsychiatric, and skull atypicalities. One hundred and ninety articles (total n = 19,129 participants) were identified and reviewed for pathology, CSF circulation and related metrics, GS function, and sleep. Numerous associations were documented between sleep problems and CSF metabolite concentrations (e.g., amyloid-beta, orexin, tau proteins) and increased CSF volumes or pressure. However, these relations were not universal, with marked differences across pathologies. It is clear that elements of CSF circulation/composition and GS exchange represent pathways influenced by sleep; however, carefully designed studies and advances in GS measurement are needed to delineate the nuanced relationships.
Topics: Amyloid beta-Peptides; Brain; Glymphatic System; Humans; Sleep; Sleep Wake Disorders
PubMed: 34902819
DOI: 10.1016/j.smrv.2021.101572 -
Sleep Medicine Reviews Feb 2022The efficacy and safety of dual orexin receptor antagonists (DORAs) for primary insomnia have been well verified in several large randomized controlled trials (RCTs)... (Meta-Analysis)
Meta-Analysis Review
The efficacy and safety of dual orexin receptor antagonists (DORAs) for primary insomnia have been well verified in several large randomized controlled trials (RCTs) over the past several decades. However, there have been few systematic comparisons of different DORAs, and the best DORA for insomniacs has remained unclear. Here, Medline, Embase, Cochrane library, and clinicaltrials.gov were searched for RCTs (through December 31, 2020) to evaluate different DORAs versus a placebo. We pooled data from 13 RCTs. DORAs were superior to the placebo in all efficacy outcomes except the subjective number of awakenings (P = 0.90), but also showed higher risks of somnolence, abnormal dreams, fatigue, and dry mouth (somnolence: P < 0.00001; abnormal dreams: P = 0.03; fatigue: P = 0.001; dry mouth: P = 0.007). No statistical differences were found between any two of the DORAs in terms of primary efficacy outcomes. However, lemborexant yielded the three-highest surfaces under the curve ranking area (SUCRA) values (78.25%, 96.25% and 89.13%). Taken together, we conclude that DORAs are superior to the placebo in terms of efficacy and safety measures.
Topics: Humans; Network Meta-Analysis; Orexin Receptor Antagonists; Sleep Initiation and Maintenance Disorders; Wakefulness
PubMed: 34902823
DOI: 10.1016/j.smrv.2021.101573 -
Drugs May 2023Pharmacological treatment is common in practice and widely used for the management of insomnia. However, evidence comparing the relative effectiveness, safety, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pharmacological treatment is common in practice and widely used for the management of insomnia. However, evidence comparing the relative effectiveness, safety, and certainty of evidence among drug classes and individual drugs for insomnia are still lacking. This study aimed to determine the relative effectiveness, safety, and tolerability of drugs for insomnia.
METHODS
In this systematic review and network meta-analysis we systematically searched PubMed, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and ClinicalTrials.gov, from inception to January 10, 2022 to identify randomized controlled trials that compared insomnia drugs with placebo or an active comparator in adults with insomnia. We conducted random-effects frequentist network meta-analyses to summarize the evidence, and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty, categorize interventionsand present the findings.
RESULTS
A total of 148 articles met our eligibility criteria; these included 153 trials which enrolled 46,412 participants and assessed 36 individual drugs from eight drug classes. Compared with placebo, both subjectively and objectively measured total sleep time were significantly improved with non-benzodiazepine (subjective: mean difference [MD] 25.07, 95% confidence interval [CI] 15.49-34.64, low certainty; objective: MD 22.34, 95% CI 7.64-37.05, high certainty), antidepressants (subjective: MD 54.40, 95% CI 34.96-75.83, low certainty; objective: MD 35.64, 95% CI 13.05-58.24, high certainty), and orexin receptor antagonists (subjective: MD 21.62, 95% CI 0.84-42.40, high certainty; objective: MD 31.81, 95% CI 2.66-60.95, high certainty); of which doxepin, almorexant, suvorexant, and lemborexant were among the relatively effective drugs with relatively good tolerability and lower risks of any adverse events (AEs). Both subjectively and objectively measured sleep onset latency were significantly shortened with non-benzodiazepines (subjective: MD - 10.12, 95% CI - 13.84 to - 6.40, moderate certainty; objective: MD - 12.11, 95% CI - 19.31 to - 4.90, moderate certainty) and melatonin receptor agonists (subjective: MD - 7.73, 95% CI - 15.21 to - 0.26, high certainty; objective: MD - 7.04, 95% CI - 12.12 to - 1.95, moderate certainty); in particular, zopiclone was among the most effective drugs with a lower risk of any AEs but worse tolerability. Non-benzodiazepines could significantly decrease both subjective and objective measured wake time after sleep onset (subjective: MD - 16.67, 95% CI - 21.79 to - 11.56, moderate certainty; objective: MD - 13.92, 95% CI - 22.71 to - 5.14, moderate certainty).
