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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 -
Addiction (Abingdon, England) Oct 2022There have been few head-to-head clinical trials of pharmacotherapies for alcohol withdrawal (AW). We, therefore, aimed to evaluate the comparative performance of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
There have been few head-to-head clinical trials of pharmacotherapies for alcohol withdrawal (AW). We, therefore, aimed to evaluate the comparative performance of pharmacotherapies for AW.
METHODS
Six databases were searched for randomized clinical trials through November 2021. Trials were included after a blinded review by two independent reviewers. Outcomes included incident seizures, delirium tremens, AW severity scores, adverse events, dropouts, dropouts from adverse events, length of hospital stay, use of additional medications, total benzodiazepine requirements, and death. Effect sizes were pooled using frequentist random-effects network meta-analysis models to generate summary ORs and Cohen's d standardized mean differences (SMDs).
RESULTS
Across the 149 trials, there were 10 692 participants (76% male, median 43.5 years old). AW severity spanned mild (n = 32), moderate (n = 51), and severe (n = 66). Fixed-schedule chlormethiazole (OR, 0.16; 95% CI, 0.04-0.65), fixed-schedule diazepam (OR, 0.16; 95% CI, 0.04-0.59), fixed-schedule lorazepam (OR = 0.19; 95% CI, 0.08-0.45), fixed-schedule chlordiazepoxide (OR = 0.21; 95% CI, 0.08-0.53), and divalproex (OR = 0.22; 95% CI, 0.05-0.86) were superior to placebo at reducing incident AW seizures. However, only fixed-schedule diazepam (OR, 0.19; 95% CI, 0.05-0.76) reduced incident delirium tremens. Oxcarbazepine (d = -3.69; 95% CI, -6.21 to -1.17), carbamazepine (d = -2.76; 95% CI, -4.13 to -1.40), fixed-schedule oxazepam (d = -2.55; 95% CI, -4.26 to -0.83), and γ-hydroxybutyrate (d = -1.80; 95% CI, -3.35 to -0.26) improved endpoint Clinical Institute Withdrawal Assessment for Alcohol-Revised scores over placebo. Promazine and carbamazepine were the only agents significantly associated with greater dropouts because of adverse events. The quality of evidence was downgraded because of the substantial risk of bias, heterogeneity, inconsistency, and imprecision.
CONCLUSIONS
Although some pharmacotherapeutic modalities, particularly benzodiazepines, appear to be safe and efficacious for reducing some measures of alcohol withdrawal, methodological issues and a high risk of bias prevent a consistent estimate of their comparative performance.
Topics: Adult; Alcohol Withdrawal Delirium; Alcoholism; Benzodiazepines; Carbamazepine; Diazepam; Female; Humans; Male; Network Meta-Analysis; Seizures; Substance Withdrawal Syndrome
PubMed: 35194860
DOI: 10.1111/add.15853 -
Magnesium Research Nov 2017Increasing evidence supports a role of magnesium (Mg) in skeletal muscle function. However, no systematic review or meta-analysis has summarized data on Mg... (Meta-Analysis)
Meta-Analysis Review
Increasing evidence supports a role of magnesium (Mg) in skeletal muscle function. However, no systematic review or meta-analysis has summarized data on Mg supplementation in relation to muscle fitness in humans. Thus, this study aimed to quantitatively assess the effect of Mg supplementation on muscle fitness. A meta-analysis and systematic review. Medline database and other sources were searched for randomized clinical trials through July 2017. Studies that reported results regarding at least one of the following outcomes: leg strength, knee extension strength, peak torque, muscle power, muscle work, jump, handgrip, bench press weights, resistant exercise, lean mass, muscle mass, muscle strength, walking speed, Repeated Chair Stands, and TGUG were included. Measurements of the association were pooled using a fixed-effects model and expressed as weighted mean differences (WMDs) with 95% confidence intervals (95% CIs). Fourteen randomized clinical trials targeting 3 different populations were identified: athletes or physically active individuals (215 participants; mean age: 24.9 years), untrained healthy individuals (95 participants; mean age: 40.2 years), and elderly or alcoholics (232 participants; mean age: 62.7 years). The beneficial effects of Mg supplementation appeared to be more pronounced in the elderly and alcoholics, but were not apparent in athletes and physically active individuals. The results of the meta-analysis suggested that no significant improvements in the supplementation group were observed regarding isokinetic peak torque extension [WMD = 0.87; 95% CI = (-1.43, 3.18)], muscle strength [WMD = 0.87; 95% CI = (-0.12, 1.86)] or muscle power [WMD = 3.28; 95% CI = (-14.94, 21.50)]. Evidence does not support a beneficial effect of Mg supplementation on muscle fitness in most athletes and physically active individuals who have a relatively high Mg status. But Mg supplementation may benefit individuals with Mg deficiency, such as the elderly and alcoholics.
