Sodium acetate 3mmol/50ml / Sodium oxybate 2mmol/50ml / Sodium propionate 1.5mmol/50ml enema

AIMS: The estimated effect of sodium oxybate (SMO) in the treatment of alcohol dependence is heterogeneous. Population severity and treatment duration have been identified as potential effect modifiers. Population severity distinguishes heavy drinking patients with <14 days of abstinence before treatment initiation (high-severity population) from other patients (mild-severity population). Treatment duration reflects the planned treatment duration. This study aimed to systematically investigate the effect of these potential effect moderators on SMO efficacy in alcohol-dependent patients. METHODS: Network meta-regression allows for testing potential effect modifiers. It was selected to investigate the effect of the above factors on SMO efficacy defined as continuous abstinence (abstinence rate) and the percentage of days abstinent (PDA). Randomized controlled trials for alcohol dependence with at least one SMO group conducted in high-severity and mild-severity populations were assigned to a high-severity and mild-severity group of studies, respectively. RESULTS: Eight studies (1082 patients) were retained: four in the high-severity group and four in the mild-severity group. The high-severity group was associated with larger SMO effect sizes than the mild-severity group: abstinence rate risk ratio (RR) 3.16, P = 0.004; PDA +26.9%, P < 0.001. For PDA, longer treatment duration was associated with larger SMO effect size: +11.3% per extra month, P < 0.001. In the high-severity group, SMO showed benefit: abstinence rate RR 2.91, P = 0.03; PDA +16.9%, P < 0.001. In the mild-severity group, SMO showed benefit only in PDA for longer treatment duration: +23.9%, P < 0.001. CONCLUSIONS: In the retained studies with alcohol-dependent patients, high-severity population and longer treatment duration were associated with larger SMO effect sizes.

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OBJECTIVE: To examine the efficacy and safety of sodium oxybate versus placebo in a phase IIb randomized double-blind placebo-controlled 2-period cross-over clinical trial in patients with isolated laryngeal dystonia (LD). METHODS: The study was conducted from January 2018 to December 2021, pausing during the COVID-19 pandemic, at Massachusetts Eye and Ear in 106 patients with alcohol-responsive (EtOH+) and alcohol-non-responsive (EtOH-) LD (53 to receive 1.5g of sodium oxybate first, 53 to receive matching placebo first). The primary outcome was a change from baseline in LD symptom severity 40 minutes after drug intake. Safety was based on vital signs, cognitive function, suicidality, daytime sleepiness, and adverse events. Patients, investigators, and outcome assessors were masked to study procedures. RESULTS: Compared to baseline, EtOH+ but not EtOH- patients had a statistically significant improvement in LD symptoms following sodium oxybate versus placebo (EtOH+: 98.75% confidence interval [CI] = 0.6-26.9; p = 0.008; EtOH-: 98.75% CI = -6.2 to 18.7; p = 0.42). Statistically significant minimum drug efficacy in EtOH+ patients was found at ≥16% symptom improvement (OR = 2.09; 98.75% CI = 0.75-5.80; p = 0.036), with an average of 40.81% benefits (98.75% CI = 34.7-48.6). Drug efficacy waned by 300 minutes after intake without a rebound. No changes were found in cognitive function, suicidality, or vital signs. Common adverse events included mild dizziness, nausea, and daytime sleepiness. INTERPRETATION: Sodium oxybate showed clinically meaningful improvement of symptoms in EtOH+ LD patients, with acceptable tolerability. Sodium oxybate offers the first pathophysiologically relevant oral treatment for laryngeal dystonia. ANN NEUROL 2025;97:329-343.

