Sodium oxybate 500mg/ml oral solution sugar free

BACKGROUND: Worldwide, three million deaths each year are reported due to the harmful use of alcohol. To date, only a few drugs have been approved for the treatment of Alcohol Use Disorder (AUD). This systematic review and meta-analysis aim to assess the long-term efficacy and safety of sodium oxybate (SMO) treatment in patients with AUD. METHODS: We followed the PRISMA statement guidelines and searched PubMed and ISI Web of Science to retrieve the studies of interest. In total, 13 studies on long-term (>12 weeks) SMO administration in patients with AUD were included in this systematic review, and 7 were included in the metaanalysis. RESULTS: Overall, the abstinence rate after 12 weeks of treatment was similar in the SMO and placebo groups, while it was significantly in favour of SMO compared to Naltrexone (NTX). The completion rate was similar in all three conditions. Mean corpuscular volume (MCV) levels favoured SMO over NTX, while Alcohol Craving Scale (ACS) scores did not favour SMO. The incidence of adverse reactions varied widely between studies. CONCLUSION: SMO in the chronic treatment of patients with AUD showed no superiority to placebo in our analysis of published RCTs, although many observational studies reported its beneficial effect in the long term. On the contrary, SMO was superior to NTX treatment on abstinence. The rate of study completion was similar in the three groups. Safety was not an issue in any of the studies included. Further studies are needed to better assess SMO efficacy and safety in the long term.

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Narcolepsy, a central hypersomnolence disorder, disrupts sleep regulation. Sodium oxybate, a CNS (central nervous system) depressant, is widely used as a treatment, but there are surprisingly very few rigorous studies comparing its effectiveness to placebo in adults. To measure the comparative efficacy of sodium oxybate at a dosage regimen of 9 g versus placebo in improving nighttime sleep quality, reducing nocturnal arousals and sleep stage shifts, and enhancing the overall refreshed nature of sleep in adult patients with narcolepsy. The methodology included a literature review of PubMed, Cochrane, Scopus, Google Scholar, and Clinicaltrials.gov, retrieving 53 randomized controlled trials (RCT) after removing 14 duplicates. Four studies met the criteria for gauging the efficacy of sodium oxybate compared to placebo in the adult population with narcolepsy. The primary efficacy outcome was improved sleep quality, whereas secondary outcomes were reduced nocturnal arousals and sleep stage shifts with an overall refreshed sleep nature. Analyses used RevMan 5.3 software, and SMD (standardized mean differences) with 95 % CI (confidence intervals) were calculated. Risk and publication biases were measured with Cochrane risk of bias tools and Comprehensive Meta-Analysis Software. Evidence certainty was measured using GRADEpro. Four RCT involving 1079 participants were analyzed for said outcomes, and relevant forest plots were generated. Statistical analysis showed a substantial improvement in sleep quality [SMD = 0.74(95%Cl:0.53,0.95; p < 0.00001; I 2 = 0 %; (high certainty)] and refreshing nature of sleep [SMD = 0.81(95%CI:0.51,1.11; P < 0.00001; I 2 = 0 %; (moderate certainty)], reduction in nocturnal arousals [SMD = −0.62(95%CI: 0.92,-0.32; p < 0.00001; I 2 = 0 %; (moderate certainty)] and sleep stage shifts [SMD = −1.22(95%CI: 1.46,-0.98; p < 0.00001; I 2 = 0 %; (high certainty)]. The risk of bias was located high for one study. Symmetrical funnel plots and Egger's regression intercepts testified to no significant publication bias. The results showed that sodium oxybate considerably improved the quality of nocturnal sleep, resulting in substantial restorative advantages as well as a decrease in nocturnal arousals and sleep stage transitions. Significant results with low heterogeneity and p-values <0.05, showing consistent effects, were obtained from the analysis. However, overall reliability may be impacted by a high risk of bias in one study. • This meta-analysis the efficacy of Sodium Oxybate on improvement of nighttime sleep in adult patients with narcolepsy. • A specific focus was put for 9g dosing regimen and adult patients with narcolepsy and no co-morbid conditions. • Results of efficacy measures calculated as of standardized mean differences (SMDs) with 95 % confidence intervals were accompanied by statistically significant p-values, minimal heterogeneity and minimal. • The minimal peril associated with the quality of bias assessment, the absence of publication bias, and the high level of evidence certainty collectively understood the robustness of the results. • Our analysis that Sodium Oxybate at a dose of 9g exhibits a clinically significant efficacy in improving nighttime sleep quality, reducing nocturnal arousals and sleep stage shifts, and enhancing the overall refreshed nature of sleep in adult patients with narcolepsy, signalling its relevance and critical need for optimized therapeutic interventions.