Topics: Adult; Aged; Alcoholism; Athletes; Dietary Supplements; Exercise; Female; Humans; Magnesium; Male; Muscle Strength
PubMed: 29637897
DOI: 10.1684/mrh.2018.0430 -
BMJ (Clinical Research Ed.) Nov 2020To determine the most effective interventions in recently detoxified, alcohol dependent patients for implementation in primary care. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine the most effective interventions in recently detoxified, alcohol dependent patients for implementation in primary care.
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
Medline, Embase, PsycINFO, Cochrane CENTRAL, ClinicalTrials.gov, and the World Health Organization's International Clinical Trials Registry Platform.
STUDY SELECTION
Randomised controlled trials comparing two or more interventions that could be used in primary care. The population was patients with alcohol dependency diagnosed by standardised clinical tools and who became detoxified within four weeks.
DATA EXTRACTION
Outcomes of interest were continuous abstinence from alcohol (effectiveness) and all cause dropouts (as a proxy for acceptability) at least 12 weeks after start of intervention.
RESULTS
64 trials (43 interventions) were included. The median probability of abstinence across placebo arms was 25%. Compared with placebo, the only intervention associated with increased probability of abstinence and moderate certainty evidence was acamprosate (odds ratio 1.86, 95% confidence interval 1.49 to 2.33, corresponding to an absolute probability of 38%). Of the 62 included trials that reported all cause dropouts, interventions associated with a reduced number of dropouts compared with placebo (probability 50%) and moderate certainty of evidence were acamprosate (0.73, 0.62 to 0.86; 42%), naltrexone (0.70, 0.50 to 0.98; 41%), and acamprosate-naltrexone (0.30, 0.13 to 0.67; 17%). Acamprosate was the only intervention associated with moderate confidence in the evidence of effectiveness and acceptability up to 12 months. It is uncertain whether other interventions can help maintain abstinence and reduce dropouts because of low confidence in the evidence.
CONCLUSIONS
Evidence is lacking for benefit from interventions that could be implemented in primary care settings for alcohol abstinence, other than for acamprosate. More evidence from high quality randomised controlled trials is needed, as are strategies using combined interventions (combinations of drug interventions or drug and psychosocial interventions) to improve treatment of alcohol dependency in primary care.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42016049779.
