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Frontiers in Endocrinology 2021Abnormal orexin-A levels in cerebrospinal fluid (CSF) have been identified in Alzheimer's disease (AD) and other neurodegenerative diseases. However, few studies have... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Abnormal orexin-A levels in cerebrospinal fluid (CSF) have been identified in Alzheimer's disease (AD) and other neurodegenerative diseases. However, few studies have focused on Lewy body disease (LBD) and often with debatable outcomes. Thus, we performed this systematic review and meta-analysis to investigate orexin-A levels in LBD by incorporating data from different studies.
METHODS
We gathered studies comparing orexin-A levels in patients with LBD and controls (including healthy controls and other dementia subtypes). In the initial search, 117 relevant articles were identified. After a selection process, seven studies, conducted in Japan, USA, Spain, Switzerland, France, Italy, and Netherlands, were chosen.
RESULTS
In total, 179 patients with LBD and 253 controls were included. Patients with LBD had significantly lower mean orexin-A CSF levels when compared with patients with AD [standard mean difference (SMD): -0.35, 95% confidence interval (CI): -0.70 to -0.00, Z = 1.96, P = 0.05], whereas mean orexin-A levels were significantly higher when compared with patients with frontotemporal lobar degeneration (FTLD) (SMD: 0.61, 95% CI: 0.23-0.99, Z = 3.12, P = 0.002). Orexin-A CSF levels in LBD patients were approximately equal to levels in healthy elderly individuals, whereas they were significantly decreased in LBD patients with excessive daytime sleepiness (EDS) (SMD: -0.15, 95% CI: -0.59 to 0.29, Z = 0.67, P = 0.50).
CONCLUSIONS
We showed that orexin-A levels in patients with LBD were not very different from those in normal elderly individuals, whereas they were lower than those in AD patients and higher than those in FTLD patients. The influence of hypersomnia on orexin-A levels should be carefully interpreted.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42021265900.
Topics: Alzheimer Disease; Animals; Humans; Lewy Body Disease; Orexins
PubMed: 34867809
DOI: 10.3389/fendo.2021.765701 -
Frontiers in Pharmacology 2023Systematic comparisons of the doses of the Food and Drug Administration (FDA)-approved dual orexin receptor antagonists (DORAs) for people with insomnia are limited....
Systematic comparisons of the doses of the Food and Drug Administration (FDA)-approved dual orexin receptor antagonists (DORAs) for people with insomnia are limited. PubMed, Embase, Cochrane Library, and Clinicaltrials. gov were systematically searched to identify relevant studies published before 31 October 2022. We assessed the certainty of evidence using the confidence in network meta-analysis (CINeMA) framework. We pooled 7257 participants from 9 randomized controlled trials (RCTs). Moderate to high certainty evidence demonstrated suvorexant (20 and 40 mg) and daridorexant (10 and 50 mg) as the most effective in latency to persistent sleep (LPS) reduction. Lemborexant at 5 and 10 mg was the most effective in subjective sleep onset time (sTSO) reduction. For wake time after sleep onset (WASO), all drugs except daridorexant 5 mg were more effective than placebo. Lemborexant 5 mg was among the best in subjective WASO (sWASO) (moderate to high certainty) and had the highest surface under the curve ranking area (SUCRA) values for sWASO (100%). For total sleep time (TST), suvorexant and daridorexant, except the respective minimum doses, were more effective than placebo, while suvorexant 40 mg and lemborexant 10 mg may have been the most effective for subjective TST (sTST) (low to very low certainty). Suvorexant 40 mg (RR 1.09), suvorexant 80 mg (RR 1.65), and daridorexant 25 mg (RR 1.16) showed a higher safety risk than placebo. Suvorexant 20 mg, lemborexant 5 mg, lemborexant 10 mg, and daridorexant 50 mg represent suitable approaches for insomnia. clinicaltrials.gov, PROSPERO (CRD42022362655).
PubMed: 37261282
DOI: 10.3389/fphar.2023.1175372 -
Frontiers in Psychiatry 2022Recent treatment guidelines for chronic insomnia recommend pharmacological and non-pharmacological therapies. One of the contemporary drug options for insomnia includes...
