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JAMA Nov 2023Alcohol use disorder affects more than 28.3 million people in the United States and is associated with increased rates of morbidity and mortality. (Comparative Study)
Comparative Study Meta-Analysis
IMPORTANCE
Alcohol use disorder affects more than 28.3 million people in the United States and is associated with increased rates of morbidity and mortality.
OBJECTIVE
To compare efficacy and comparative efficacy of therapies for alcohol use disorder.
DATA SOURCES
PubMed, the Cochrane Library, the Cochrane Central Trials Registry, PsycINFO, CINAHL, and EMBASE were searched from November 2012 to September 9, 2022 Literature was subsequently systematically monitored to identify relevant articles up to August 14, 2023, and the PubMed search was updated on August 14, 2023.
STUDY SELECTION
For efficacy outcomes, randomized clinical trials of at least 12 weeks' duration were included. For adverse effects, randomized clinical trials and prospective cohort studies that compared drug therapies and reported health outcomes or harms were included.
DATA EXTRACTION AND SYNTHESIS
Two reviewers evaluated each study, assessed risk of bias, and graded strength of evidence. Meta-analyses used random-effects models. Numbers needed to treat were calculated for medications with at least moderate strength of evidence for benefit.
MAIN OUTCOMES AND MEASURES
The primary outcome was alcohol consumption. Secondary outcomes were motor vehicle crashes, injuries, quality of life, function, mortality, and harms.
RESULTS
Data from 118 clinical trials and 20 976 participants were included. The numbers needed to treat to prevent 1 person from returning to any drinking were 11 (95% CI, 1-32) for acamprosate and 18 (95% CI, 4-32) for oral naltrexone at a dose of 50 mg/d. Compared with placebo, oral naltrexone (50 mg/d) was associated with lower rates of return to heavy drinking, with a number needed to treat of 11 (95% CI, 5-41). Injectable naltrexone was associated with fewer drinking days over the 30-day treatment period (weighted mean difference, -4.99 days; 95% CI, -9.49 to -0.49 days) Adverse effects included higher gastrointestinal distress for acamprosate (diarrhea: risk ratio, 1.58; 95% CI, 1.27-1.97) and naltrexone (nausea: risk ratio, 1.73; 95% CI, 1.51-1.98; vomiting: risk ratio, 1.53; 95% CI, 1.23-1.91) compared with placebo.
CONCLUSIONS AND RELEVANCE
In conjunction with psychosocial interventions, these findings support the use of oral naltrexone at 50 mg/d and acamprosate as first-line pharmacotherapies for alcohol use disorder.
Topics: Humans; Acamprosate; Alcohol Drinking; Alcoholism; Drug-Related Side Effects and Adverse Reactions; Naltrexone; Prospective Studies; Quality of Life; United States; Alcohol Deterrents; Psychosocial Intervention
PubMed: 37934220
DOI: 10.1001/jama.2023.19761 -
Brain Sciences Aug 2023(1) Background: The treatment of substance addiction is challenging and has persisted for decades, with only a few therapeutic options. Although there are some... (Review)
Review
(1) Background: The treatment of substance addiction is challenging and has persisted for decades, with only a few therapeutic options. Although there are some recommendations for specific treatments for Alcohol Use Disorder (AUD), there is no specific medication used to treat alcohol cravings, which could benefit millions of patients that are suffering from alcoholism. Cravings, or the urge to use drugs, refer to the desire to experience the effects of a previously experienced psychoactive substance. (2) Methods: We included original studies of alcohol abuse or dependence extracted from a controlled, blind, pharmacological treatment study which presented measures and outcomes related to alcohol cravings. (3) Results: Specific drugs used for the treatment of alcoholism, such as Naltrexone and Acamprosate, have had the best results in relieving craving symptoms, as well as promoting abstinence. Baclofen and anticonvulsants such as Gabapentin and Topiramate have shown good results in promoting abstinence and the cessation of cravings. (4) Conclusions: Specific drugs used for the treatment of alcoholism to obtain the best results can be considered the gold standard for promoting abstinence and relieving cravings. Anticonvulsants and Baclofen also had good results, with these medications being considered as second-line ones. Varenicline is an option for alcohol dependents who also concomitantly ingest tobacco.
PubMed: 37626562
DOI: 10.3390/brainsci13081206 -
Cureus Apr 2024Background Alcohol use disorder (AUD) is one of the most common substance use disorders globally. It is a chronic mental illness characterized by frequent...