CONCLUSIONS
Non-benzodiazepines probably improve total sleep time, sleep onset latency, and wake time after sleep onset. Other insomnia drug classes and individual drugs also showed potential benefits in improving insomnia symptoms. However, the choice of insomnia drugs should be based on the phenotype of insomnia presented, as well as each drug's safety and tolerability. Protocol registration PROSPERO (CRD42019138790).
Topics: Humans; Sleep Initiation and Maintenance Disorders; Network Meta-Analysis; Randomized Controlled Trials as Topic; Antidepressive Agents; Sleep
PubMed: 36947394
DOI: 10.1007/s40265-023-01859-8 -
Frontiers in Psychiatry 2022Orexins are polypeptides regulating appetite, sleep-wake cycle, and cognition functions, which are commonly disrupted in patients with schizophrenia. Patients with...
BACKGROUND
Orexins are polypeptides regulating appetite, sleep-wake cycle, and cognition functions, which are commonly disrupted in patients with schizophrenia. Patients with schizophrenia show a decreased connectivity between the prefrontal cortex and midline-anterior thalamus, and orexin can directly activate the axon terminal of cells within the prefrontal cortex and selectively depolarize neurons in the midline intralaminar nuclei of the thalamus. To address the relationship between orexin and schizophrenia, this study performed a meta-analysis on the alteration of plasma orexin-A levels in patients with schizophrenia.
METHOD
We searched eligible studies in PubMed, Embase, Cochrane, and China National Knowledge Infrastructure (CNKI) from 1998 to September 3, 2021. A total of 8 case-control studies were included in the meta-analyses, providing data on 597 patients with schizophrenia and 370 healthy controls. The Stata version 16.0 software was used to calculate the Hedges's adjusted g with 95% confidence intervals (CI).
RESULTS
The plasma orexin-A levels were not altered in subjects with schizophrenia ( = 597) when compared to healthy controls ( = 370). Subgroup analyses of gender (male and female vs. only male), country (China vs. other countries), medication (medication vs. non-medication), and the measurement of plasma orexin-A (Enzyme-linked immunosorbent assay vs. radioimmunoassay) revealed heterogeneity ranging from 30.15 to 98.15%, but none showed a significant alteration of plasma orexin-A levels in patients with schizophrenia. Heterogeneity was lower in the other countries and radioimmunoassay subgroup, while other subgroups remained to be highly heterogeneous. No significant evidence of publication bias was found either in Begg's test or the Egger's test.
CONCLUSION
The present meta-analysis indicated that patients with schizophrenia did not show abnormal plasma levels of orexin-A.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021283455, identifier: CRD42021283455.
PubMed: 35693955
DOI: 10.3389/fpsyt.2022.879414 -
The Cochrane Database of Systematic... Nov 2020Sleep disturbances, including reduced nocturnal sleep time, sleep fragmentation, nocturnal wandering, and daytime sleepiness are common clinical problems in dementia,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sleep disturbances, including reduced nocturnal sleep time, sleep fragmentation, nocturnal wandering, and daytime sleepiness are common clinical problems in dementia, and are associated with significant carer distress, increased healthcare costs, and institutionalisation. Although non-drug interventions are recommended as the first-line approach to managing these problems, drug treatment is often sought and used. However, there is significant uncertainty about the efficacy and adverse effects of the various hypnotic drugs in this clinically vulnerable population.
OBJECTIVES
To assess the effects, including common adverse effects, of any drug treatment versus placebo for sleep disorders in people with dementia.
SEARCH METHODS
We searched ALOIS (www.medicine.ox.ac.uk/alois), the Cochrane Dementia and Cognitive Improvement Group's Specialized Register, on 19 February 2020, using the terms: sleep, insomnia, circadian, hypersomnia, parasomnia, somnolence, rest-activity, and sundowning.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that compared a drug with placebo, and that had the primary aim of improving sleep in people with dementia who had an identified sleep disturbance at baseline.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data on study design, risk of bias, and results. We used the mean difference (MD) or risk ratio (RR) with 95% confidence intervals (CI) as the measures of treatment effect, and where possible, synthesised results using a fixed-effect model. Key outcomes to be included in our summary tables were chosen with the help of a panel of carers. We used GRADE methods to rate the certainty of the evidence.