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Low-sodium oxybate (LXB; Xywav®) is approved to treat idiopathic hypersomnia in adults and excessive daytime sleepiness or cataplexy in individuals aged ≥ 7 years with narcolepsy. The efficacy and safety of LXB have been demonstrated in randomized controlled trials. This study will comprehensively evaluate multiple daytime and nighttime symptoms in participants with idiopathic hypersomnia and participants with narcolepsy treated with LXB. Jazz DUET (Develop hypersomnia Understanding by Evaluating low-sodium oxybate Treatment; NCT05875974) is a prospective, multi-cohort, multicenter, single-arm, open-label, interventional study. Establishing multiple cohorts across different diseases aligns with more generalizable research designs enabling a broader impact. Total study duration is ~ 10–21 weeks, which includes a 2- to 6-week screening period, an 8-day baseline period, a 2- to 8-week titration period, a 2-week stable-dose period, a 1- to 2-week end-of-treatment assessment period, and a 2-week safety follow-up period. To provide a robust dataset of changes with LXB treatment which will inform healthcare providers and their patients, DUET is administering a wide range of patient- and clinician-reported outcome assessments regarding symptom severity and daytime functioning and includes objective measures of sleep (ad libitum polysomnography protocol) and sleep inertia which have not been previously tested with this type of study design. Additionally, pharmacokinetics data and clinician titration feedback are collected to inform titration/dosing guidance for clinicians. DUET was designed in a patient-centric manner to reflect a real-world approach to conducting clinical trials. Using a patient-centric design aiming to address participants’ burden and improve their study experience, the DUET study will fill critical idiopathic hypersomnia and narcolepsy evidence gaps pertaining to sleep architecture (e.g., disrupted nighttime sleep) and response to LXB treatment, as well as provide data on outcomes that are meaningful to patients. Graphical abstract available for this article. Low-sodium oxybate (LXB; Xywav®) is a medicine that people living with idiopathic hypersomnia or narcolepsy take to feel less sleepy. People with narcolepsy also take LXB to treat cataplexy (sudden muscle weakness from strong emotions). However, these patients experience other symptoms beyond sleepiness and cataplexy. People with idiopathic hypersomnia often do not feel refreshed after sleeping. They also wake up feeling groggy, confused, and irritable (sleep inertia). People with narcolepsy often have trouble sleeping well at night. They wake up a lot or are unable to stay in deep sleep (disrupted nighttime sleep). Individuals with either disorder often have concentration and memory problems (cognitive dysfunction), have a low mood, and are unable to complete daily tasks. How does LXB impact these symptoms? Addressing this question requires a research study with many different tests. Completing all these tests could make people not want to participate, especially if they do not understand the importance of the tests. Studies need to be designed to determine what matters most to patients, while considering testing burden. Jazz’s DUET study was designed in this way. DUET asked real patients to suggest ways to make the study more participant-friendly. Suggestions included to allow more breaks between tests, educate on why this study is important, and provide participants with their own sleep data reports. These suggestions were used in the study design. DUET was able to look at the association of LXB with a wide range of meaningful, relevant symptoms, while prioritizing participants’ well-being and study experience.