Dual orexin receptor antagonists for treatment of insomnia: A systematic review and meta-analysis on randomized, double-blind, placebo-controlled trials of suvorexant and lemborexant.
STUDY OBJECTIVES
Recent treatment guidelines for chronic insomnia recommend pharmacological and non-pharmacological therapies. One of the contemporary drug options for insomnia includes dual orexin receptor antagonist (DORA), such as suvorexant and lemborexant. We conducted a systematic review and meta-analysis for the treatment of insomnia with suvorexant and lemborexant based on randomized, double-blind, placebo-controlled Trials.
METHODS
We conducted a comprehensive search on three databases (PubMed/Medline, Web of Science, and Cochrane Library) till August 14, 2021, without any restrictions to retrieve the relevant articles. The effect sizes were computed presenting the pooled mean difference or risk ratio along with 95% confidence interval of each outcome.
RESULTS
Our search showed eight articles (five for suvorexant and three for lemborexant). Results of diary measures, rating scales, polysomnography results, treatment discontinuation, and adverse events were measured. All efficacy outcome measures favorably and significantly differed in the suvorexant compared to placebo. Safety profile did not differ significantly except for somnolence, excessive daytime sleepiness/sedation, fatigue, back pain, dry mouth, and abnormal dreams. Important adverse events including hallucinations, suicidal ideation/behavior and motor vehicle accidents did not differ between suvorexant and placebo. All the efficacy outcomes significantly differed between lemborexant 5 and lemborexant 10 compared to placebo. Somnolence rate for lemborexant 5 and lemborexant 10 and nightmare for lemborexant 10 were significantly higher than placebo.
CONCLUSION
The present meta-analysis reported that suvorexant and lemborexant are efficacious and safe agents for the patients with insomnia. Further data in patients with insomnia and various comorbid conditions are needed.
PubMed: 36578296
DOI: 10.3389/fpsyt.2022.1070522 -
Obesity Reviews : An Official Journal... Nov 2020In the current study, a systematic review and meta-analysis were conducted to summarize and assess whether short sleep duration is associated with appetite-regulating... (Meta-Analysis)
Meta-Analysis Review
In the current study, a systematic review and meta-analysis were conducted to summarize and assess whether short sleep duration is associated with appetite-regulating hormones and adipokine levels. Reference databases were searched for studies related to sleep and appetite-regulating hormones and adipokines. Qualitative and quantitative syntheses were conducted to evaluate the relationship between sleep duration and the level of appetite-regulating hormones and adipokines, including leptin, ghrelin, adiponectin, resistin, and orexin. Twenty-one of 3536 studies, covering a total of 2250 participants, met the inclusion criteria. Leptin, ghrelin, and adiponectin were included in the meta-analysis. Ghrelin levels were higher in the short sleep group (standard mean difference [SMD] = 0.14, 95% CI [0.03, 0.25], p = 0.01). Significant differences between the short sleep group and recommended sleep group were also noted in leptin level experimental subgroup studies (SMD = 0.19, 95% CI [0.03, 0.35], p = 0.02) and ghrelin level cross-sectional subgroup studies (SMD = 0.14, 95% CI [0.02, 0.27], p = 0.03). A rise in leptin and ghrelin levels were also observed in sleep deprivation groups (SMD = 0.24, 95% CI [0.10, 0.39], p = 0.001 and SMD = 0.18, 95% CI [0.04, 0.33], p = 0.01, respectively). In conclusion, short sleep duration is associated with an increased ghrelin level, while sleep deprivation had a significant effect on the levels of both leptin and ghrelin.
Topics: Adipokines; Appetite; Cross-Sectional Studies; Humans; Sleep; Time Factors
PubMed: 32537891
DOI: 10.1111/obr.13051 -
Expert Opinion on Drug Safety 2023Insomnia is a multi-factorial disorder with conventional treatment options that are not satisfactory for many patients. This metaanalysis analyzed the safety and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Insomnia is a multi-factorial disorder with conventional treatment options that are not satisfactory for many patients. This metaanalysis analyzed the safety and efficacy of daridorexant.