MAIN RESULTS
We found nine eligible RCTs investigating: melatonin (5 studies, n = 222, five studies, but only two yielded data on our primary sleep outcomes suitable for meta-analysis), the sedative antidepressant trazodone (1 study, n = 30), the melatonin-receptor agonist ramelteon (1 study, n = 74, no peer-reviewed publication), and the orexin antagonists suvorexant and lemborexant (2 studies, n = 323). Participants in the trazodone study and most participants in the melatonin studies had moderate-to-severe dementia due to Alzheimer's disease (AD); those in the ramelteon study and the orexin antagonist studies had mild-to-moderate AD. Participants had a variety of common sleep problems at baseline. Primary sleep outcomes were measured using actigraphy or polysomnography. In one study, melatonin treatment was combined with light therapy. Only four studies systematically assessed adverse effects. Overall, we considered the studies to be at low or unclear risk of bias. We found low-certainty evidence that melatonin doses up to 10 mg may have little or no effect on any major sleep outcome over eight to 10 weeks in people with AD and sleep disturbances. We could synthesise data for two of our primary sleep outcomes: total nocturnal sleep time (TNST) (MD 10.68 minutes, 95% CI -16.22 to 37.59; 2 studies, n = 184), and the ratio of day-time to night-time sleep (MD -0.13, 95% CI -0.29 to 0.03; 2 studies; n = 184). From single studies, we found no evidence of an effect of melatonin on sleep efficiency, time awake after sleep onset, number of night-time awakenings, or mean duration of sleep bouts. There were no serious adverse effects of melatonin reported. We found low-certainty evidence that trazodone 50 mg for two weeks may improve TNST (MD 42.46 minutes, 95% CI 0.9 to 84.0; 1 study, n = 30), and sleep efficiency (MD 8.53%, 95% CI 1.9 to 15.1; 1 study, n = 30) in people with moderate-to-severe AD. The effect on time awake after sleep onset was uncertain due to very serious imprecision (MD -20.41 minutes, 95% CI -60.4 to 19.6; 1 study, n = 30). There may be little or no effect on number of night-time awakenings (MD -3.71, 95% CI -8.2 to 0.8; 1 study, n = 30) or time asleep in the day (MD 5.12 minutes, 95% CI -28.2 to 38.4). There were no serious adverse effects of trazodone reported. The small (n = 74), phase 2 trial investigating ramelteon 8 mg was reported only in summary form on the sponsor's website. We considered the certainty of the evidence to be low. There was no evidence of any important effect of ramelteon on any nocturnal sleep outcomes. There were no serious adverse effects. We found moderate-certainty evidence that an orexin antagonist taken for four weeks by people with mild-to-moderate AD probably increases TNST (MD 28.2 minutes, 95% CI 11.1 to 45.3; 1 study, n = 274) and decreases time awake after sleep onset (MD -15.7 minutes, 95% CI -28.1 to -3.3: 1 study, n = 274) but has little or no effect on number of awakenings (MD 0.0, 95% CI -0.5 to 0.5; 1 study, n = 274). It may be associated with a small increase in sleep efficiency (MD 4.26%, 95% CI 1.26 to 7.26; 2 studies, n = 312), has no clear effect on sleep latency (MD -12.1 minutes, 95% CI -25.9 to 1.7; 1 study, n = 274), and may have little or no effect on the mean duration of sleep bouts (MD -2.42 minutes, 95% CI -5.53 to 0.7; 1 study, n = 38). Adverse events were probably no more common among participants taking orexin antagonists than those taking placebo (RR 1.29, 95% CI 0.83 to 1.99; 2 studies, n = 323).
AUTHORS' CONCLUSIONS
We discovered a distinct lack of evidence to guide decisions about drug treatment of sleep problems in dementia. In particular, we found no RCTs of many widely prescribed drugs, including the benzodiazepine and non-benzodiazepine hypnotics, although there is considerable uncertainty about the balance of benefits and risks for these common treatments. We found no evidence for beneficial effects of melatonin (up to 10 mg) or a melatonin receptor agonist. There was evidence of some beneficial effects on sleep outcomes from trazodone and orexin antagonists and no evidence of harmful effects in these small trials, although larger trials in a broader range of participants are needed to allow more definitive conclusions to be reached. Systematic assessment of adverse effects in future trials is essential.