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Postoperative delirium (POD) represents a significant challenge in perioperative care, particularly among older surgical patients. This acute neuropsychiatric syndrome is associated with prolonged hospitalization, increased mortality, and long-term cognitive decline. Sleep disturbance has emerged as a significant modifiable risk factor for POD. Sodium oxybate (SO), a gamma-aminobutyric acid B (GABAB) receptor agonist with established sleep-enhancing properties, presents a promising therapeutic approach for POD prevention. The objective of this trial was to investigate whether prophylactic intraoperative sodium oxybate reduces POD incidence in older patients (≥ 65 years) undergoing major orthopedic surgery. This randomized, double-blind, placebo-controlled trial enrolled 332 older patients undergoing elective spine and joint replacement surgery. Participants received either sodium oxybate (30 mg kg−1) or saline after anesthetic induction. Stratified randomization allocated equal numbers to morning and afternoon surgery groups. The primary outcome was POD incidence within seven postoperative days, assessed using the Confusion Assessment Method (CAM). POD incidence showed no significant difference between groups in unstratified population (10.3% vs. 13.5%, P = 0.372). However, subgroup analysis revealed protective effects in morning surgery patients (7.3% vs. 18.5%, relative risk (RR) = 0.395, 95% confidence intervals (CI) = 0.161–0.968, P = 0.033), while no effect was observed in the afternoon surgery group (13.3% vs. 8.5%, P = 0.318). Among patients with delirium, no significant differences were observed in delirium severity, onset timing, delirium duration, or subtype distribution after false discovery rate (FDR) correction. No significant differences were found in sleep quality, maximal pain score, or safety parameters between groups after FDR correction. Intraoperative sodium oxybate demonstrates possible time-specific efficacy, significantly reducing POD incidence exclusively in older patients undergoing morning orthopedic surgery, while demonstrating an acceptable safety profile with no significant adverse effects on anesthesia recovery or hemodynamic parameters, suggesting a potential chronotherapeutic approach to POD prevention. Chinese Clinical Trial Registry, ChiCTR2300078594. Registered on 2023–12-13.

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Purpose: Individuals with narcolepsy are more likely to be obese than the general population.Changes in weightrelated measures with extended-release, once-nightly sodium oxybate (ON-SXB) and characteristics of participants with 5% weight loss were assessed in a Randomized study Evaluating the efficacy and SafeTy of a ONce nightly formulation of sodium oxybate (REST-ON) trial post hoc analysis.Methods: REST-ON (NCT02720744) was a Phase III, double-blind, placebo-controlled, multicenter, randomized clinical trial.Participants aged 16 years with narcolepsy type 1 (NT1) or NT2 received ON-SXB or placebo for 13 weeks (week 1, 4.5 g; weeks 2-3, 6 g; weeks 4-8, 7.5 g; and weeks 9-13, 9 g).Weight and body mass index were measured at baseline and study end.Findings: Weights were similar between groups at baseline (mean [SD]; ON-SXB, 81.2 [20.8] kg; N = 107 [NT1, n = 80; NT2, n = 27]; placebo, 82.1 [22.5] kg; N = 105 [NT1, n = 82; NT2, n = 23]).At week 13 (9 g), mean (SD) weight decreased 1.3 (3.6) kg with ON-SXB and increased 0.2 (2.6) kg with placebo; 17.8% (19/107; NT1, n = 14; NT2, n = 5) of participants receiving ON-SXB had 5% weight loss versus 3.8% receiving placebo (4/105; NT1, n = 3; NT2, n = 1; P = 0.001).At week 13, least squares mean (SE) body mass index change from baseline was -0.51 (0.13) kg/m 2 with ON-SXB and 0.08 (0.13) kg/m 2 with placebo (least squares mean difference [95% CI], -0.59 [-0.95 to -0.23] kg/m 2 ; P = 0.001).Excessive daytime sleepiness improved for both groups with ON-SXB, the 5% weight-loss subgroup exhibited larger improvement in the Maintenance of Wakefulness Test and Epworth Sleepiness Scale versus the other subgroup (weight loss < 5%, no change, or weight gain) (Maintenance of Wakefulness Test, P = 0.019; Epworth Sleepiness Scale score, P < 0.001).Implications: Narcolepsy is often associated with obesity, which may increase cardiometabolic risks.ON-SXB, an effective treatment for excessive daytime sleepiness and cataplexy, may be preferred in overweight or obese individuals to provide a more tailored treatment approach.ClinicalTrials.

