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Neurological Sciences : Official... May 2023Insomnia is a common condition that may be caused by or coexist with other medical or psychological illnesses. Nearly a quarter of a billion people across the globe... (Review)
Review
INTRODUCTION
Insomnia is a common condition that may be caused by or coexist with other medical or psychological illnesses. Nearly a quarter of a billion people across the globe suffer from insomnia frequently. Lemborexant, a dual orexin receptor antagonist, is a recently authorized hypnotic-based medication for insomnia. The purpose of this systematic review is to further investigate its efficacy and safety profile, with the primary goal of comparing the effects of two FDA-approved doses of lemborexant, 5 mg and 10 mg (LEM5 and LEM10, respectively).
MATERIALS AND METHODS
PubMed, Google Scholar, ClinicalTrials.gov, and Cochrane Central were searched for relevant literature, and studies were considered if they compared the efficacy and safety of lemborexant 5 mg to lemborexant 10 mg. This study comprised clinical trials.
RESULTS
A total of 6 studies were evaluated for efficacy and safety of lemborexant therapy. They reported a significant betterment in values pertaining to sleep efficacy, sleep onset latency, wake after sleep onset, total sleep time, sleep quality, ISI score, and morning alertness. The results presented a dose-dependent pattern and showed slight variation with the different dosages. The most prevalent side effects noted were somnolence, headaches, and dizziness, with infections like UTIs and upper respiratory tract infections also being commonly reported. The incidence is rather ambiguous and not sincerely dose-dependent. The differences between results for LEM5 and LEM10 do not exhibit a wide variation, although slight dose-dependent alterations are noted.
CONCLUSION
Lemborexant is well integrated with the amelioration of sleep disturbances in insomniac patients, as shown by a decrease in eSOL and sWASO and a rise in sSE, sTST, quality of sleep, and morning alertness. Effects last 12 months after therapy.
Topics: Humans; Sleep Initiation and Maintenance Disorders; Pyridines; Pyrimidines; Hypnotics and Sedatives; Orexin Receptor Antagonists
PubMed: 36633778
DOI: 10.1007/s10072-023-06601-6 -
Sleep Medicine Reviews Oct 2022
Meta-Analysis
Topics: Humans; Network Meta-Analysis; Orexin Receptor Antagonists; Sleep Initiation and Maintenance Disorders
PubMed: 36007458
DOI: 10.1016/j.smrv.2022.101685 -
Sleep Medicine Reviews Oct 2022
Meta-Analysis
Reply to Wang et al.'s commentary on Xue et al.: The efficacy and safety of dual orexin receptor antagonists in primary insomnia: A systematic review and network meta-analysis.
PubMed: 36027793
DOI: 10.1016/j.smrv.2022.101686 -
International Clinical... Jan 2023Daridorexant is a novel dual orexin receptor antagonist used in treating insomnia disorder. Daridorexant improves sleep quality without impairing daytime functioning. We... (Meta-Analysis)
Meta-Analysis
Daridorexant is a novel dual orexin receptor antagonist used in treating insomnia disorder. Daridorexant improves sleep quality without impairing daytime functioning. We assess the safety and efficacy of this novel drug in the treatment of insomnia. We performed a systematic search for electronic databases in SCOPUS, PubMed, Web of Science and the Cochrane library. Seven randomized controlled trials were included in this review, with 2425 participants enrolled. Daridorexant was superior to placebo in reducing wake time after sleep onset (MD = -13.26; 95% CI, -15.48 to -11.03; P < 0.00001), latency to persistent sleep (MD = -7.23; 95% CI, -9.60 to -4.85; P < 0.00001), with increasing the total sleep time (MD = 14.80; 95% CI, 11.18-18.42; P < 0.00001) and subjective total sleep time (MD = 14.80; 95% CI, 11.18-18.42], P < 0.00001). The 25 mg and 50 mg were the most officious doses. Treatment with daridorexant has resulted in a slightly higher incidence of adverse events [risk ratio (RR) = 1.19; 95% CI, 1.05-1.35;, P = 0.005], specifically somnolence (RR = 1.19; 95% CI, 1.13-3.23; P = 0.005) and fatigue (RR = 2.01; 95% CI, 1.21-3.36; P = 0.007). Daridorexant is superior to placebo in improving sleep quality. However, the drug resulted in a slightly higher incidence of adverse events, including somnolence and fatigue.