Background Alcohol use disorder (AUD) is one of the most common substance use disorders globally. It is a chronic mental illness characterized by frequent relapses. Hence, preventing relapse is one of the most important aspects of the management of patients with AUD. Aims This study aimed to compare the role of acamprosate and baclofen as anti-craving agents in patients diagnosed with AUD. Settings and design This was a 12-week interventional follow-up study conducted in the Department of Psychiatry of S N Medical College, a tertiary care teaching hospital in Agra, Uttar Pradesh, India. Methods and materials Patients with AUD were enrolled in the study. Following medical management of alcohol withdrawal symptoms, patients were alternately assigned to receive either acamprosate or baclofen and were then followed up for 12 weeks. Measures to compare the effectiveness of the two medications were craving as measured using the Penn Alcohol Craving Scale (PACS), days to first alcohol consumption, days to relapse, number of drinks consumed at one occasion, number of patients who completed the study, and number of patients who remained abstinent throughout the duration of the study. Descriptive statistics were used to present the data while unpaired t-test and Fisher's exact test were used to compare the two groups. Results A total of 63 patients were enrolled in the study. Following medical management of alcohol withdrawal symptoms for one week, 50 (79.37%) patients were retained in the study. Hence, these 50 patients were assigned to treatment with either acamprosate or baclofen alternately in a 1:1 ratio. Only 32 (64%) of the patients who were started on these medications completed the study and were available for analysis at the end of 12 weeks. Acamprosate-treated patients were found to have less severe cravings (p < 0.01) for alcohol at the end of the study and also had consumed less number of drinks on a single occasion (p < 0.05). For other variables being considered in the study, namely, days to first alcohol consumption, days to relapse to previous drinking pattern, number of patients who dropped from the study versus those who completed the study, and those who were abstinent versus those who relapsed, no statistically significant difference was noted. Conclusion Acamprosate-treated patients had significantly lesser cravings for alcohol and consumed a lesser number of drinks on one occasion compared to baclofen-treated patients in this 12-week study.
PubMed: 38741835
DOI: 10.7759/cureus.58174 -
Scientific Reports Oct 2023Alcohol misuse accounts for a sizeable proportion of the global burden of disease, and Campral (acamprosate; calcium-bis-(N-acetylhomotaurinate)) is widely used as...
Alcohol misuse accounts for a sizeable proportion of the global burden of disease, and Campral (acamprosate; calcium-bis-(N-acetylhomotaurinate)) is widely used as relapse prevention therapy. The mechanism underlying its effect has in some studies been attributed to the calcium moiety and not to the N-acetylhomotaurine part of the compound. We recently suggested that the dopamine elevating effect of acamprosate is mediated both by N-acetylhomotaurine and calcium in a glycine receptor dependent manner. Here we aimed to explore, by means of in vivo microdialysis, if our previous study using local administration was functionally relevant and if systemic administration of the sodium salt of N-acetylhomotaurine (sodium acamprosate; 200 mg/kg, i.p.) enhanced the effects of calcium chloride (CaCl; 73.5 mg/kg, i.p.) on nucleus accumbens (nAc) dopamine and/or taurine levels in male Wistar rats. In addition, we investigated the impact of regular acamprosate and the combination of CaCl and N-acetylhomotaurine on the alcohol deprivation effect (ADE). Finally, we assessed if N-acetylhomotaurine potentiates the ethanol-intake reducing effect of CaCl in a two-bottle choice voluntary ethanol consumption model followed by an ADE paradigm. Systemic administration of regular acamprosate, sodium acamprosate and CaCl all trended to increase nAc dopamine whereas the combination of CaCl and sodium acamprosate produced a significant increase. Sodium acamprosate elevated extracellular taurine levels without additional effects of CaCl. Ethanol intake was significantly reduced by systemic administration of CaCl without additional effects of the combination of CaCl and sodium acamprosate. Both acamprosate and CaCl combined with sodium acamprosate blocked the ADE following acute treatment. The data presented suggest that CaCl and N-acetylhomotaurine act in concert on a neurochemical level, but calcium appears to have the predominant effect on ethanol intake.
Topics: Rats; Male; Animals; Acamprosate; Ethanol; Rats, Wistar; Calcium; Calcium Chloride; Dopamine; Taurine; Sodium
PubMed: 37857829
DOI: 10.1038/s41598-023-45167-3 -
Journal of General Internal Medicine Nov 2023Alcohol use disorder (AUD) is the most prevalent substance use disorder, but evidence-based medications to treat AUD (MAUD), including naltrexone and acamprosate, are...