METHODS
An electronic database search for RCTs was conducted on Medline via PubMed, Cochrane, and Clinicaltrials.gov using the terms 'Daridorexant,' 'RCT,' 'Insomnia' trials evaluating the efficacy and/or safety of daridorexant for insomnia were included. The data were synthesized using Cochrane review manager version 5.4.1. Cochrane risk of bias 2.0 tool and GRADEpro-GDT were used to assess the methodological and evidence quality, respectively.
RESULTS
Of 109 searched studies, four trials were included. The risk of treatment-emergent adverse events with 25 mg daridorexant [risk ratio (RR) = 1.12 (0.88, 1.43), = 0.36; I = 0%] and 50 mg daridorexant [RR = 1.25 (0.88, 1.79), = 0.22; I = 28%] and serious adverse events with 25 mg [RR = 0.86 (0.23, 3.19), = 0.82, I = 56%] and 50 mg [RR = 1.32 (0.29, 6.08), = 0.72, I = 52%] was comparable to placebo [Moderate quality evidence]. Risk of nasopharyngitis was also comparable to placebo. The efficacy parameters like wake after sleep onset, latency to persistent sleep, and subjective total sleep time showed significant improvement with daridorexant. The risk of bias is low for three studies and some concern for one.
CONCLUSION
Daridorexant is a safer and efficacious agent for induction and maintenance of sleep for chronic insomnia.
PROSPERO
The registration number is CRD42022335233.
CLINICAL TRIAL REGISTRATION
www.clinicaltrials.gov identifiers are NCT03575104, NCT03545191, NCT03679884, and NCT02839200).
Topics: Humans; Sleep Initiation and Maintenance Disorders; Imidazoles; Pyrrolidines
PubMed: 37526060
DOI: 10.1080/14740338.2023.2243217 -
Sleep Medicine: X Dec 2023Insomnia is a common disease, and the application of various types of sleeping pills for cognitive impairment is controversial, especially as different doses can lead to... (Review)
Review
BACKGROUND
Insomnia is a common disease, and the application of various types of sleeping pills for cognitive impairment is controversial, especially as different doses can lead to different effects. Therefore, it is necessary to evaluate the cognitive impairment caused by different sleeping pills to provide a theoretical basis for guiding clinicians in the selection of medication regimens.
OBJECTIVE
To evaluate whether various different doses (low, medium and high) of anti-insomnia drugs, such as the dual-orexin receptor antagonist (DORA), zopiclone, eszopiclone and zolpidem, induce cognitive impairment.
METHODS
The PubMed, Embase, Scopus, Cochrane Library, and Google Scholar databases were searched from inception to September 20th, 2022 for keywords in randomized controlled trials (RCTs) to evaluate the therapeutic effects of DORA, eszopiclone, zopiclone and zolpidem on sleep and cognitive function. The primary outcomes were indicators related to cognitive characteristics, including scores on the Digit Symbol Substitution Test (DSST) and daytime alertness. The secondary outcomes were the indicators associated with sleep and adverse events. Continuous variables were expressed as the standard mean difference (SMD). Data were obtained through GetData 2.26 and analyzed by Stata v.15.0.
RESULTS
A total of 8702 subjects were included in 29 studies. Eszopiclone significantly increased the daytime alertness score (SMD = 3.00, 95 % CI: 1.86 to 4.13) compared with the placebo, and eszopiclone significantly increased the daytime alertness score (SMD = 4.21, 95 % CI: 1.65 to 6.77; SMD = 3.95, 95 % CI: 1.38 to 6.51; SMD = 3.26, 95 % CI: 0.38 to 6.15; and SMD = 3.23, 95 % CI: 0.34 to 6.11) compared with zolpidem, zolpidem, DORA, and eszopiclone, respectively. Compared with the placebo, zopiclone, zolpidem, and eszopiclone, DORA significantly increased the TST (SMD = 2.39, 95 % CI: 1.11 to 3.67; SMD = 6.00, 95 % CI: 2.73 to 9.27; SMD = 1.89, 95 % CI: 0.90 to 2.88; and SMD = 1.70, 95 % CI: 0.42 to 2.99, respectively).