Topics: Humans; Sleep Initiation and Maintenance Disorders; Randomized Controlled Trials as Topic
PubMed: 36473030
DOI: 10.1097/YIC.0000000000000425 -
Sleep Medicine Reviews Aug 2020The hypocretin system consists of two peptides hypocretin-1 and hypocretin-2 (HCRT1 and HCRT2). Hypocretin-containing neurons are located in the posterior and lateral...
The hypocretin system consists of two peptides hypocretin-1 and hypocretin-2 (HCRT1 and HCRT2). Hypocretin-containing neurons are located in the posterior and lateral hypothalamus, and have widespread projections throughout the brain and spinal cord. In addition to its presence in the cerebrospinal fluid (CSF), peripheral HCRT1 has been detected in plasma. Robust experimental evidence demonstrates functions of hypothalamic-originated HCRT1 in regulation of multiple biological systems related to sleep-wake states, energy homeostasis and endocrine function. In contrast, HCRT1 studies with human participants are limited by the necessarily invasive assessment of CSF HCRT1 to patients with underlying morbidity. Regulation by HCRT1 of energy homeostasis and reproduction in animals suggests similar regulation in humans and prompts these two systematic reviews. These reviews translate prior experimental findings from animal studies to humans and examine associations between HCRT1 and: 1) metabolic risk factors; 2) reproductive function in men, women and children. A total of 21 studies and six studies met the inclusion criteria for the two searches, respectively. Research question, study design, study population, assessments of HCRT1, reproductive, cardiometabolic data and main findings were extracted. Associations between HCRT1, metabolic and reproductive function are inconsistent. Limitations of studies and future research directions are outlined.
Topics: Animals; Cardiometabolic Risk Factors; Homeostasis; Humans; Hypothalamus; Neurons; Orexins; Plasma; Reproductive Health; Sleep
PubMed: 32259696
DOI: 10.1016/j.smrv.2020.101307 -
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 -
Neuroscience and Biobehavioral Reviews Jul 2019We aimed to perform a systematic review and meta-analysis of appetite regulating hormones in patients with first-episode psychosis (FEP). Meta-analyses were conducted... (Meta-Analysis)
Meta-Analysis
We aimed to perform a systematic review and meta-analysis of appetite regulating hormones in patients with first-episode psychosis (FEP). Meta-analyses were conducted using random-effects models with Hedges' g as the effect size estimate. We identified 31 eligible studies, investigating the levels of 7 appetite regulating hormones (adiponectin, insulin, leptin, ghrelin, orexin, resistin and visfatin) in 1792 FEP patients and 1364 controls. The insulin levels in FEP patients were higher than in controls (g = 0.34, 95%CI: 0.19 - 0.49, p < 0.001), even considering only antipsychotic-naïve patients (g = 0.39, 95%CI: 0.12 - 0.66, p = 0.005). The severity of negative symptoms was positively associated with the effect size estimates (β = 0.08, 95%CI: 0.01 - 0.16, p = 0.030). Moreover, we found lower levels of leptin in antipsychotic-naïve FEP patients (g = -0.62, 95%CI: -1.11 - 0.12, p = 0.015). Impaired appetite regulation, in terms of elevated insulin levels and decreased leptin levels, occurs in early psychosis, before antipsychotic treatment. Hyperinsulinemia might be related to negative symptoms.
