The Experts below are selected from a list of 1617 Experts worldwide ranked by ideXlab platform
Mary Jeanne Kreek - One of the best experts on this subject based on the ideXlab platform.
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neuroendocrine effects of naltrexone versus Nalmefene in humans
Human Psychopharmacology-clinical and Experimental, 2020Co-Authors: Eduardo R Butelman, Rebecca S Fry, Rachel Kimani, Brian Reed, Mary Jeanne KreekAbstract:Objective Naltrexone and Nalmefene are approved for the treatment of alcohol use disorders, in different countries. Naltrexone is also approved for the treatment for opioid use disorders, most recently in a depot formulation. These compounds target primarily μ(mu)- and κ(kappa)-opioid receptor systems, which are involved in the downstream neurobiological effects of alcohol and in the modulation of neuroendocrine stress systems. The study objective was to compare the neuroendocrine effects of naltrexone and Nalmefene on adrenocorticotropic hormone (ACTH), cortisol, and prolactin, in normal volunteers. Method Adult normal volunteers (n = 11 male and n = 9 female) were studied in a stress-minimized inpatient setting on three consecutive days, after intravenous saline, naltrexone HCl (10 mg), or Nalmefene HCl (10 mg), in fixed order. ACTH, cortisol, and prolactin were analyzed pre-injection and up to 180 min post-injection. Results Naltrexone and Nalmefene caused elevations in ACTH and cortisol compared with saline. Nalmefene had a greater effect on ACTH and cortisol, compared with naltrexone. Both compounds also caused elevations in prolactin in males (females were not examined, due to the influence of menstrual cycle on prolactin). Conclusions This study suggests that both Nalmefene and naltrexone have effects potentially due to κ-partial agonism in humans, as well as antagonist effects at μ-receptors.
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Nalmefene induced elevation in serum prolactin in normal human volunteers partial kappa opioid agonist activity
Neuropsychopharmacology, 2005Co-Authors: Gavin Bart, Jean M. Bidlack, James H Schluger, Lisa Borg, Mary Jeanne KreekAbstract:In humans, mu- and kappa-opioid receptor agonists lower tuberoinfundibular dopamine, which tonically inhibits prolactin release. Serum prolactin is, therefore, a useful biomarker for tuberoinfundibular dopamine. The current study evaluated the unexpected finding that the relative mu- and kappa-opioid receptor selective antagonist Nalmefene increases serum prolactin, indicating possible kappa-opioid receptor agonist activity. In all, 33 healthy human volunteers (14 female) with no history of psychiatric or substance use disorders received placebo, Nalmefene 3 mg, and Nalmefene 10 mg in a double-blind manner. Drugs were administered between 0900 and 1000 on separate days via 2-min intravenous infusion. Serial blood specimens were analyzed for serum levels of prolactin. Additional in vitro studies of Nalmefene binding to cloned human kappa-opioid receptors transfected into Chinese hamster ovary cells were performed. Compared to placebo, both doses of Nalmefene caused significant elevations in serum prolactin (p<0.002 for Nalmefene 3 mg and p<0.0005 for Nalmefene 10 mg). There was no difference in prolactin response between the 3 and 10 mg doses. Binding assays confirmed Nalmefene's affinity at kappa-opioid receptors and antagonism of mu-opioid receptors. [35S]GTPγS binding studies demonstrated that Nalmefene is a full antagonist at mu-opioid receptors and has partial agonist properties at kappa-opioid receptors. Elevations in serum prolactin following Nalmefene are consistent with this partial agonist effect at kappa-opioid receptors. As kappa-opioid receptor activation can lower dopamine in brain regions important to the persistence of alcohol and cocaine dependence, the partial kappa agonist effect of Nalmefene may enhance its therapeutic efficacy in selected addictive diseases.
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Nalmefene Induced Elevation in Serum Prolactin in Normal Human Volunteers: Partial Kappa Opioid Agonist Activity?
