Clinical practice guidelines for switching or deprescribing hypnotic medications for chronic insomnia: results of European neuropsychopharmacology and sleep expert’s consensus group

Sleep Medicine, Journal Year: 2025, Volume and Issue: 128, P. 117 - 126

Published: Jan. 31, 2025

Language: Английский

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Early experience with the new DORA daridorexant in patients with insomnia disorder and comorbid mental disturbances: Results of a naturalistic study with 3 months follow‐up

Journal of Sleep Research, Journal Year: 2024, Volume and Issue: unknown

Published: March 24, 2024

Summary Insomnia disorder may affect mental health, increasing suicidal risk. Targeting insomnia is crucial in the clinical practice. Sixty‐six consecutive patients with according DSM‐5‐TR criteria were treated dual orexin receptor antagonist, daridorexant 50 mg. Baseline (T0), 1 month (T1) and 3 (T2) evaluations performed. severity (Insomnia Severity Index), mood, anxiety symptoms risk (Beck Depression Inventory‐II, Young Mania Rating Scale, Self‐Reported Anxiety Suicidal Ideation Scale), dysfunctional insomnia‐cognitive factors pre‐sleep arousal (Dysfunctional Beliefs About Sleep, Pre‐Sleep Arousal Scale) evaluated. The final sample included 66 ( n = 36, 54% females, mean age 60 ± 13.6 years). Most of them, 64%, suffered from comorbid unipolar/bipolar depression, disorders substance use disorders. Repeated ANOVA analyses showed that Index, Dysfunctional Sleep Scale total score decreased across time F 68.818, p < 0.001; 47.561, 28.142, 0.001, respectively). Similarly, Beck significantly over 0.001). Predictors remission Index 8) at T1 improvement 60.205, 0.001), 4.432, 0.041). T2 was best predicted by 3.993, 0.023). Multiple‐regression models Inventory‐II T2, manic somatic T2. With caution a naturalistic design, early experience targeting it be possible to improve not only but also symptoms.

Language: Английский

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Novel Urea-Containing Compounds as Orexin Receptor Agonists for Treating Sleep Disorders, Namely, Narcolepsy, Hypersomnia, and Sleep Apnea Syndrome

ACS Medicinal Chemistry Letters, Journal Year: 2025, Volume and Issue: 16(3), P. 375 - 376

Published: Feb. 18, 2025

Provided herein are novel urea-containing compounds as orexin receptor agonists, pharmaceutical compositions, use of such in treating sleep disorders, namely, narcolepsy, hypersomnia, and apnea syndrome well processes for preparing compounds.

Language: Английский

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Early life stress and hormonal status influence orexin‐1 receptor expression in structures regulating cardiorespiratory responses to CO₂

Experimental Physiology, Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

Abstract Excessive cardiorespiratory responses to CO 2 are a hallmark of panic disorder (PD). Female sex and exposure early life stress risk factors for PD. Neonatal maternal separation (NMS; 3 h/day, postnatal days 3–12) augments the ventilatory response by ∼35% relative controls; this effect is most notable during pro‐oestrus but not observed in males. Orexin‐1 receptor (OX1‐R) antagonism attenuates NMS females. In limbic system, ovarian hormones influence OX1‐R expression, impact these on OX1‐Rs regions regulating unknown. Here, we hypothesised that determine expression structures response; used situ hybridisation quantify OX‐1R mRNA brains adult control rats. Brains were harvested from females either (high hormones) or weeks post ovariectomy (OVX; low hormones); males included comparison. Hormonal status influenced intensity signal medial amygdala, raphe obscurus (RObs) A5 area, direction changes (increase vs. decrease) was structure‐specific. Significant × hormonal interactions noted dorsal raphe, locus coeruleus, nucleus solitary tract area; effects As only structure which matched sex‐specific response, likely contributes respiratory manifestations

Language: Английский

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A Preliminary Report on the Effects of Daridorexant in Patients with Comorbid Insomnia and Substance Use Disorders