CONCLUSION
We recommend DORA as the best intervention for insomnia because it was highly effective in inducing and maintaining sleep without impairing cognition. Although zolpidem had a more pronounced effect on sleep maintenance, this drug is better for short-term use. Eszopiclone and zopiclone improved sleep, but their cognitive effects have yet to be verified.
PubMed: 38149178
DOI: 10.1016/j.sleepx.2023.100094 -
Sleep Feb 2024Dual orexin receptor antagonists (DORAs) are emerging treatments for insomnia. This meta-analysis study aimed to assess the safety of FDA-approved DORAs (suvorexant,... (Meta-Analysis)
Meta-Analysis
STUDY OBJECTIVES
Dual orexin receptor antagonists (DORAs) are emerging treatments for insomnia. This meta-analysis study aimed to assess the safety of FDA-approved DORAs (suvorexant, lemborexant, and daridorexant), focusing on narcolepsy-like symptoms associated with these drugs.
METHODS
Five prominent databases were searched to identify randomized controlled trials (RCTs) on this topic. Primary safety outcomes included treatment-emergent adverse events (TEAEs), treatment-related TEAEs, TEAEs leading to discontinuation, and serious TEAEs. Excessive daytime sleepiness (EDS), sleep paralysis, and hallucinations were categorized as adverse events (AEs)-related narcolepsy-like symptoms.
RESULTS
Eleven RCTs with 7703 patients were included. DORAs were associated with a higher risk of TEAEs (risk ratio [RR], 1.09; 95% confidence interval [CI], 1.03 to 1.15) and treatment-related TEAEs (RR, 1.69; 95% CI: 1.49 to 1.92) when compared to placebo. The DORA group exhibited a significantly higher risk of EDS (RR, 2.15; 95% CI: 1.02 to 4.52) and sleep paralysis (RR, 3.40; 95% CI: 1.18 to 9.80) compared to the placebo group.
CONCLUSION
This meta-analysis achieved a comparative evaluation of the clinical safety and tolerability of FDA-approved DORAs for primary insomnia, specifically focusing on AEs-related narcolepsy-like symptoms. This study contributes to understanding the safety profile of FDA-approved DORAs for treating insomnia.
Topics: Humans; Sleep Initiation and Maintenance Disorders; Orexin Receptor Antagonists; Sleep Paralysis; Narcolepsy
PubMed: 37950346
DOI: 10.1093/sleep/zsad293 -
Expert Review of Neurotherapeutics May 2024This systematic review and meta-analysis evaluates the evidence from randomized controlled trials (RCTs) involving pharmacological interventions for improving sleep in... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
This systematic review and meta-analysis evaluates the evidence from randomized controlled trials (RCTs) involving pharmacological interventions for improving sleep in people with Alzheimer's disease (AD).
METHODS
A systematic literature search in eight databases from January 2000 to July 2023 focusing on RCTs that compared a pharmacological intervention with a placebo for enhancing sleep in people with AD. The authors registered the study protocol at Prospero, followed the PRISMA guidelines, and produced the pooled estimates using random-effect or IVhet models.
RESULTS
Eight different interventions and 29 different sleep outcomes were examined in 14 RCTs included in this review. Eszopiclone positively affected sleep efficiency, as did orexin antagonists. However, there was no difference when melatonin was used. The interventions demonstrated low discontinuation rates and a few adverse drug reactions.
CONCLUSION
Although melatonin was the most investigated intervention, the evidence for its efficacy is inconclusive. On the other hand, trazodone and orexin receptor antagonists showed promising results; however, more RCTs are needed for definite answers.