Neuropsychopharmacology, 2005Co-Authors: Gavin Bart, Jean M. Bidlack, James H Schluger, Lisa Borg, Mary Jeanne KreekAbstract:In humans, mu- and kappa-opioid receptor agonists lower tuberoinfundibular dopamine, which tonically inhibits prolactin release. Serum prolactin is, therefore, a useful biomarker for tuberoinfundibular dopamine. The current study evaluated the unexpected finding that the relative mu- and kappa-opioid receptor selective antagonist Nalmefene increases serum prolactin, indicating possible kappa-opioid receptor agonist activity. In all, 33 healthy human volunteers (14 female) with no history of psychiatric or substance use disorders received placebo, Nalmefene 3 mg, and Nalmefene 10 mg in a double-blind manner. Drugs were administered between 0900 and 1000 on separate days via 2-min intravenous infusion. Serial blood specimens were analyzed for serum levels of prolactin. Additional in vitro studies of Nalmefene binding to cloned human kappa-opioid receptors transfected into Chinese hamster ovary cells were performed. Compared to placebo, both doses of Nalmefene caused significant elevations in serum prolactin ( p
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Nalmefene causes greater hypothalamic pituitary adrenal axis activation than naloxone in normal volunteers implications for the treatment of alcoholism
Alcoholism: Clinical and Experimental Research, 1998Co-Authors: James H Schluger, Lisa Borg, Margaret Porter, Swapnil Maniar, Mithat Gunduz, Guillaurne Perret, Andrea C King, Mary Jeanne KreekAbstract:Among other actions, opioid antagonists modulate the control endogenous opioids exert on the hypothalamic-pituitary-adrenal (HPA) axis. Naloxone, Nalmefene, and naltrexone are the opioid antagonists approved for use in man and are primarily mu-opioid selective. Naltrexone and Nalmefene have been demonstrated to be useful in the treatment of alcoholism. Compared with naloxone, Nalmefene has a longer half-life, is more potent at the mu-receptor, and has a higher affinity for kappa- and delta-opioid receptors. We conducted an inpatient study comparing the effects of 10 and 30 mg doses of intravenous naloxone and Nalmefene in normal, nonsubstance nor alcohol-abusing, volunteers. Significant increases in ACTH and cortisol were observed after both antagonists, without an apparent dose-response relationship; however, both doses of Nalmefene resulted in greater HPA axis activation than either dose of naloxone (ACTH: p <0.005). These results indicate that kappa- and delta-opioids may play important roles in the regulation of the HPA axis; Nalmefene may be useful as both a probe to explore the HPA axis physiology and as a pharmacotherapeutic agent.
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Use of positron emission tomography to measure the effects of Nalmefene on D1 and D2 dopamine receptors in rat brain
Brain Research, 1997Co-Authors: Ellen M. Unterwald, Hideo Tsukada, Takeharu Kakiuchi, Tsuyoshi Kosugi, Shingo Nishiyama, Mary Jeanne KreekAbstract:Abstract Positron emission tomography (PET) has been used in humans and in non-human primates to image and measure radioligand binding to neuroreceptors. The present study evaluated the feasibility of performing high-resolution PET experiments in a rodent model to measure receptor kinetics. The effects of acute and chronic administration of the opioid antagonist, Nalmefene, on the binding activity of [ 11 C]SCH23390 and [ 11 C] N -methylspiperone at D 1 and D 2 dopamine receptors, respectively, was investigated in the rat. The interaction between central opioid and dopaminergic systems has been the focus of much attention due to their interactive role in mediating reinforcement and locomotor activity. In the present study, adult male Sprague–Dawley rats received either a single injection of 10 mg/kg of Nalmefene or control vehicle solution 1 h prior to the PET scan or were chronically administered 10 mg/kg/day of Nalmefene or vehicle for 7 days by an osmotic minipump. Following acute administration of Nalmefene, the binding potential of [ 11 C]SCH23390 in the striatum was significantly increased. No changes in [ 11 C] N -methylspiperone binding were found. Following chronic Nalmefene administration, no significant change in either [ 11 C]SCH23390 binding potential or [ 11 C] N -methylspiperone binding was detected. These results suggest that Nalmefene administration produces transient changes in the binding potential of D 1 -receptors in the striatum that are normalized after 1 week of steady-state administration.
Antoni Gual - One of the best experts on this subject based on the ideXlab platform.
