Aims: This 12-week, open-label, primary care study (NCT02195817) evaluated the efficacy and safety of nalmefene, taken as needed, to reduce alcohol consumption in adults with a diagnosis of alcohol dependence and drinking at least at high drinking risk levels (DRL, > 60 g/day for men, > 40 g/day for women). Methods: Following the Screening Visit, patients recorded their daily alcohol consumption for 2 weeks. Patients were then categorised by their self-reported drinking levels; those who maintained at least a high DRL in the 2-week period were included in Cohort-A, and those who reduced their alcohol consumption below high DRL were included in Cohort-B. Cohort-A received simple psychosocial interventions and were supplied with nalmefene 18 mg to be taken on days when they perceived a risk of drinking alcohol. Patients in Cohort-B received a simple psychosocial intervention and were treated per normal practice. Results: Of the 378 enrolled patients, 330 were included in Cohort-A and 48 in Cohort-B. For patients in Cohort-A, the mean change from screening to Week-12 in the number of heavy drinking days/month was –13.1 days/month (95% CI –14.4 to –11.9, p < 0.0001). Overall, 55% of patients reduced their DRL by ≥2 risk levels and 44% of patients reduced to a low DRL. The most common adverse events were nausea (18.3%) and dizziness (17.7%). Patients in Cohort-B maintained their lower level alcohol consumption at the 12-week follow-up. Conclusions: Patients with alcohol dependence treated in primary care with nalmefene, taken as needed, in conjunction with simple psychosocial support, significantly reduced their alcohol consumption. Treatment was well tolerated.

ObjectivesThe objective of this study was to evaluate the long‐term safety and tolerability of flexible‐dose brexpiprazole adjunct to antidepressant treatment (ADT) in elderly patients with major depressive disorder (MDD).MethodsElderly patients (≥65 years) with MDD and inadequate response to ≥1 ADT during the current episode were recruited to a 26‐week, interventional, open‐label study (NCT02400346) at outpatient centers in the USA and Europe. All patients received brexpiprazole 1 to 3 mg/day adjunct to their current ADT. Safety outcomes included adverse events (AEs), movement disorder scales, and standard safety assessments (vital signs, laboratory safety parameters, physical examination, electrocardiograms). Exploratory efficacy outcomes included the Montgomery–Åsberg Depression Rating Scale (MADRS), Clinical Global Impressions‐Severity of Illness (CGI‐S), and Social Adaptation Self‐Evaluation Scale (SASS).ResultsOf the 132 treated patients, 88 (66.7%) completed the study and 44 (33.3%) withdrew, including 24 who withdrew because of AEs (18.2%). Overall, 102 patients (77.3%) experienced ≥1 treatment‐emergent AE (TEAE), which were mostly mild or moderate in severity. Treatment‐emergent AEs with the highest incidence were fatigue (15.2%) and restlessness (12.9%). The most common TEAE leading to withdrawal was fatigue (3.0%). No consistent clinically relevant findings were seen with regard to movement disorder scales or standard safety assessments. Mean (standard error) efficacy score changes from baseline to week 26 were: MADRS total, −14.5 (0.9); CGI‐S, −1.8 (0.1); and SASS, 3.2 (0.5).ConclusionsLong‐term (26‐week) treatment with adjunctive brexpiprazole was generally well tolerated in elderly patients with MDD and inadequate response to prior ADT. Improvements were observed in depressive symptoms and social functioning.

Aims This open-label study in patients with alcohol dependence and evidence of elevated liver stiffness and/or hepatic steatosis was designed to explore the efficacy of nalmefene (18 mg) in reducing alcohol consumption and its subsequent effects on a variety of clinically relevant liver parameters. Methods Adult patients with a diagnosis of alcohol dependence and evidence of elevated liver stiffness and/or hepatic steatosis (liver stiffness >6 kPa or controlled attenuation parameter (CAP) >215 dB/m as measured by transient elastography) were recruited at two study sites in Germany. During the 12-week treatment period, patients were instructed to take nalmefene each day they perceived a risk of drinking alcohol. Results All 45 enrolled patients took at least one dose of nalmefene and 39 completed the study. After 12 weeks of study treatment with nalmefene patients showed a reduction in alcohol consumption of −13.5 days/month heavy drinking days and −45.8 g/day total alcohol consumption. Most liver parameters showed modest changes at Week 12; there was a 13% decrease in liver stiffness and 10% reduction in CAP values. Results indicated non-significant negative associations between alcohol consumption and liver stiffness and/or CAP over this 12-week study. Nalmefene was generally well tolerated, and most adverse events were mild or moderate, the most frequent being dizziness. Conclusions Patients treated with nalmefene for 12 weeks had reductions in alcohol consumption by ~50% relative to baseline and showed trends to improvement in liver stiffness and CAP.

Objectives Reports showed that decreased NAD+ bioavailability was believed to disturb metabolism and cause certain disease conditions in aging animal models. While preclinical evidence suggests β-nicotinamide mononucleotide (NMN), as a key NAD+ intermediate, has shown great potential to enhance NAD+ biosynthesis and ameliorate effects of aging in animal models. The bioavailability of NMN was not satisfying when administrated alone. Methods In this study, several NMN compound formulas, combined with other active ingredients, were used in the wild-type zebrafish model to investigate the NAD+ level enhancement and anti-aging effects. Results Remarkably, administered NMN with astaxanthin and blood orange (NOA) was quickly utilized to synthesize NAD+ in zebrafishes and was superior to nicotinamide riboside (NR), NR with astaxanthin and blood orange(ROA), NMN with other active ingredients including pterostilbene (NOP) and roxburgh rose (NOR) with no obvious toxic effects demonstrated. Furthermore, formula NOA could effectively resist fatigue, promote physical activity, regulate sleep, and improve skin status, indicating the mitigation of age-associated physiological decline in zebrafish. Consistent with these phenotypes, NOA upregulated gene expression that could exert regulatory effects on sleep and skin status and raised ATP synthesis. Conclusions These effects of the formula NOA in the zebrafish model demonstrated its preventive and therapeutic potential as an effective anti-aging intervention to improve human health. Funding Sources H&H Group

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