Topics: Adult; Alcohol Abstinence; Alcoholism; Behavior Therapy; Female; Humans; Male; Middle Aged; Network Meta-Analysis; Primary Health Care; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 33239318
DOI: 10.1136/bmj.m3934 -
PloS One 2017Children of parents with drug and alcohol use disorders often grow up under severe stress and are at greater risk of developing psychological and social problems.... (Review)
Review
Children of parents with drug and alcohol use disorders often grow up under severe stress and are at greater risk of developing psychological and social problems. However, a substantial proportion of affected children adapt to their distressing life conditions and show positive development in terms of their mental health. These children are described as resilient. One difference between resilient and maladapted children is the presence of protective factors. The aim of this systematic review is to provide an overview of the current state of the research concerning protective mental health factors in children of parents with alcohol or drug use disorders (COPAD). For that purpose, the PsychInfo, PubMed, CINAHL and ISI Web of Science databases were searched through January 2017. All the identified publications were screened using previously developed inclusion criteria. The search yielded 3,402 articles. Eleven of these publications (2003-2013) met the criteria for inclusion in the present review. Information on the studies was extracted using an extraction form. A narrative analysis was performed, and the methodological quality was examined using a checklist based on the Mixed Methods Appraisal Tool. The research identified familial, parental, child-related and biological factors that influenced mental health outcomes in affected children (N = 1,376, age range = 1-20 years). Overall, protective mental health factors are understudied in this target group. Most of the included studies were conducted in the United States and employed a cross-sectional design. A comparison of the included cross-sectional and longitudinal studies indicated consistent results related to a secure parent-child attachment. Based on the current state of the research, no causal conclusions with regard to the effectiveness of protective factors can be drawn. To develop effective prevention programs, further longitudinal studies and studies assessing the interactions between risk and protective factors are needed.
Topics: Adolescent; Alcoholism; Child; Humans; Mental Health; Parent-Child Relations; Parenting; Parents; Protective Factors; Substance-Related Disorders
PubMed: 28609440
DOI: 10.1371/journal.pone.0179140 -
Cirugia Espanola Nov 2021Bariatric surgery is a relatively safe surgical procedure with a high success rate. However, recent reports indicate a higher prevalence of alcohol or substance abuse... (Review)
Review
INTRODUCTION
Bariatric surgery is a relatively safe surgical procedure with a high success rate. However, recent reports indicate a higher prevalence of alcohol or substance abuse disorder in this patient group. The purpose of this study was to review the related evidence to serve as a reference for multidisciplinary teams who treat these patients.
METHODS
We searched the PubMed and CENTRAL databases. The odds ratios were extracted from the different articles, comparing the prevalence of the abuse of alcohol or other substances in the postoperative period versus preoperative levels. We also compared the prevalence of alcohol use disorder after different types of bariatric surgery.
RESULTS
A total of 49 121 bariatric patients (80.8% female) were evaluated for alcohol use disorder. In general, bariatric surgery was found to be associated with an increase in the prevalence of alcohol abuse (4.58 ± 5.3 vs. 1.58 ± 10.7% in the preoperative period). We also found that the population of patients who underwent RYGB procedures had a higher prevalence of alcohol use disorder than patients who underwent another type of surgery (OR: 1.83; 95% CI: 1.51-2.21). The prevalence of substance abuse disorder (other than alcohol) after this procedure is less studied, although there appears to be an increased risk of abuse of certain substances.
CONCLUSIONS
Bariatric surgery is the best treatment for obesity and its complications. The evidence reviewed suggests that it correlates with a modest but consistent increase in the prevalence of abuse of alcohol and other substances. Medical teams who treat bariatric patients must be informed about this eventuality for its timely prevention, diagnosis and treatment.
Topics: Alcoholism; Bariatric Surgery; Ethanol; Female; Humans; Male; Obesity; Substance-Related Disorders
PubMed: 34690075
DOI: 10.1016/j.cireng.2021.10.004 -
The American Journal of Emergency... Jul 2023Alcohol Withdrawal Syndrome (AWS) among patients with chronic and heavy alcohol consumption can range from mild to severe and is associated with high morbidity and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Alcohol Withdrawal Syndrome (AWS) among patients with chronic and heavy alcohol consumption can range from mild to severe and is associated with high morbidity and mortality. Currently, treating AWS with benzodiazepines is the standard of care, but phenobarbital has also been hypothesized to be an effective first-line treatment due to its pharmacological properties and mechanism of action. We conducted a meta-analysis to review relevant literature and compare the clinical outcomes for patients diagnosed with AWS in ED and ICU settings.
