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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 -
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 -
Neurobiology and Symptomatology of Post-Acute Alcohol Withdrawal: A Mixed-Studies Systematic Review.Journal of Studies on Alcohol and Drugs Jul 2022This study aims to review the neurobiology and symptomatology of post-acute alcohol withdrawal syndrome (PAWS).
OBJECTIVE
This study aims to review the neurobiology and symptomatology of post-acute alcohol withdrawal syndrome (PAWS).
METHOD
We conducted a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)-guided systematic review of articles from two databases for English-language randomized and nonrandomized studies involving PAWS published between database inception and December 2020.
RESULTS
Twenty-seven studies met inclusion criteria. PAWS involves predominantly negative affect, which develops in early abstinence and can persist for 4-6 months or longer. Symptoms include anxiety, dysphoria, anhedonia, sleep disturbance, cognitive impairment, cravings, and irritability. PAWS symptoms appear to be risk factors for recurrent alcohol consumption. They have been associated with reported neurobiological differences in evoked potentials; measures of orexins, cortisol, serotonin, and pancreatic polypeptides; and neuroadaptation changes in the nucleus accumbens and the prefrontal cortex.
CONCLUSIONS
There is credible evidence to support the concept of PAWS based on this review's findings. There remains a need to develop and test specific criteria for PAWS. High-quality treatment studies involving agents addressing its neurobiological underpinnings are also recommended.
Topics: Humans; Alcohol Drinking; Alcoholism; Craving; Neurobiology; Substance Withdrawal Syndrome
PubMed: 35838422
DOI: 10.15288/jsad.2022.83.461 -
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 -
Complex Psychiatry 2023Posttraumatic stress disorder (PTSD) is a complex multifactorial disorder influenced by the interaction of genetic and environmental factors. Analyses of epigenomic and... (Review)
Review
INTRODUCTION
Posttraumatic stress disorder (PTSD) is a complex multifactorial disorder influenced by the interaction of genetic and environmental factors. Analyses of epigenomic and transcriptomic modifications may help to dissect the biological factors underlying the gene-environment interplay in PTSD. To date, most human PTSD epigenetics studies have used peripheral tissue, and these findings have complex and poorly understood relationships to brain alterations. Studies examining brain tissue may help characterize the brain-specific transcriptomic and epigenomic profiles of PTSD. In this review, we compiled and integrated brain-specific molecular findings of PTSD from humans and animals.
METHODS
A systematic literature search according to the PRISMA criteria was performed to identify transcriptomic and epigenomic studies of PTSD, focusing on brain tissue from human postmortem samples or animal-stress paradigms.
RESULTS
Gene- and pathway-level convergence analyses revealed PTSD-dysregulated genes and biological pathways across brain regions and species. A total of 243 genes converged across species, with 17 of them significantly enriched for PTSD. Chemical synaptic transmission and signaling by G-protein-coupled receptors were consistently enriched across omics and species.
DISCUSSION
Our findings point out dysregulated genes highly replicated across PTSD studies in humans and animal models and suggest a potential role for the corticotropin-releasing hormone/orexin pathway in PTSD's pathophysiology. Further, we highlight current knowledge gaps and limitations and recommend future directions to address them.
PubMed: 37404872
DOI: 10.1159/000529536 -
Medicine Feb 2023Daridorexant is a novel dual orexin receptor antagonist that has shown efficacy as a treatment for insomnia in multiple randomized clinical trials. However, the efficacy... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Daridorexant is a novel dual orexin receptor antagonist that has shown efficacy as a treatment for insomnia in multiple randomized clinical trials. However, the efficacy and safety of daridorexant for treatment of insomnia disorder has not been characterized comprehensively in the literature. Therefore, we performed a meta-analysis of available studies. We performed a meta-analysis to systematically evaluate the efficacy and safety of daridorexant for treatment of insomnia disorder.
METHODS
MEDLINE, Embase, Cochrane Library, and Clinicaltrials.gov for randomized controlled trials were systematically searched up to February 2022. Relative risk and standard mean difference were used to evaluate clinical outcomes.
RESULTS
We pooled 2271 patients from 4 randomized clinical trials, and evaluated efficacy endpoints. We found that 50 mg of daridorexant was superior to placebo for 4 efficacy outcomes including wake time after sleep onset, latency to persistent sleep, subjective total sleep time, and Insomnia Daytime Symptoms and Impacts Questionnaire domain score (P < .05). In addition, there were no significant differences (P > .05) in adverse events between daridorexant and placebo.
CONCLUSIONS
Different dosages of daridorexant were tested for treatment of insomnia; however, 5 and 10 mg are not available because of issues of suboptimal effectiveness. Daridorexant showed better efficacy and safety for treatment of insomnia disorder at doses of 25 and 50 mg.
Topics: Humans; Sleep Initiation and Maintenance Disorders; Randomized Controlled Trials as Topic; Imidazoles; Pyrrolidines
PubMed: 36800596
DOI: 10.1097/MD.0000000000032754 -
The International Journal of... Feb 2024Cannabis use is a risk factor of psychiatric illness, such as bipolar disorder type-I (BDI). Indeed, cannabis use strongly influences the onset and clinical course of...
BACKGROUND
Cannabis use is a risk factor of psychiatric illness, such as bipolar disorder type-I (BDI). Indeed, cannabis use strongly influences the onset and clinical course of BDI, although the biological mechanisms underlying this interaction remain unknown. Therefore, we have reviewed the biological mechanisms affected by cannabis use that may trigger BD.