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who receives Nalmefene and how does it work in the real world a single arm phase iv study of Nalmefene in alcohol dependent outpatients baseline and 1 month results
Clinical Drug Investigation, 2018Co-Authors: Pablo Barrio, Lluisa Ortega, Josep Guardia, Carlos Roncero, Lara Yuguero, Antoni GualAbstract:Alcohol dependence remains a major health problem from both a public health and clinical perspective. Harm reduction strategies have been increasingly recognized as suitable treatment goals. Nalmefene has been recently approved for this precise therapeutic indication after completion of phase III trials. However, more data from routine practice settings are needed in order to obtain evidence with high external validity. The aim of this study was to conduct a single-arm, phase IV study with alcohol-dependent outpatients starting Nalmefene for the first time. An observational, multisite, single-arm, phase IV study was conducted among adult alcohol-dependent outpatients who received Nalmefene for the first time. The study consisted of four visits: baseline, 4 weeks (referred to as 1 month hereafter), 6 and 12 months. At each visit, drinking variables were obtained from the Timeline Followback regarding the previous month. Satisfaction with medication was also assessed for both patients and professionals, with the Medication Satisfaction Questionnaire. A repeated measures mixed model was performed for effectiveness analysis regarding drinking outcomes (reduction in total alcohol consumption and number of heavy drinking days). Regression analyses were performed in order to find predictors of response to Nalmefene. A total of 110 patients were included, with 88 reporting data at the 1-month visit. On average, patients took Nalmefene 68% of the days. The number of heavy drinking days decreased from 13.5 to 6.8 days/month, and total alcohol consumption decreased from 169 to 79 units. For both outcomes, significant reductions at 1 month were found, with no other significant variables reaching significance. Thirty-seven patients were considered medication responders, but given the high presence of low-risk drinkers in our sample, no significant predictors could be found. Satisfaction was globally high for both professionals and patients, and overall Nalmefene was well tolerated, with no serious adverse events reported. The data provided by this phase IV study suggest Nalmefene is an effective, well-tolerated treatment for alcohol dependence in real-world, clinical settings.
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ORIGINAL ARTICLE Efficacy of As-Needed Nalmefene in Alcohol-Dependent Patients with at Least a High Drinking Risk Level: Results from a Subgroup Analysis of Two Randomized Controlled 6-Month Studies
2016Co-Authors: Wim Van Den Brink, Antoni Gual, Lars Torup, Henrijean Aubin, Anna Bladstrom, Karl MannAbstract:Abstract — Aims: The aim of the study was to investigate the efficacy and safety of as-needed use of Nalmefene 18 mg versus placebo in reducing alcohol consumption in patients who did not reduce their alcohol consumption after an initial assessment, i.e. the pooled subgroup of patients with at least a high drinking risk level (men:>60 g/day; women:>40 g/day) at both screening and randomization from the two randomized controlled 6-month studies ESENSE 1 (NCT00811720) and ESENSE 2 (NCT00812461). Methods: Nalmefene 18 mg and placebo were taken on an as-needed basis. All the patients also received a motivational and adherence-enhancing intervention (BRENDA). The co-primary outcomes were number of heavy drinking days (HDDs) and mean total alcohol consumption (g/day) in Month 6 measured using the Timeline Follow-back method. Additionally, data on clinical improvement, liver function and safety were collected throughout the study. Results: The pooled population consisted of 667 patients: placebo n = 332; Nalmefene n = 335. There was a superior effect of Nalmefene compared with placebo in reducing the number of HDDs [treatment difference: −3.2 days (95 % CI: −4.8; −1.6); P < 0.0001] and total alcohol consumption [treatment difference: −14.3 g/day (−20.8; −7.8); P < 0.0001] a
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Nalmefene is effective at reducing alcohol seeking treating alcohol cocaine interactions and reducing alcohol induced histone deacetylases gene expression in blood
British Journal of Pharmacology, 2016Co-Authors: Javier Callejaconde, Victor Echeverryalzate, Elena Gine, Kora Mareen Buhler, Roser Nadal, Rafael Maldonado, Fernando Rodriguez De Fonseca, Antoni Gual, Jose Antonio LopezmorenoAbstract:Background and Purpose The opioid antagonist Nalmefene (selincro®) was approved for alcohol-related disorders by the European Medicines Agency in 2013. However, there have been no studies regarding the effectiveness of Nalmefene when alcohol is used in combination with cocaine. Experimental Approach Using operant alcohol self-administration in Wistar rats and qRT-PCR, we evaluated (i) the dose–response curve for s.c. and p.o. Nalmefene; (ii) the effects of Nalmefene with increasing concentrations of alcohol; (iii) the efficacy of Nalmefene on cocaine-potentiated alcohol responding; and (iv) the gene expression profiles of histone deacetylases (Hdac1–11) in peripheral blood in vivo and in the prefrontal cortex, heart, liver and kidney post mortem. Key Results S.c. (0.01, 0.05, 0.1 mg·kg−1) and p.o. (10, 20, 40 mg·kg−1) Nalmefene dose-dependently reduced alcohol-reinforced responding by up to 50.3%. This effect of Nalmefene was not dependent on alcohol concentration (10, 15, 20%). Cocaine potentiated alcohol responding by approximately 40% and Nalmefene (0.05 mg·kg−1) reversed this effect of cocaine. Alcohol increased Hdac gene expression in blood and Nalmefene prevented the increases in Hdacs 3, 8, 5, 7, 9, 6 and 10. In the other tissues, alcohol and Nalmefene either did not alter the gene expression of Hdacs, as in the prefrontal cortex, or a tissue-Hdac-specific effect was observed. Conclusions and Implications Nalmefene might be effective as a treatment for alcohol-dependent patients who also use cocaine. Also, the expression of Hdacs in peripheral blood might be useful as a biomarker of alcohol use and drug response.