BACKGROUND
Alcohol use disorder (AUD) is the most prevalent substance use disorder, but evidence-based medications to treat AUD (MAUD), including naltrexone and acamprosate, are substantially underutilized. Hospitalization provides an opportunity to start MAUD for patients who may not otherwise seek treatment. Addiction consultation services (ACSs) have been increasingly utilized to ensure appropriate treatment. There is little research examining the effect of an ACS on health outcomes among patients with AUD.
OBJECTIVE
To determine the association between an ACS consultation and provision of MAUD during admission and MAUD at discharge among admissions with AUD.
DESIGN
Retrospective study comparing admissions which received an ACS consult and propensity score-matched historical control admissions. Subjects A total of 215 admissions with a primary or secondary diagnosis of AUD who received an ACS consult and 215 matched historical control admissions. Intervention ACS consultation from a multidisciplinary team offering withdrawal management, substance use disorder treatment, patient-centered counseling, discharge planning, and linkage to outpatient care for patients with substance use disorders, including AUD. Main Measures Primary outcomes were initiation of new MAUD during admission and new MAUD at discharge. Secondary outcomes were patient-directed discharge, time to 7- and 30-day readmission, and time to 7- and 30-day post-discharge ER visit. Key Results Among 430 admissions with AUD, those that received an ACS consultation were significantly more likely to receive new inpatient MAUD (33.0% vs 0.9%; OR 52.5 [CI 12.6-218.6]) and significantly more likely to receive new MAUD at discharge (41.4% vs 1.9%; OR 37.3 [13.3-104.6]), compared with historical controls. ACS was not significantly associated with patient-directed discharge, time to readmission, or time to post-discharge ER visit.
CONCLUSIONS
ACS was associated with a large increase in provision of new inpatient MAUD and new MAUD at discharge when compared to propensity-matched historical controls.
Topics: Humans; Alcoholism; Inpatients; Patient Discharge; Retrospective Studies; Aftercare; Substance-Related Disorders; Referral and Consultation
PubMed: 37100986
DOI: 10.1007/s11606-023-08202-7 -
The Australian and New Zealand Journal... Feb 2024Alcohol use disorders confer a significant burden of disease and economic cost worldwide. However, the utilisation of pharmacotherapies to manage alcohol use disorder is... (Review)
Review
OBJECTIVE
Alcohol use disorders confer a significant burden of disease and economic cost worldwide. However, the utilisation of pharmacotherapies to manage alcohol use disorder is poor. We aimed to conduct a systematic review of economic evaluation studies of alcohol use disorder pharmacotherapies.
METHODS
A search was conducted in Embase, Medline, CINAHL, PsychINFO and EconLit (August 2019, updated September 2022). Full economic evaluations using pharmacotherapy to treat alcohol use disorders were included. Included studies were stratified by medication and summarised descriptively. The Consensus on Health Economic Criteria list was used to assess the methodological quality.
RESULTS
A total of 1139 studies were retrieved, of which 15 met the inclusion criteria. All studies were conducted in high-income countries. Four studies analysed nalmefene, four studies assessed acamprosate, three for naltrexone and four for stand-alone and/or combinations of naltrexone and acamprosate. There were 21 interventions synthesised from 15 studies as some studies evaluated multiple interventions and comparators. More than half of the included studies (73%) reported pharmacotherapy as dominant (less costly and more effective than comparators). From healthcare payer perspectives, five studies found that pharmacotherapy added to psychosocial support was dominant or cost-effective, accruing additional benefits at a higher cost but under accepted willingness to pay thresholds. Three analyses from a societal perspective found pharmacotherapy added to psychosocial support was a dominant or cost-effective strategy. Quality scores ranged from 63% to 95%.
CONCLUSION
Pharmacotherapy added to psychosocial support was cost-effective from both healthcare and societal perspectives, emphasising an increased role for pharmacotherapy to reduce the burden of alcohol use disorders.
Topics: Humans; Alcoholism; Acamprosate; Cost-Benefit Analysis; Naltrexone; Alcohol Drinking; Ethanol
PubMed: 37822267
DOI: 10.1177/00048674231201541 -
Addiction Science & Clinical Practice Jun 2024The 15-method is a targeted screening and treatment approach for alcohol problems in primary care. The 15-method used in primary care has proven as effective as... (Randomized Controlled Trial)
Randomized Controlled Trial
The identification and treatment of alcohol problems in primary care (iTAPP) study: protocol for a stepped wedge cluster randomized control trial testing the 15-method in a primary care setting.