Topics: Appetite Regulation; Humans; Insulin; Leptin; Obesity; Psychotic Disorders; Schizophrenia
PubMed: 31121198
DOI: 10.1016/j.neubiorev.2019.05.018 -
Journal of Experimental Pharmacology 2021Several effective pharmacological therapies for panic disorder (PD) are available, but they have some drawbacks, and unsatisfactory outcomes can occur. Expanding the... (Review)
Review
Several effective pharmacological therapies for panic disorder (PD) are available, but they have some drawbacks, and unsatisfactory outcomes can occur. Expanding the variety of anti-panic medications may allow for improving PD treatment. The authors performed an updated systematic review of preclinical and clinical (Phase I-III) pharmacological studies to look for advances made in the last six years concerning novel-mechanism-based anti-panic compounds or using medications approved for nonpsychiatric medical conditions to treat PD. The study included seven published articles presenting a series of preclinical studies, two Phase I clinical studies with orexin receptor (OXR) antagonists, and two clinical studies investigating the effects of D-cycloserine (DCS) and xenon gas in individuals with PD. The latest preclinical findings confirmed and expanded previous promising indications of OXR1 antagonists as novel-mechanism-based anti-panic compounds. Translating preclinical research into clinical applications remains in the early stages. However, limited clinical findings suggested the selective OXR1 antagonist JNJ-61393115 may exert anti-panic effects in humans. Overall, OXR1 antagonists displayed a favorable profile of short-term safety and tolerability. Very preliminary suggestions of possible anti-panic effects of xenon gas emerged but need confirmation with more rigorous methodology. DCS did not seem promising as an enhancer of cognitive-behavioral therapy in PD. Future studies, including objective panic-related physiological parameters, such as respiratory measures, and expanding the use of panic vulnerability biomarkers, such as hypersensitivity to CO panic provocation, may allow for more reliable conclusions about the anti-panic properties of new compounds.
PubMed: 33889031
DOI: 10.2147/JEP.S261403 -
BioMed Research International 2013There is a growing evidence that neuropeptides may be involved in the pathophysiology of suicidal behavior. A critical review of the literature was conducted to... (Meta-Analysis)
Meta-Analysis Review
There is a growing evidence that neuropeptides may be involved in the pathophysiology of suicidal behavior. A critical review of the literature was conducted to investigate the association between neuropeptides and suicidal behavior. Only articles from peer-reviewed journals were selected for the inclusion in the present review. Twenty-six articles were assessed for eligibility but only 22 studies were included. Most studies have documented an association between suicidality and some neuropeptides such as corticotropin-releasing factor (CRF), VGF, cholecystokinin, substance P, and neuropeptide Y (NPY), which have been demonstrated to act as key neuromodulators of emotional processing. Significant differences in neuropeptides levels have been found in those who have attempted or completed suicide compared with healthy controls or those dying from other causes. Despite cross-sectional associations between neuropeptides levels and suicidal behavior, causality may not be inferred. The implications of the mentioned studies were discussed in this review paper.
Topics: Arginine Vasopressin; Corticotropin-Releasing Hormone; Dynorphins; Galanin; Humans; Intracellular Signaling Peptides and Proteins; Neuropeptides; Orexins; Oxytocin; Substance P; Suicide
PubMed: 23986909
DOI: 10.1155/2013/687575 -
European Neuropsychopharmacology : the... Nov 2015Modafinil is an FDA-approved eugeroic that directly increases cortical catecholamine levels, indirectly upregulates cerebral serotonin, glutamate, orexin, and histamine... (Review)
Review
Modafinil is an FDA-approved eugeroic that directly increases cortical catecholamine levels, indirectly upregulates cerebral serotonin, glutamate, orexin, and histamine levels, and indirectly decreases cerebral gamma-amino-butrytic acid levels. In addition to its approved use treating excessive somnolence, modafinil is thought to be used widely off-prescription for cognitive enhancement. However, despite this popularity, there has been little consensus on the extent and nature of the cognitive effects of modafinil in healthy, non-sleep-deprived humans. This problem is compounded by methodological discrepancies within the literature, and reliance on psychometric tests designed to detect cognitive effects in ill rather than healthy populations. In order to provide an up-to-date systematic evaluation that addresses these concerns, we searched MEDLINE with the terms "modafinil" and "cognitive", and reviewed all resultant primary studies in English from January 1990 until December 2014 investigating the cognitive actions of modafinil in healthy non-sleep-deprived humans. We found that whilst most studies employing basic testing paradigms show that modafinil intake enhances executive function, only half show improvements in attention and learning and memory, and a few even report impairments in divergent creative thinking. In contrast, when more complex assessments are used, modafinil appears to consistently engender enhancement of attention, executive functions, and learning. Importantly, we did not observe any preponderances for side effects or mood changes. Finally, in light of the methodological discrepancies encountered within this literature, we conclude with a series of recommendations on how to optimally detect valid, robust, and consistent effects in healthy populations that should aid future assessment of neuroenhancement.
Topics: Benzhydryl Compounds; Cognition; Humans; Modafinil; Nootropic Agents
PubMed: 26381811
DOI: 10.1016/j.euroneuro.2015.07.028