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safety and tolerability of as needed Nalmefene in the treatment of alcohol dependence results from the phase iii clinical programme
Expert Opinion on Drug Safety, 2015Co-Authors: Wim Van Den Brink, Sørensen Per, Antoni Gual, John Strang, Thomas Jensen, Karl MannAbstract:Objective: To investigate safety and tolerability of Nalmefene for reduction of alcohol consumption in alcohol-dependent patients.Methods: Pooled data from three randomized, placebo-controlled studies (two 6-month; one 12-month) of 18 mg Nalmefene (as-needed use) in alcohol-dependent patients looking at the total population (placebo n = 824, Nalmefene n = 1123) and patients with high/very high drinking risk levels at screening and randomization (target population: placebo n = 374, Nalmefene n = 450).Results: In the study, 62.7% of patients on placebo and 74.7% on Nalmefene in the total population had treatment-emergent adverse events (TEAEs). Fourty-seven (5.9%) on placebo and 149 (13.0%) on Nalmefene dropped out due to TEAEs. Thirty-five (4.4%) on placebo and 57 (5.0%) on Nalmefene had serious adverse events. Tolerability and safety were similar in the target population and total population. Most frequent TEAEs were transient, mainly occurring at treatment initiation. There was no difference in tolerabil...
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long term efficacy tolerability and safety of Nalmefene as needed in patients with alcohol dependence a 1 year randomised controlled study
Journal of Psychopharmacology, 2014Co-Authors: Wim Van Den Brink, Sørensen Per, Karl Mann, Lars Torup, Antoni GualAbstract:This study evaluated the long-term efficacy and safety of Nalmefene treatment in reducing alcohol consumption. We randomised (1:3) 675 alcohol-dependent patients ≥ 18 years of age to 52 weeks of as-needed treatment with placebo or Nalmefene 18 mg/day: A total of 112 patients (68%) in the placebo group and 310 (62%) in the Nalmefene group completed the study. At month 6, the co-primary outcome variables showed no statistically-significant differences between the treatment groups; but at month 13, Nalmefene was more effective than placebo, both in the reduction of the number of heavy drinking days (HDDs) (- 1.6 days/month (95% CI - 2.9; - 0.3); p = 0.017) and the reduction of total alcohol consumption (TAC) (- 6.5 g/day last month (95% CI - 12.5; - 0.4); p = 0.036). In a subgroup analysis of patients with high/very high drinking risk levels at screening and at randomisation (the target population), there was a significant effect in favour of Nalmefene on TAC at month 6, and on both HDD and TAC at month 13. Improvements in Clinical Global Impression and liver enzymes were greater with Nalmefene, compared to placebo. Most adverse events were mild or moderate, and transient; adverse events, including those leading to dropout, were more common with Nalmefene. This study provides evidence for the long-term safety and efficacy of Nalmefene as-needed in alcohol-dependent patients whom continue to drink heavily, following a brief intervention.
Karl Mann - One of the best experts on this subject based on the ideXlab platform.