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(3), P. 378 - 378

Published: March 6, 2025

Background. Sleep disturbances are frequent in patients with substance use disorders (SUDs) and associated craving addiction relapses, leading to increased clinical severity detrimental outcomes. Daridorexant, a selective dual orexin receptor antagonist, has been approved for persistent insomnia disorder (ID), but specific insights on SUDs lacking. Methods. This observational, retrospective study investigated the effects of three-month treatment daridorexant (50 mg/day) 41 outpatients comorbid IDs SUDs. Improvement subjective sleep measures, assessed Insomnia Severity Index (ISI) total time, was primary outcome measure. Changes anxiety depression symptoms, quality life, global severity, were also through following: Hamilton Anxiety Depression Rating Scale; Five-item World Health Organization Well-Being Index; Clinical Global Impression Visual Analog Scale Craving. Results. All outcomes significantly improved throughout treatment, which generally safe well tolerated, mild transient drowsiness sluggishness reported 21.1% patients. Similar improvements observed psychopathology, craving, positive correlations found among ISI scores anxiety/depression symptoms craving. An abstinence rate (i.e., absence any use, regardless amount, treatment) 65.8% detected at endpoint. Conclusions. These preliminary findings suggest that might represent promising tool treating Identifying interventions effectively targeting good safety/tolerability profile is crucial achieve remission full functional recovery.

Language: Английский

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Nanoparticles targeting the central circadian clock: Potential applications for neurological disorders

Advanced Drug Delivery Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 115561 - 115561

Published: March 1, 2025

Circadian rhythms and their involvement with various human diseases, including neurological disorders, have become an intense area of research for the development new pharmacological treatments. The location circadian clock machinery in central nervous system makes it challenging to reach molecular targets at therapeutic concentrations. In addition, a timely administration agents is necessary efficiently modulate clock. Thus, use nanoparticles dysfunctions may accelerate clinical translation by addressing these two key challenges: enhancing brain penetration and/or enabling formulation chronodelivery systems. This review describes implications pathologies, reviews potential modulators suggests how nanoparticle-based formulations could improve success. Finally, integration into chronopharmaceutical drug delivery systems will be described.

Language: Английский

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Cerebrospinal-fluid Orexin-A levels in different neurocognitive disorders: a comparison study

Neurological Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: April 8, 2025

Abstract In the present study, we investigated differences in cerebrospinal fluid (CSF) orexin-A levels among patients with different neurocognitive disorders, such as mild or moderate to severe Alzheimer’s disease (AD; mAD, msAD, respectively), behavioral variants of frontotemporal dementia (bv-FTD), non-fluent primary aphasia (NFPA), and idiopathic normal pressure hydrocephalus (iNPH). A total 214 participants were evaluated (mAD, 45; 31; bv-FTD, 12; NFPA, 22; iNPH, 13; non-demented elderly controls, 91). The highest CSF found iNPH (263.31 ± 56.89 pg/mL). Patients affected by NFPA (210.86 61.99 pg/mL), msAD (173.04 19.76 pg/mL) showed higher concentrations than controls (145.18 27.01pg/mL) ( p < 0.001). Bv-FTD (190.12 100.84 mAD (130.76 21.70 no significant compared controls. also lower all other patient groups. conclusion, presents disorders. mechanisms underlying this difference vary may include sleep-wake cycle impairment, disturbances, dynamics. development drugs that antagonize orexin system could open a new frontier research linking neurotransmission

Language: Английский

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Reevaluating orexin-a as a biomarker across dementia subtypes: clinical implications and future directions, a letter to editor

Neurological Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Language: Английский

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Insomnia and the Orexinergic Pathway in the Link with Psychopathology: Effects of DORAs in Insomnia Comorbid with Mental Disturbances

Current Sleep Medicine Reports, Journal Year: 2024, Volume and Issue: 10(2), P. 119 - 131

Published: April 18, 2024

Language: Английский

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Daridorexant treatment for chronic insomnia: a real-world retrospective single-center study

Neurological Sciences, Journal Year: 2024, Volume and Issue: 45(7), P. 3443 - 3448

Published: Jan. 27, 2024

Chronic insomnia disorder (CID) significantly impacts well-being and daily functioning. Daridorexant, a double orexin receptor blocker, has shown efficacy in randomized clinical trials been recently approved for the treatment of CID adult patients. This retrospective observational study aimed to describe real-world data on daridorexant effectiveness safety patients with CID.

Language: Английский

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