Topics: Alzheimer Disease; Azepines; Caregiver Burden; Cognition; Humans; Indenes; Melatonin; Pyridines; Pyrimidines; Randomized Controlled Trials as Topic; Sleep; Sleep Wake Disorders; Time Factors; Trazodone; Triazoles
PubMed: 33189083
DOI: 10.1002/14651858.CD009178.pub4 -
Arquivos de Neuro-psiquiatria May 2023Several randomized clinical trials (RCTs) have shown that dual orexin receptor antagonists (DORAs) are effective in the treatment of chronic insomnia. However, the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several randomized clinical trials (RCTs) have shown that dual orexin receptor antagonists (DORAs) are effective in the treatment of chronic insomnia. However, the superiority of one particular DORA over the others remains unclear.
OBJECTIVE
To perform a network meta-analysis to evaluate the efficacy of different DORAs in patients with chronic insomnia.
METHODS
The Medline, Embase, and Cochrane Central databases were searched for RCTs that compared DORA with placebo in patients ≥ 18 years of age with a diagnosis of insomnia disorder. We pooled outcomes for wake time after sleep onset (WASO), latency to persistent sleep (LPS), total sleep time (TST), and adverse events (AEs).
RESULTS
We included 10 RCTs with 7,806 patients, 4,849 of whom received DORAs as the intervention. Overall, we found that DORAs were associated with the improvement of all analyzed efficacy outcomes. Concerning TST, an apparent dose-dependent pattern was noticed, with higher doses relating to a longer TST. Lemborexant 10mg provided the largest reduction in WASO (at month 1) in minutes (standardized mean difference [SMD] = -25.40; 95% confidence interval [95%CI] = -40.02--10.78), followed by suvorexant 20/15mg (SMD = -25.29; 95%CI = -36.42--14.15), which also appeared to provide the largest decrease in long-term WASO (SMD = -23.70; 95%CI = -35.89--11.51). The most frequent AEs were somnolence, nasopharyngitis, and headache, with rates of up to 14.8%.
CONCLUSION
Our results suggest that DORAs are associated with greater efficacy when compared with placebo in the treatment of insomnia, a complex 24-hour sleep disorder. Additionally, dosing might play an important role in the management of chronic insomnia.
Topics: Humans; Sleep Initiation and Maintenance Disorders; Orexin Receptor Antagonists; Network Meta-Analysis; Sleep; Wakefulness
PubMed: 37257468
DOI: 10.1055/s-0043-1768667 -
Journal of Managed Care & Specialty... Sep 2021Insomnia is a common disorder associated with a substantial burden of illness, particularly in older adults. To compare the efficacy and safety of lemborexant with... (Comparative Study)
Comparative Study Meta-Analysis
Insomnia is a common disorder associated with a substantial burden of illness, particularly in older adults. To compare the efficacy and safety of lemborexant with specified other insomnia treatments through a systematic literature review and network meta-analysis (NMA). Medline and Embase were systematically searched from inception to February 2019 and updated with a targeted search of PubMed for pivotal trials in March 2021. Randomized controlled trials in adults with primary insomnia were included if they reported results following at least 1 week of treatment. Interventions of interest were specified as lemborexant, suvorexant, benzodiazepines, benzodiazepine receptor agonists (also called Z-drugs [zolpidem, eszopiclone, zaleplon, zopiclone]), trazodone, and ramelteon. Efficacy outcomes included wake after sleep onset (WASO), sleep efficiency (SE), latency to persistent sleep (LPS)/sleep onset latency (SOL), total sleep time (TST) and Insomnia Severity Index (ISI). Bayesian NMA were performed at predetermined time intervals approximating 4 weeks, 3 months, and 6 months. Safety outcomes included serious adverse events (SAEs), withdrawals due to adverse events (AEs), and specified AEs (dizziness, somnolence, and falls). Subgroup analysis was conducted in the older population. 45 studies were included in the NMA. At 4 weeks, lemborexant had the highest probability of being the best treatment for 3 of the 4 outcomes measured objectively by polysomnography-TST, LPS, and SE-and was ranked second to suvorexant on WASO. Eszopiclone was highly ranked for subjectively measured SOL and ISI at 4 weeks, 3 months, and 6 months. Lemborexant was rated more highly than suvorexant in subjective measures of WASO, TST, and SOL at 4 weeks (the differences were not statistically significant). No statistically significant interactions between treatment effect and older subpopulations were found, indicating that the treatment effect was similar in older and adult populations. The safety profile of lemborexant was broadly similar to the other treatments for SAEs and withdrawals due to AEs. A limitation is the age of some of the included studies (3 were published in 1990 or earlier). A further limitation is the lack of stratification of recommended doses. If the doses used in the study publications do not reflect doses used in clinical practice, this could potentially bias the results. Lemborexant was ranked highest of the treatments studied on 3 out of the 4 objectively measured insomnia efficacy outcomes, with a safety profile broadly similar to other insomnia treatments. This work was funded by Eisai Inc., which was involved with all stages of the study and analysis. McElroy, O'Leary, and Adena are consultants with Datalytics Pty Ltd., which was paid by Eisai Inc. for conducting the literature review and analysis. They were not financially compensated for collaborative efforts on publication-related activities. Campbell, Tahami Monfared, and Meier are employed by Eisai Inc. This study was presented as a poster at AMCP Nexus Virtual, October 20-23, 2020 and at the AGS Virtual Annual Scientific Meeting 2021, May 13-15, 2021.