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Nalmefene attenuates neural alcohol cue-reactivity in the ventral striatum and subjective alcohol craving in patients with alcohol use disorder
Psychopharmacology, 2021Co-Authors: Damian Karl, Karl Mann, J. Malte Bumb, Patrick Bach, Christina Dinter, Anne Koopmann, Derik Hermann, Falk Kiefer, Sabine Vollstädt-kleinAbstract:Rationale Alcohol use disorder is a common and devastating mental illness for which satisfactory treatments are still lacking. Nalmefene, as an opioid receptor modulator, could pharmacologically support the reduction of drinking by reducing the (anticipated) rewarding effects of alcohol and expanding the range of treatment options. It has been hypothesized that Nalmefene acts via an indirect modulation of the mesolimbic reward system. So far, only a few imaging findings on the neuronal response to Nalmefene are available. Objectives We tested the effect of a single dose of 18 mg Nalmefene on neuronal cue-reactivity in the ventral and dorsal striatum and subjective craving. Methods Eighteen non-treatment-seeking participants with alcohol use disorder (67% male, M = 50.3 ± 13.9 years) with a current high-risk drinking level ( M = 76.9 ± 52 g of pure alcohol per day) were investigated using a cue-reactivity task during functional magnetic resonance imaging (fMRI) in a double-blind, placebo-controlled, cross-over study/design. In addition, self-reported craving was assessed before and after exposure to alcohol cues. Results An a priori defined region of interest (ROI) analysis of fMRI data from 15 participants revealed that Nalmefene reduced alcohol cue-reactivity in the ventral, but not the dorsal striatum. Additionally, the subjective craving was significantly reduced after the cue-reactivity task under Nalmefene compared to placebo. Conclusion In the present study, reduced craving and cue-reactivity to alcohol stimuli in the ventral striatum by Nalmefene indicates a potential anti-craving effect of this drug via attenuation of neural alcohol cue-reactivity.
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the effects of Nalmefene on emotion processing in alcohol use disorder a randomized controlled fmri study
European Neuropsychopharmacology, 2019Co-Authors: Sabine Vollstadtklein, Karl Mann, Damian Karl, Christina Dinter, Anne Koopmann, Derik Hermann, Malte J Bumb, Amelie Otto, Falk KieferAbstract:Nalmefene is a µ- and δ-opioid receptor antagonist and a partial κ-opioid receptor agonist. The drug is suggested to reduce the craving for, and the consumption of alcohol effectively, also alleviating anxiety and anhedonia. The present fMRI study is the first to investigate the processing of emotions as a possible mechanism of action of Nalmefene in humans. Fifteen non-treatment-seeking participants suffering from alcohol use disorder (AUD) (24-66 years; 5 females) finished this randomized, placebo controlled, double blind study. Following a cross over design, participants received either a single dose Nalmefene or a placebo, with an interval of one week between sessions. Using fMRI, we investigated neural reactivity during the presentation of emotional faces picture sets. Additionally, we performed a visual dot-probe task to detect Nalmefene's effects on attentional bias. We detected an increase in the response to emotional faces in the supramarginal gyrus, the angular gyrus as well as the putamen in the Nalmefene vs. placebo condition. However, contradictory to our initial hypotheses, amygdala activation was not altered significantly in the placebo condition - a limitation, which might be associated with a lack of activation in the placebo condition maybe due to the small sample size. Attentional bias analyses revealed an interaction effect by trend, which was driven by a significant effect in a sub-analysis showing increased attentional shift towards happy compared to fearful facial expressions under Nalmefene. Nalmefene increased brain activation in areas responsible for empathy, social cognition and behavior, which might help alleviating the reinforcing properties of alcohol.