METHODS
We performed a literature search in in the PubMed, Scopus, and Web of Science databases from inception to June 30, 2022. Randomized trials and observational (prospective or retrospective) studies were eligible if they included adult patients who presented in the ED and were treated in the ED and/or the intensive care unit (ICU) with a diagnosis of AWS. The primary outcome was the rate of intubation among patients who received phenobarbital, compared with benzodiazepines. Secondary outcomes such as rates of seizures, hospital, and ICU length of stay (LOS), also were included. The PROSPERO registration is CRD42022318862.
RESULTS
We included twelve studies (1934 patients) in our analysis. Of the 1934 patients in these studies, 765 (41.7%) were treated with phenobarbital and 1169 (58.3%) were treated with other modalities for alcohol withdrawal. Treating AWS patients with phenobarbital did not affect their risk for intubation, as the risk for intubation was similar between the phenobarbital and the control group (RR 0.70, 95% CI 0.36-1.38, P = 0.31). In addition, patients who were treated with phenobarbital were found to have similar rates of seizures (RR 0.73, 95% CI 0.29-1.89) and length of stay in the hospital (Standardized Mean Difference -0.02, 95% CI -0.26, 0.21) or the ICU (SMD -0.02, 95% CI -0.21, 0.25) when compared with patients receiving benzodiazepines.
CONCLUSIONS
Management of patients with AWS with phenobarbital is associated with similar rates of intubation, length of stay in the ICU, or length of stay in the hospital as treatment with benzodiazepines. However, due to the inclusion of mostly observational studies and a significant level of heterogeneity among the studies assessed in this review, additional trials with strong methodology are needed.
Topics: Adult; Humans; Substance Withdrawal Syndrome; Alcoholism; Retrospective Studies; Prospective Studies; Phenobarbital; Benzodiazepines; Seizures
PubMed: 37060631
DOI: 10.1016/j.ajem.2023.04.002 -
Addiction (Abingdon, England) Feb 2018Pharmacologically controlled drinking in the treatment of alcohol dependence or alcohol use disorders (AUDs) is an emerging concept. Our objective was to explore the... (Meta-Analysis)
Meta-Analysis
Pharmacologically controlled drinking in the treatment of alcohol dependence or alcohol use disorders: a systematic review with direct and network meta-analyses on nalmefene, naltrexone, acamprosate, baclofen and topiramate.
BACKGROUND AND AIMS
Pharmacologically controlled drinking in the treatment of alcohol dependence or alcohol use disorders (AUDs) is an emerging concept. Our objective was to explore the comparative effectiveness of drugs used in this indication.
DESIGN
Systematic review with direct and network meta-analysis of double-blind randomized controlled trials (RCTs) assessing the efficacy of nalmefene, naltrexone, acamprosate, baclofen or topiramate in non-abstinent adults diagnosed with alcohol dependence or AUDs. Two independent reviewers selected published and unpublished studies on Medline, the Cochrane Library, Embase, ClinicalTrials.gov, contacted pharmaceutical companies, the European Medicines Agency and the Food and Drug Administration, and extracted data.
SETTING
Thirty-two RCTs.
PARTICIPANTS
A total of 6036 patients.
MEASUREMENTS
The primary outcome was total alcohol consumption (TAC). Other consumption outcomes and health outcomes were considered as secondary outcomes.
FINDINGS
No study provided direct comparisons between drugs. A risk of incomplete outcome data was identified in 26 studies (81%) and risk of selective outcome reporting in 17 (53%). Nalmefene [standardized mean difference (SMD) = -0.19, 95% confidence interval (CI) = -0.29, -0.10; I = 0%], baclofen (SMD = -1.00, 95% CI = -1.80, -0.19; one study) and topiramate (SMD = -0.77, 95% CI = -1.12, -0.42; I = 0%) showed superiority over placebo on TAC. No efficacy was observed for naltrexone or acamprosate. Similar results were observed for other consumption outcomes, except for baclofen (the favourable outcome on TAC was not reproduced). The number of withdrawals for safety reasons increased under nalmefene and naltrexone. No treatment demonstrated any harm reduction (no study was powered to explore health outcomes). Indirect comparisons suggested that topiramate was superior to nalmefene, naltrexone and acamprosate on consumption outcomes, but its safety profile is known to be poor.