BACKGROUND
The 15-method is a targeted screening and treatment approach for alcohol problems in primary care. The 15-method used in primary care has proven as effective as specialized treatment for mild to moderate alcohol dependence in Sweden. A feasibility study of the 15-method in Danish primary care found the method acceptable and feasible.
AIMS
To evaluate the effectiveness of the 15-method in a Danish primary care setting in (1) lowering the proportion of patients exceeding the Danish low-risk alcohol consumption limit of ten standard units per week and a maximum of four standard units on a single day for men and women, and (2) increasing the likelihood of alcohol use being addressed during a consultation in general practice. Further, the rate of prescribed pharmacological treatment for alcohol problems (Disulfiram, Naltrexone, Acamprosate, and Nalmefene) will be measured along with the use of the biomarkers Alanine Transaminase and Gamma-Glutamyl Transferase.
METHODS
Stepped wedge cluster randomized controlled trial in sixteen general practices in the Region of Southern Denmark. Following a three-month baseline, the practices are randomly assigned to launch dates in one of four clusters. General practitioners and nurses receive three hours of training in the 15-method before launch. Patient questionnaires will collect data on alcohol consumption levels among patients affiliated with the practices. The healthcare professionals will register consultations in which alcohol is addressed in their patient filing system. Pharmacological treatment rates and the use of biomarkers will be collected through Danish national registries. The study follows the Medical Research Council's guidelines for developing and evaluating complex interventions.
DISCUSSION
From the patient's perspective, the 15-method may help identify alcohol-related problems at an earlier stage with flexible treatment offers in a familiar setting. For healthcare professionals, it addresses a traditionally challenging topic by equipping them with concrete tools, communication training, and clear treatment directives. From a societal perspective, primary care holds a unique position to identify hazardous and harmful alcohol use across different age groups, with potential public health and economic benefits through early identification and intervention.
TRIAL REGISTRATION
Clinicaltrials.gov NCT05916027. Retrospectively registered 22 June 2023.
Topics: Humans; Primary Health Care; Denmark; Naltrexone; Alcoholism; Male; Female; Alcohol Deterrents; Disulfiram; Acamprosate; Adult; Taurine; Alanine Transaminase; gamma-Glutamyltransferase; Middle Aged; Mass Screening; Randomized Controlled Trials as Topic
PubMed: 38872214
DOI: 10.1186/s13722-024-00474-6 -
Health Technology Assessment... Oct 2023Acamprosate is an effective and cost-effective medication for alcohol relapse prevention but poor adherence can limit its full benefit. Effective interventions to... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Acamprosate is an effective and cost-effective medication for alcohol relapse prevention but poor adherence can limit its full benefit. Effective interventions to support adherence to acamprosate are therefore needed.
OBJECTIVES
To determine the effectiveness of Medication Management, with and without Contingency Management, compared to Standard Support alone in enhancing adherence to acamprosate and the impact of adherence to acamprosate on abstinence and reduced alcohol consumption.
DESIGN
Multicentre, three-arm, parallel-group, randomised controlled clinical trial.
SETTING
Specialist alcohol treatment services in five regions of England (South East London, Central and North West London, Wessex, Yorkshire and Humber and West Midlands).
PARTICIPANTS
Adults (aged 18 years or more), an , Tenth Revision, diagnosis of alcohol dependence, abstinent from alcohol at baseline assessment, in receipt of a prescription for acamprosate.
INTERVENTIONS
(1) Standard Support, (2) Standard Support with adjunctive Medication Management provided by pharmacists via a clinical contact centre (12 sessions over 6 months), (3) Standard Support with adjunctive Medication Management plus Contingency Management that consisted of vouchers (up to £120) to reinforce participation in Medication Management. Consenting participants were randomised in a 2 : 1 : 1 ratio to one of the three groups using a stratified random permuted block method using a remote system. Participants and researchers were not blind to treatment allocation.
MAIN OUTCOME MEASURES
Primary outcome: self-reported percentage of medication taken in the previous 28 days at 6 months post randomisation. Economic outcome: EuroQol-5 Dimensions, a five-level version, used to calculate quality-adjusted life-years, with costs estimated using the Adult Service Use Schedule.