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ORIGINAL ARTICLE Efficacy of As-Needed Nalmefene in Alcohol-Dependent Patients with at Least a High Drinking Risk Level: Results from a Subgroup Analysis of Two Randomized Controlled 6-Month Studies
2016Co-Authors: Wim Van Den Brink, Antoni Gual, Lars Torup, Henrijean Aubin, Anna Bladstrom, Karl MannAbstract:Abstract — Aims: The aim of the study was to investigate the efficacy and safety of as-needed use of Nalmefene 18 mg versus placebo in reducing alcohol consumption in patients who did not reduce their alcohol consumption after an initial assessment, i.e. the pooled subgroup of patients with at least a high drinking risk level (men:>60 g/day; women:>40 g/day) at both screening and randomization from the two randomized controlled 6-month studies ESENSE 1 (NCT00811720) and ESENSE 2 (NCT00812461). Methods: Nalmefene 18 mg and placebo were taken on an as-needed basis. All the patients also received a motivational and adherence-enhancing intervention (BRENDA). The co-primary outcomes were number of heavy drinking days (HDDs) and mean total alcohol consumption (g/day) in Month 6 measured using the Timeline Follow-back method. Additionally, data on clinical improvement, liver function and safety were collected throughout the study. Results: The pooled population consisted of 667 patients: placebo n = 332; Nalmefene n = 335. There was a superior effect of Nalmefene compared with placebo in reducing the number of HDDs [treatment difference: −3.2 days (95 % CI: −4.8; −1.6); P < 0.0001] and total alcohol consumption [treatment difference: −14.3 g/day (−20.8; −7.8); P < 0.0001] a
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safety and tolerability of as needed Nalmefene in the treatment of alcohol dependence results from the phase iii clinical programme
Expert Opinion on Drug Safety, 2015Co-Authors: Wim Van Den Brink, Sørensen Per, Antoni Gual, John Strang, Thomas Jensen, Karl MannAbstract:Objective: To investigate safety and tolerability of Nalmefene for reduction of alcohol consumption in alcohol-dependent patients.Methods: Pooled data from three randomized, placebo-controlled studies (two 6-month; one 12-month) of 18 mg Nalmefene (as-needed use) in alcohol-dependent patients looking at the total population (placebo n = 824, Nalmefene n = 1123) and patients with high/very high drinking risk levels at screening and randomization (target population: placebo n = 374, Nalmefene n = 450).Results: In the study, 62.7% of patients on placebo and 74.7% on Nalmefene in the total population had treatment-emergent adverse events (TEAEs). Fourty-seven (5.9%) on placebo and 149 (13.0%) on Nalmefene dropped out due to TEAEs. Thirty-five (4.4%) on placebo and 57 (5.0%) on Nalmefene had serious adverse events. Tolerability and safety were similar in the target population and total population. Most frequent TEAEs were transient, mainly occurring at treatment initiation. There was no difference in tolerabil...
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Alcohol Dependence and Alcoholic Liver Disease
European Medical Journal, 2015Co-Authors: Karl Mann, Sebastian MuellerAbstract:Alcohol dependence is a disabling condition that has a high prevalence, but in Europe only a small fraction of the people diagnosed with alcohol abuse and dependence are treated, representing the widest treatment gap, as compared with other mental disorders. Early diagnosis and monitoring of alcoholic liver disease (ALD) is still insufficiently solved. Although ALD is the most common cause for liver disease in the Western world, it largely remains underestimated and underdiagnosed for many reasons. The recent introduction of non-invasive elastographic techniques such as transient elastography (TE) has significantly improved the early diagnosis of alcoholic liver cirrhosis (ALC). As demonstrated in the literature, inflammation-associated liver stiffness (LS) rapidly decreases during alcohol detoxification, and is also directly correlated to change in LS in both abstinent and relapsing patients. Newly published data show that LS could be used to monitor and validate hepatoprotective effects during Nalmefene usage. Nalmefene is an opioid system modulator that diminishes the reinforcing effects of alcohol, helping the patient to reduce drinking. Three randomised, multicentre, double-blind, placebo-controlled, parallelgroup Phase III studies were designed to assess the efficacy and safety of Nalmefene in reducing alcohol consumption. Patients with a high or very high drinking risk level (DRL) at baseline and randomisation show a clinically significant effect from Nalmefene treatment, which is generally well tolerated. Moreover, reduced alcohol consumption supported by Nalmefene in combination with psychosocial support may indeed help to reduce the alcohol-related burden and the large treatment gap
Juergen Rehm - One of the best experts on this subject based on the ideXlab platform.