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Narcolepsy is a rare, chronic sleep disorder with significant impacts on the quality of life of people affected by the disorder. People with narcolepsy (PWN) are a diverse patient population with evolving symptoms, comorbidities, and perspectives. As PWN have varying needs, clinicians should consider a more personalized approach to therapy, including active participation of PWN in their care and shared decision-making between patient and clinician to achieve optimal outcomes. In this review, we discuss the various characteristics and challenges of PWN, present illustrative clinical case scenarios of PWN, provide clinicians with a proposed framework to best address therapy for PWN, and demystify concerns with sodium oxybate.

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Alcohol dependence (AD) significantly impacts public health, affecting 3.4% of people aged 18-64 and contributing to around 12% of overall mortality. Individuals with AD have a markedly reduced life expectancy, dying up to 28 years earlier than the general population. Current treatments for AD show limited efficacy, with many patients not responding to these interventions, highlighting the need for new therapeutic options with novel mechanisms of action. Sodium oxybate (SMO), the sodium salt of GHB, is one such candidate, pharmacologically similar to alcohol; it acts on several neurotransmitters including GABA, potentially mitigating withdrawal symptoms and craving for alcohol. SMO has been clinically used in Italy and Austria since the 1990s, approved for treating alcohol withdrawal syndrome (AWS) and for maintaining abstinence in AD patients. Several randomized clinical trials (RCTs) and meta-analyses showed evidence of SMO to be effective and safe in these indications. For AWS, SMO was more effective than placebo and as effective as benzodiazepines in reducing withdrawal symptoms. For maintaining abstinence, SMO significantly improved continuous abstinence duration and abstinence rate compared to placebo. Comprehensive clinical data indicate that SMO is well-tolerated, with main adverse effects being mild, such as dizziness and vertigo, and serious adverse events being rare. The effectiveness and safety of SMO, coupled with its approval in two EU countries affirm its potential as a treatment option for AD, particularly in severe cases. Further RCTs, especially with stratification by severity of dependence, are suggested to refine our understanding of its efficacy across different patient subgroups.

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Introduction Narcolepsy is a rare but disabling neurological disorder involving disruption of the sleep-wake cycle that is often under- or misdiagnosed (Barateau L, et al . J Sleep Res. 2022;31(4):e13631). It is characterized by a classical tetrad of excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations, and sleep paralysis. Narcolepsy is divided into 3 types: Narcolepsy Type 1 (NT1); Narcolepsy Type 2 (NT2); and Secondary Narcolepsy. The pathophysiology remains unclear but is primarily associated with loss of hypocretin (orexin) neurons involving autoimmune and genetic risk factors, particularly for NT1. Objectives To review the currently available therapies for the treatment of narcolepsy. Methods The extant literature was reviewed and discussed in the context of clinical relevance. Results Treatment historically has included medications developed for the treatment of other conditions such as psychostimulants (methylphenidate, modafinil/armodafinil, pemoline) and antidepressants (SSRIs,TCAs). These agents are also associated with limiting side effects in practice. In more recent years a variety of specific treatments have been approved that act on diverse pathways. Pitolisant, a histamine H3 receptor inverse agonist, is approved for the treatment of EDS or cataplexy in adult patients with narcolepsy (and children&gt; 6 years in European Union) (Keam SJ.Paediatr Drugs. 2023;25(4):483-488). Solriamfetol, a dopamine and norepinephrine reuptake inhibitor (DNRI) is indicated to improve wakefulness in adult patients with EDS associated with narcolepsy or obstructive sleep apnea (OSA) (Winter Y, et al. Sleep Med. 2023;103:138-143). Sodium oxybate (SXB), a GABA B receptor agonist, is approved for the treatment of cataplexy associated with narcolepsy and (EDS) in patients 7 years or older (Bogan RK, et al. CNS Drugs. 2023;37(4):323-335). Current research focuses on on-peptide hypocretin receptor-2 agonists (Saitoh T, Sakurai T. Peptides. 2023;167:171051). Conclusions Despite limited understanding of the pathophysiology of narcolepsy there have been substantial advances in the pharmacotherapy, including medications now approved for children. Early diagnosis and treatment are associated with better outcomes. In view of the chronic and disabling morbidity associated with narcolepsy further research and better access to appopriate medications is necessary. Disclosure of Interest None Declared

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