RESULTS
Of the 1459 potential participants approached, 1019 (70%) were assessed and 739 (73 consented to participate in the study, 372 (50%) were allocated to Standard Support, 182 (25%) to Standard Support with Medication Management and 185 (25%) to Standard Support and Medication Management with Contingency Management. Data were available for 518 (70%) of participants at 6-month follow-up, 255 (68.5%) allocated to Standard Support, 122 (67.0%) to Standard Support and Medication Management and 141 (76.2%) to Standard Support and Medication Management with Contingency Management. The mean difference of per cent adherence to acamprosate was higher for those who received Standard Support and Medication Management with Contingency Management (10.6%, 95% confidence interval 19.6% to 1.6%) compared to Standard Support alone, at the primary end point (6-month follow-up). There was no significant difference in per cent days adherent when comparing Standard Support and Medication Management with Standard Support alone 3.1% (95% confidence interval 12.8% to -6.5%) or comparing Standard Support and Medication Management with Standard Support and Medication Management with Contingency Management 7.9% (95% confidence interval 18.7% to -2.8%). The primary economic analysis at 6 months found that Standard Support and Medication Management with Contingency Management was cost-effective compared to Standard Support alone, achieving small gains in quality-adjusted life-years at a lower cost per participant. Cost-effectiveness was not observed for adjunctive Medication Management compared to Standard Support alone. There were no serious adverse events related to the trial interventions reported.
LIMITATIONS
The trial's primary outcome measure changed substantially due to data collection difficulties and therefore relied on a measure of self-reported adherence. A lower than anticipated follow-up rate at 12 months may have lowered the statistical power to detect differences in the secondary analyses, although the primary analysis was not impacted.
CONCLUSIONS
Medication Management enhanced with Contingency Management is beneficial to patients for supporting them to take acamprosate.
FUTURE WORK
Given our findings in relation to Contingency Management enhancing Medication Management adherence, future trials should be developed to explore its effectiveness and cost-effectiveness with other alcohol interventions where there is evidence of poor adherence.
TRIAL REGISTRATION
This trial is registered as ISRCTN17083622 https://doi.org/10.1186/ISRCTN17083622.
FUNDING
This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 27, No. 22. See the NIHR Journals Library website for further project information.
Topics: Adult; Humans; Acamprosate; Alcoholism; Medication Therapy Management; Behavior Therapy; England; Cost-Benefit Analysis; Quality of Life
PubMed: 37924307
DOI: 10.3310/DQKL6124 -
Neuropharmacology May 2024Repurposing regulatory agency-approved molecules, with proven safety in humans, is an attractive option for developing new treatments for disease. We identified and...
Repurposing regulatory agency-approved molecules, with proven safety in humans, is an attractive option for developing new treatments for disease. We identified and assessed the efficacy of 3 drugs predicted by an in silico screen as having the potential to treat l-DOPA-induced dyskinesia (LID) in Parkinson's disease. We analysed ∼1.3 million Medline abstracts using natural language processing and ranked 3539 existing drugs based on predicted ability to reduce LID. 3 drugs from the top 5% of the 3539 candidates; lorcaserin, acamprosate and ganaxolone, were prioritized for preclinical testing based on i) having a novel mechanism of action, ii) having not been previously validated for the treatment of LID, iii) being blood-brain-barrier penetrant and orally bioavailable and iv) being clinical trial ready. We assessed the efficacy of acamprosate, ganaxolone and lorcaserin in a rodent model of l-DOPA-induced hyperactivity, with lorcaserin affording a 58% reduction in rotational asymmetry (P < 0.05) compared to vehicle. Acamprosate and ganaxolone failed to demonstrate efficacy. Lorcaserin, a 5HT2C agonist, was then further tested in MPTP lesioned dyskinetic macaques where it afforded an 82% reduction in LID (P < 0.05), unfortunately accompanied by a significant increase in parkinsonian disability. In conclusion, although our data do not support the repurposing of lorcaserin, acamprosate or ganaxolone per se for LID, we demonstrate value of an in silico approach to identify candidate molecules which, in combination with an in vivo screen, can facilitate clinical development decisions. The present study adds to a growing literature in support of this paradigm shifting approach in the repurposing pipeline.
Topics: Humans; Animals; Levodopa; Artificial Intelligence; Drug Repositioning; Acamprosate; Dyskinesia, Drug-Induced; Macaca; Antiparkinson Agents; Disease Models, Animal
PubMed: 38412888
DOI: 10.1016/j.neuropharm.2024.109880