Topics: Humans; Alzheimer Disease; Melatonin; Randomized Controlled Trials as Topic; Sleep; Trazodone
PubMed: 38597219
DOI: 10.1080/14737175.2024.2341004 -
Life (Basel, Switzerland) Jan 2023Background and objective: Obstructive sleep apnea (OSA) can be related to changes in the levels of adipokines and neuropeptides, which in turn may affect the energy... (Review)
Review
Background and objective: Obstructive sleep apnea (OSA) can be related to changes in the levels of adipokines and neuropeptides, which in turn may affect the energy balance components of neuronal cells. Herein, a systematic review and meta-analysis checked the changes in serum/plasma levels of omentin-1 (OM-1: an adipokine) and orexin-A (OXA: a neuropeptide) in adults (age > 18 years old) with OSA (aOSA) compared to controls. Materials and methods: Four databases (Cochrane Library, PubMed, Web of Science, and Scopus) were systematically searched until 14 November 2022, without any restrictions. The Joanna Briggs Institute (JBI) critical appraisal checklist adapted for case−control studies was used to assess the quality of the papers. The effect sizes were extracted using the Review Manager 5.3 software for the blood levels of OM-1 and OXA in aOSA compared with controls. Results: Thirteen articles, with six studies for OM-1 levels and eight for OXA levels, were included. The pooled standardized mean differences were −0.85 (95% confidence interval (CI): −2.19, 0.48; p = 0.21; I2 = 98%) and −0.20 (95%CI: −1.16, 0.76; p = 0.68; I2 = 96%) for OM-1 and OXA levels, respectively. Among the studies reporting OM-1, five were high and one was moderate quality. Among the studies reporting OXA, six were moderate, one was high, and one was low quality. Based on the trial sequential analysis, more participants are needed to confirm the pooled results of the analyses of blood levels of OM-1 and OXA. In addition, the radial plot showed outliers as significant factors for high heterogeneity. Conclusions: The main findings indicated a lack of association between the blood levels of OM-1 and OXA and OSA risk. Therefore, OM-1 and OXA did not appear to be suitable biomarkers for the diagnosis and development of OSA.
PubMed: 36676194
DOI: 10.3390/life13010245 -
Sleep Medicine May 2021Narcolepsy, a sleep disorder characterized by loss of hypocretin neurons, has been associated with metabolic disturbances. Although the metabolic alterations in... (Meta-Analysis)
Meta-Analysis Review
Narcolepsy, a sleep disorder characterized by loss of hypocretin neurons, has been associated with metabolic disturbances. Although the metabolic alterations in narcolepsy patients are widely investigated in the literature, the results are controversial. We performed a systematic search of literature to identify metabolic profiling studies in narcolepsy patients. A total of 48 studies were included in the meta-analysis. Narcolepsy patients exhibited higher prevalence of obesity (log OR = 0.93 [0.73-1.13], P < 0.001), diabetes mellitus (log OR = 0.64 [0.34, 0.94], P < 0.001), hypertension (log OR = 0.33 [0.11, 0.55], P < 0.001), and dyslipidemia (log OR = 1.19 [0.60, 1.77], P < 0.001) compared with non-narcoleptic controls. Narcolepsy was associated with higher BMI (SMD = 0.50 [0.32-0.68], P < 0.001), waist circumference (MD = 8.61 [2.03-15.19], P = 0.01), and plasma insulin (SMD = 0.61 [0.14-1.09], P = 0.01). Levels of fasting blood glucose (SMD = -0.25 [-0.61,0.10], P = 0.15), BMR-RMR (SMD = -0.17 [-0.52-0.18], P = 0.34), systolic blood pressure (SMD = 0.29 [-0.39-0.97], P = 0.40), diastolic blood pressure (SMD = 0.39 [-0.62, 1.40], P = 0.45), CSF melanin-concentrating hormone (MD = 5.56 [-30.79-41.91], P = 0.76), serum growth hormone (SMD = 7.84 [-7.90-23.57], P = 0.33), as well as plasma and CSF leptin (SMD = 0.10 [-1.32-1.51], P = 0.89 and MD = 0.01 [-0.02-0.04], P = 0.56, respectively) did not significantly differ between narcolepsy patients and controls. These findings necessitate early screening of metabolic alterations and cardiovascular risk factors in narcolepsy patients to reduce the morbidity and mortality rates.
Topics: Humans; Leptin; Metabolome; Narcolepsy; Obesity; Orexins; Sleep Wake Disorders
PubMed: 33740593
DOI: 10.1016/j.sleep.2021.02.040