Topics: Humans; Orexin Receptor Antagonists; Pyridines; Pyrimidines; Sleep Initiation and Maintenance Disorders; Treatment Outcome
PubMed: 34121443
DOI: 10.18553/jmcp.2021.21011 -
Sleep Medicine Sep 2021A growing body of evidence suggests that sleep and Alzheimer's disease (AD) have a bi-directional relationship. Emerging research also suggests that orexin, a key... (Meta-Analysis)
Meta-Analysis
OBJECTIVE/BACKGROUND
A growing body of evidence suggests that sleep and Alzheimer's disease (AD) have a bi-directional relationship. Emerging research also suggests that orexin, a key neurotransmitter involved in sleep-wake regulation, may be altered in persons with AD, however results have not been consistent across prior studies. This investigation was conducted to both evaluate the aggregate literature to minimize the risk of bias and identify potential factors associated with heterogeneity across studies.
METHODS
Systematic review identified relevant investigations that compared cerebrospinal fluid orexin in persons with AD and controls. Meta-analysis (random effects model) compared effect size (Hedge's g) for orexin between AD and controls. Meta-regression was additionally performed for key variables of interest to evaluate potential causes of heterogeneity among studies.
RESULTS
17 studies were identified that met inclusion/exclusion criteria. Evidence of publication bias was not identified. Non-significant increases in orexin were observed in AD relative to controls, with moderate to large heterogeneity among studies (Hedge's g = 0.20, p = 0.136, I = 72.6%). Meta-regression demonstrated both year of publication (β = 0.055, p = 0.020) and effect size for phosphorylated tau in AD versus controls (β = 0.417, p = 0.031) were associated with differences in orexin.
CONCLUSIONS
Results do not support broad differences in orexin in AD compared to controls, however, evolving diagnostic criteria may have affected findings across studies. Future research that examines orexin in AD over the longitudinal course of the disorder and explores potential links between phosphorylated tau and orexin are indicated.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Biomarkers; Humans; Orexins; Sleep; Sleep Wake Disorders; tau Proteins
PubMed: 34364094
DOI: 10.1016/j.sleep.2021.07.007 -
International Journal of Molecular... Apr 2023The sleep-wake cycle is a complex multifactorial process involving several neurotransmitters, including acetylcholine, norepinephrine, serotonin, histamine, dopamine,... (Review)
Review
The sleep-wake cycle is a complex multifactorial process involving several neurotransmitters, including acetylcholine, norepinephrine, serotonin, histamine, dopamine, orexin and GABA, that can be, in turn, regulated by different nutrients involved in their metabolic pathways. Although good sleep quality in children has been proven to be a key factor for optimal cognitive, physical and psychological development, a significant and ever-increasing percentage of the pediatric population suffers from sleep disorders. In children, behavioral interventions along with supplements are recommended as the first line treatment. This systematic review was conducted, according to the PRISMA guidelines, with the purpose of assessing the principal nutrients involved in the pathways of sleep-regulating neurotransmitters in children and adolescents. Our focus was the utilization of over the counter (OTC) products, specifically iron, hydroxytryptophan, theanine and antihistamines in the management of different pediatric sleep disorders with the intention of providing a practical guide for the clinician.
Topics: Adolescent; Humans; Child; Sleep; Sleep Initiation and Maintenance Disorders; Histamine; Histamine Antagonists; Neurotransmitter Agents; Sleep Wake Disorders
PubMed: 37175525
DOI: 10.3390/ijms24097821