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A Trial-Based Predictive Microsimulation Assessing the Public Health ă Benefits of Nalmefene and Psychosocial Support for the Reduction of ă Alcohol Consumption in Alcohol Dependence
Applied Health Economics and Health Policy, 2016Co-Authors: Philippe Laramee, Olivier Cristeau, Nora Rahhali, Ylana Chalem, Clement Francois, Mondher Toumi, Aurélie Millier, Samuel Aballea, Juergen RehmAbstract:Background Alcohol dependence causes considerable harm to patients. ă Treatment with Nalmefene, aiming to reduce consumption rather than ă maintain complete abstinence, has been licensed based on trials ă demonstrating a reduction in total alcohol consumption and heavy ă drinking days. Relating these trial outcomes to harmful events avoided ă is important to demonstrate the clinical relevance of Nalmefene ă treatment. ă Methods A predictive microsimulation model was developed to compare ă Nalmefene plus brief psychosocial intervention (BRENDA) versus placebo ă plus BRENDA for the treatment of patients with alcohol dependence and a ă high or very high drinking risk level based on three pooled clinical ă trials. The model simulated patterns and level of alcohol consumption, ă day-by-day, for 12 months, to estimate the occurrence of ă alcohol-attributable diseases, injuries and deaths; assessing the ă clinical relevance of reducing alcohol consumption with treatment. ă Results The microsimulation model predicted that, in a cohort of 100,000 ă patients, 971 (95 % confidence interval [CI] 904-1038) ă alcohol-attributable diseases and injuries and 133 (95 % CI 117-150) ă deaths would be avoided with Nalmefene versus placebo. This level of ă benefit has been considered clinically relevant by the European ă Medicines Agency. ă Conclusions This microsimulation model supports the clinical relevance ă of the reduction in alcohol consumption, and has estimated the extent of ă the public health benefit of treatment with Nalmefene in patients with ă alcohol dependence and a high or very high drinking risk level.
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a trial based predictive microsimulation assessing the public health benefits of Nalmefene and psychosocial support for the reduction of alcohol consumption in alcohol dependence
Applied Health Economics and Health Policy, 2016Co-Authors: Philippe Laramee, Olivier Cristeau, Nora Rahhali, Ylana Chalem, Juergen Rehm, Clement Francois, Mondher Toumi, Aurélie Millier, Samuel AballeaAbstract:Background Alcohol dependence causes considerable harm to patients. Treatment with Nalmefene, aiming to reduce consumption rather than maintain complete abstinence, has been licensed based on trials demonstrating a reduction in total alcohol consumption and heavy drinking days. Relating these trial outcomes to harmful events avoided is important to demonstrate the clinical relevance of Nalmefene treatment.
Lars Torup - One of the best experts on this subject based on the ideXlab platform.
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ORIGINAL ARTICLE Efficacy of As-Needed Nalmefene in Alcohol-Dependent Patients with at Least a High Drinking Risk Level: Results from a Subgroup Analysis of Two Randomized Controlled 6-Month Studies
2016Co-Authors: Wim Van Den Brink, Antoni Gual, Lars Torup, Henrijean Aubin, Anna Bladstrom, Karl MannAbstract:Abstract — Aims: The aim of the study was to investigate the efficacy and safety of as-needed use of Nalmefene 18 mg versus placebo in reducing alcohol consumption in patients who did not reduce their alcohol consumption after an initial assessment, i.e. the pooled subgroup of patients with at least a high drinking risk level (men:>60 g/day; women:>40 g/day) at both screening and randomization from the two randomized controlled 6-month studies ESENSE 1 (NCT00811720) and ESENSE 2 (NCT00812461). Methods: Nalmefene 18 mg and placebo were taken on an as-needed basis. All the patients also received a motivational and adherence-enhancing intervention (BRENDA). The co-primary outcomes were number of heavy drinking days (HDDs) and mean total alcohol consumption (g/day) in Month 6 measured using the Timeline Follow-back method. Additionally, data on clinical improvement, liver function and safety were collected throughout the study. Results: The pooled population consisted of 667 patients: placebo n = 332; Nalmefene n = 335. There was a superior effect of Nalmefene compared with placebo in reducing the number of HDDs [treatment difference: −3.2 days (95 % CI: −4.8; −1.6); P < 0.0001] and total alcohol consumption [treatment difference: −14.3 g/day (−20.8; −7.8); P < 0.0001] a
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p 81secondary benefits of alcohol reduction with Nalmefene
Alcohol and Alcoholism, 2015Co-Authors: Henrijean Aubin, Clement Francois, Lars Torup, Didier Meulien, S Ting, Amandine LuquiensAbstract:The opioid system modulator Nalmefene reduce average daily total alcohol consumption, number of heavy drinking days, and improve liver function and clinical status in alcohol-dependent patients. We investigated the effect of alcohol reduction with Nalmefene 18 mg on alcohol dependence features, drinking consequences, and mood in two 6-month randomized, double-blind, placebo-controlled, studies (NCT00811720; NCT00812461) in alcohol-dependent patients. …
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clinical relevance of as needed treatment with Nalmefene in alcohol dependent patients
European Addiction Research, 2015Co-Authors: Henrijean Aubin, Clement Francois, Lars Torup, Jens Reimer, David J Nutt, Bladstrom Anna, Jonathan ChickAbstract:Nalmefene is the first drug approved for reduction of alcohol consumption. The aim of this study was to evaluate the clinical relevance of treatment with Nalmefene in alcohol-dependent patients with a high drinking risk level from two randomised placebo-controlled 6-month studies (NCT00811720 and NCT00812461). Response criteria were based on alcohol consumption, Clinical Global Impression, and Short Form Health Survey mental component summary scores at month 6, analysed using logistic regression. The proportion of responders was higher in the Nalmefene group than in the placebo group with odds ratios significantly in favour of Nalmefene for all responder criteria; numbers-needed-to-treat ranged from 6 to 10. Significant differences from placebo in clinician-rated and patient-reported outcomes, and liver enzymes further supported the clinical relevance of the treatment effect. In conclusion, this study supports the clinical relevance of Nalmefene treatment in patients with alcohol dependence. Nalmefene may help to reduce the alcohol-related burden and the large treatment gap, with currently less than 10% of alcohol-dependent patients in Europe receiving treatment.