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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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Abstract: Narcolepsy and idiopathic hypersomnia are chronic conditions that negatively affect alertness, mental and physical energy, functioning, and quality of life (QoL). Calcium, magnesium, potassium, and sodium oxybates (low-sodium oxybate; LXB) is an oxybate formulation with 92% less sodium than sodium oxybate (SXB; a treatment for narcolepsy) and the same active moiety. LXB is approved in the US for treatment of cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age or older with narcolepsy, and idiopathic hypersomnia in adults. In Phase 3 clinical trials, LXB exhibited a safety profile consistent with that of SXB in narcolepsy. Besides continued efficacy in treating symptoms, potential benefits of long-term LXB treatment include flexible optimization of dosing and regimen, improvement of QoL and functioning, weight loss, and (relative to SXB in narcolepsy) health benefits of reduced sodium content. Dosing of LXB is twice nightly (for narcolepsy) or once or twice nightly (for idiopathic hypersomnia) based on patient characteristics and response, and individualized titration can be leveraged over the long term as a patient’s life circumstances change. Patients with narcolepsy transitioning from SXB initiate LXB at the same dose, and most patients require no further changes to achieve similar efficacy and tolerability. Improvements in functioning and QoL with LXB treatment could have cascading positive effects in multiple domains, particularly in younger patients. In clinical trials, LXB was associated with weight loss in both narcolepsy (in which obesity is a well-established comorbidity) and idiopathic hypersomnia, only occasionally leading participants to be underweight. As both narcolepsy and idiopathic hypersomnia are associated with increased risk of cardiometabolic and cardiovascular comorbidities, limiting medication-related sodium intake with LXB may have significant health benefits, although this has not yet been verified prospectively due to the prolonged follow-up required. LXB is a promising long-term treatment for narcolepsy and idiopathic hypersomnia. Plain Language Summary: Narcolepsy and idiopathic hypersomnia are disorders that make people feel very sleepy. Low-sodium oxybate (LXB) is a medicine for these disorders. Doctors think LXB works on parts of the brain that keep people awake. LXB may quiet those brain parts down at night by reducing their electrical activity, which helps people sleep better. LXB wears off by the morning, so people can wake up normally and feel more alert the next day. LXB has less sodium (which is part of salt) than a medicine called sodium oxybate. Sodium oxybate has been used for narcolepsy for more than 20 years. LXB has several benefits. First, LXB may be healthier than medicines that contain a lot of sodium, such as a high-sodium oxybate. This is because sodium can increase blood pressure and risk of heart disease. Second, LXB can be taken twice each night for narcolepsy, or once or twice each night for idiopathic hypersomnia. This depends on a person’s lifestyle, how well the medicine is working, and side effects. Third, people taking LXB are more able to work and do other activities and have better quality of life. Finally, people taking LXB may lose weight. This can help overweight or obese people. Keywords: cardiovascular, dosing, LXB, hypersomnolence, quality of life, weight loss

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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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The major end-products of dietary fiber fermentation by gut microbiota are the short-chain fatty acids (SCFAs) acetate, propionate, and butyrate, which have been shown to modulate host metabolism via effects on metabolic pathways at different tissue sites. Several studies showed the inhibitory effects of sodium propionate (SP) on nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. We carried out an in vitro model of inflammation on the J774-A1 cell line, by stimulation with lipopolysaccharide (LPS) and H2O2, followed by the pre-treatment with SP at 0.1, 1 mM and 10 mM. To evaluate the effect on acute inflammation and superoxide anion-induced pain, we performed a model of carrageenan (CAR)-induced rat paw inflammation and intraplantar injection of KO2 where rats received SP orally (10, 30, and 100 mg/kg). SP decreased in concentration-dependent-manner the expression of cicloxigenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) following LPS stimulation. SP was able to enhance anti-oxidant enzyme production such as manganese superoxide dismutase (MnSOD) and heme oxygenase-1 (HO-1) following H2O2 stimulation. In in vivo models, SP (30 and 100 mg/kg) reduced paw inflammation and tissue damage after CAR and KO2 injection. Our results demonstrated the anti-inflammatory and anti-oxidant properties of SP; therefore, we propose that SP may be an effective strategy for the treatment of inflammatory diseases.

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Mutations in a voltage-gated sodium channel (SCN1A) result in Dravet Syndrome (DS), a catastrophic childhood epilepsy. Zebrafish with a mutation in scn1Lab recapitulate salient phenotypes associated with DS, including seizures, early fatality, and resistance to antiepileptic drugs. To discover new drug candidates for the treatment of DS, we screened a chemical library of ∼1000 compounds and identified 4 compounds that rescued the behavioral seizure component, including 1 compound (dimethadione) that suppressed associated electrographic seizure activity. Fenfluramine, but not huperzine A, also showed antiepileptic activity in our zebrafish assays. The effectiveness of compounds that block neuronal calcium current (dimethadione) or enhance serotonin signaling (fenfluramine) in our zebrafish model suggests that these may be important therapeutic targets in patients with DS. Over 150 compounds resulting in fatality were also identified. We conclude that the combination of behavioral and electrophysiological assays provide a convenient, sensitive, and rapid basis for phenotype-based drug screening in zebrafish mimicking a genetic form of epilepsy.

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