METHODS
A systematic review was carried out of articles in which gene expression was studied in cannabis users or human-derived cells exposed to tetrahydrocannabinol (THC) or cannabidiol (CBD). A second systematic review was then performed to identify articles in which gene expression was studied in BDI samples, highlighting those that described alterations to the same molecular and cellular mechanisms affected by cannabis/THC/CBD.
RESULTS
The initial search identified 82 studies on cannabis and 962 on BDI. After removing duplicates and applying the inclusion/exclusion criteria, 9 studies into cannabis and 228 on BDI were retained. The molecular and cellular mechanisms altered by cannabis use or THC/CBD exposure were then identified, including neural development and function, cytoskeletal function, cell adhesion, mitochondrial biology, inflammatory related pathways, lipid metabolism, the endocannabinoid system, the hypocretin/orexin system, and apoptosis. Alterations to those activities were also described in 19 of 228 focused on BDI.
CONCLUSIONS
The biological mechanisms described in this study may be good candidates to the search for diagnostic biomarkers and therapeutic targets for BDI. Because cannabis use can trigger the onset of BD, further studies would be of interest to determine whether they are involved in the early development of the disorder, prompting early treatment.
Topics: Humans; Cannabis; Bipolar Disorder; Cannabinoid Receptor Agonists; Cannabidiol; Hallucinogens; Risk Factors; Dronabinol
PubMed: 38175142
DOI: 10.1093/ijnp/pyae002 -
Sleep Medicine Sep 2023Narcolepsy type 1 is a primary sleep disorder caused by deficient hypocretin transmission leading to excessive daytime sleepiness and cataplexy. Opioids have been...
OBJECTIVE
Narcolepsy type 1 is a primary sleep disorder caused by deficient hypocretin transmission leading to excessive daytime sleepiness and cataplexy. Opioids have been suggested to increase the number of hypocretin-producing neurons. We aimed to assess opioid use and its self-reported effect on narcolepsy type 1 symptom severity through a literature review and questionnaire study.
METHODS
We systematically reviewed literature on opioid use in narcolepsy. We also recruited 100 people with narcolepsy type 1 who completed an online questionnaire on opioid use in the previous three years. The main questionnaire topics were the indication for use, and the possible effects on narcolepsy symptom severity. Structured follow-up interviews were conducted when opioid use was reported.
RESULTS
The systematic literature review mainly showed improvements in narcolepsy symptom severity. Recent opioid use was reported by 16/100 questionnaire respondents, who had used 20 opioids (codeine: 7/20, tramadol: 6/20, oxycodone: 6/20, fentanyl: 1/20). Narcolepsy symptom changes were reported in 11/20. Positive effects on disturbed nocturnal sleep (9/20), excessive daytime sleepiness (4/20), hypnagogic hallucinations (3/17), cataplexy (2/18), and sleep paralysis (1/13) were most pronounced for oxycodone (4/6) and codeine (4/7).
CONCLUSIONS
Opioids were relatively frequently used compared to a similarly young general Dutch sample. Oxycodone and, to a lesser extent, codeine were associated with self-reported narcolepsy symptom severity improvements. Positive changes in disturbed nocturnal sleep and daytime sleepiness were most frequently reported, while cataplexy effects were less pronounced. Randomised controlled trials are now needed to verify the potential of opioids as therapeutic agents for narcolepsy.
Topics: Humans; Cataplexy; Analgesics, Opioid; Orexins; Oxycodone; Narcolepsy; Disorders of Excessive Somnolence; Surveys and Questionnaires
PubMed: 37437491
DOI: 10.1016/j.sleep.2023.06.008 -
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 -
Frontiers in Pharmacology 2022Therapeutic management of depression has currently important limitations, and its low efficacy is reflected in high rates of non-response even after multiple trials of...
Therapeutic management of depression has currently important limitations, and its low efficacy is reflected in high rates of non-response even after multiple trials of antidepressants. Almost two-thirds of the patients diagnosed with major depression who received a 4-6 weeks trial of antidepressant could not reach remission, and more than 30% of these patients are considered treatment-resistant. In bipolar depression, the situation is also discouraging if we analyze the high suicide rate, the risk for the treatment-emergent affective switch when antidepressants are added, the high rate of treatment resistance (up to 25%), and the severe functional impairments associated with these episodes. Therefore, new therapeutic agents are needed, as well as new pathogenetic models for depression. The vast majority of the currently approved antidepressants are based on the monoamine hypothesis, although new drugs exploiting different neurotransmitter pathways have been recently approved by FDA. Brexanolone, an allopregnanolone analog, is an example of such new antidepressants, and its approval for post-partum depression inspired the search for a new generation of neurosteroids and GABA-ergic modulators, with an easier way of administration and superior tolerability profile. Orexin receptors antagonists are also extensively studied for different psychiatric disorders, depression included, in phase II trials. Antiinflammatory drugs, both cyclo-oxygenase 2 inhibitors and biological therapy, are investigated in patients with depressive disorders based on the proven correlation between inflammation and mood disorders in preclinical and clinical studies. Also, a new generation of monoamine-based investigational drugs is explored, ranging from triple reuptake inhibitors to atypical antipsychotics, in patients with major depression. In conclusion, there is hope for new treatments in uni- and bipolar depression, as it became clear, after almost seven decades, that new pathogenetic pathways should be targeted to increase these patients' response rate.
PubMed: 35774601
DOI: 10.3389/fphar.2022.884143