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long term efficacy tolerability and safety of Nalmefene as needed in patients with alcohol dependence a 1 year randomised controlled study
Journal of Psychopharmacology, 2014Co-Authors: Wim Van Den Brink, Sørensen Per, Karl Mann, Lars Torup, Antoni GualAbstract:This study evaluated the long-term efficacy and safety of Nalmefene treatment in reducing alcohol consumption. We randomised (1:3) 675 alcohol-dependent patients ≥ 18 years of age to 52 weeks of as-needed treatment with placebo or Nalmefene 18 mg/day: A total of 112 patients (68%) in the placebo group and 310 (62%) in the Nalmefene group completed the study. At month 6, the co-primary outcome variables showed no statistically-significant differences between the treatment groups; but at month 13, Nalmefene was more effective than placebo, both in the reduction of the number of heavy drinking days (HDDs) (- 1.6 days/month (95% CI - 2.9; - 0.3); p = 0.017) and the reduction of total alcohol consumption (TAC) (- 6.5 g/day last month (95% CI - 12.5; - 0.4); p = 0.036). In a subgroup analysis of patients with high/very high drinking risk levels at screening and at randomisation (the target population), there was a significant effect in favour of Nalmefene on TAC at month 6, and on both HDD and TAC at month 13. Improvements in Clinical Global Impression and liver enzymes were greater with Nalmefene, compared to placebo. Most adverse events were mild or moderate, and transient; adverse events, including those leading to dropout, were more common with Nalmefene. This study provides evidence for the long-term safety and efficacy of Nalmefene as-needed in alcohol-dependent patients whom continue to drink heavily, following a brief intervention.
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epa 0255 clinical relevance of as needed treatment with Nalmefene in alcohol dependent patients
European Psychiatry, 2014Co-Authors: Henrijean Aubin, Clement Francois, Lars Torup, Jens Reimer, David J Nutt, Jonathan ChickAbstract:Introduction The opioid system modulator Nalmefeneis the first pharmacological therapy approved in the European Union for reduction of alcohol consumption. Objectives To evaluate the clinical relevance of the reduction of alcohol consumption in patients with at least high drinking risk level at screening and randomisation from the two, identically designed, randomised controlled 6-month studies ESENSE1 (NCT00811720) and ESENSE2 (NCT00812461) of Nalmefene versus placebo. Methods Study medication was taken as-needed. All patients received a motivational and adherence-enhancing intervention (BRENDA). Response criteria were based on alcohol consumption at month 6 and Clinical Global Impression – Severity of Illness/Improvement (CGI-S/I), Short Form Health Survey version 2 (SF-36) mental component summary(MCS) scores at week 24. Clinical relevance was also studied using the Drinker Inventory of Consequences (DrInC), Alcohol Dependence Scale (ADS), and liver function variables. Results Pooled study population: 667 patients (placebo N=332; Nalmefene N=335). The proportion of responders was higher in the Nalmefene group than in the placebo group with odds ratios for response consistently significantly (p Conclusions In view of the immense alcohol-related burden to society, the harm to the individual and the large treatment gap partly due to a reluctance to engage in abstinence, the effect of Nalmefene is clearly clinically relevant.