CONCLUSIONS
There is currently no high-grade evidence for pharmacological treatment to control drinking using nalmefene, naltrexone, acamprosate, baclofen or topiramate in patients with alcohol dependence or alcohol use disorder. Some treatments show low to medium efficacy in reducing drinking across a range of studies with a high risk of bias. None demonstrates any benefit on health outcomes.
Topics: Acamprosate; Alcoholism; Baclofen; Naltrexone; Narcotic Antagonists; Network Meta-Analysis; Topiramate; Treatment Outcome
PubMed: 28940866
DOI: 10.1111/add.13974 -
Addiction (Abingdon, England) Jun 2017Alcohol use is a major contributor to injuries, mortality and the burden of disease. This review updates knowledge on risk relations between dimensions of alcohol use... (Review)
Review
BACKGROUND AND AIMS
Alcohol use is a major contributor to injuries, mortality and the burden of disease. This review updates knowledge on risk relations between dimensions of alcohol use and health outcomes to be used in global and national Comparative Risk Assessments (CRAs).
METHODS
Systematic review of reviews and meta-analyses on alcohol consumption and health outcomes attributable to alcohol use. For dimensions of exposure: volume of alcohol use, blood alcohol concentration and patterns of drinking, in particular heavy drinking occasions were studied. For liver cirrhosis, quality of alcohol was additionally considered. For all outcomes (mortality and/or morbidity): cause of death and disease/injury categories based on International Classification of Diseases (ICD) codes used in global CRAs; harm to others.
RESULTS
In total, 255 reviews and meta-analyses were identified. Alcohol use was found to be linked causally to many disease and injury categories, with more than 40 ICD-10 three-digit categories being fully attributable to alcohol. Most partially attributable disease categories showed monotonic relationships with volume of alcohol use: the more alcohol consumed, the higher the risk of disease or death. Exceptions were ischaemic diseases and diabetes, with curvilinear relationships, and with beneficial effects of light to moderate drinking in people without heavy irregular drinking occasions. Biological pathways suggest an impact of heavy drinking occasions on additional diseases; however, the lack of medical epidemiological studies measuring this dimension of alcohol use precluded an in-depth analysis. For injuries, except suicide, blood alcohol concentration was the most important dimension of alcohol use. Alcohol use caused marked harm to others, which has not yet been researched sufficiently.
CONCLUSIONS
Research since 2010 confirms the importance of alcohol use as a risk factor for disease and injuries; for some health outcomes, more than one dimension of use needs to be considered. Epidemiological studies should include measurement of heavy drinking occasions in line with biological knowledge.
Topics: Alcoholism; Causality; Chronic Disease; Comorbidity; Cost of Illness; Health Status; Humans; Risk Assessment; Wounds and Injuries
PubMed: 28220587
DOI: 10.1111/add.13757 -
Drug and Alcohol Dependence Mar 2021Although the Clinical Institute Withdrawal Assessment for Alcohol - Revised (CIWA-Ar) is a gold standard tool for the clinical evaluation of alcohol withdrawal syndrome... (Meta-Analysis)
Meta-Analysis
Evaluation of the course and treatment of Alcohol Withdrawal Syndrome with the Clinical Institute Withdrawal Assessment for Alcohol - Revised: A systematic review-based meta-analysis.
BACKGROUND
Although the Clinical Institute Withdrawal Assessment for Alcohol - Revised (CIWA-Ar) is a gold standard tool for the clinical evaluation of alcohol withdrawal syndrome (AWS), a systematic analysis using the total scores of the CIWA-Ar as a means of an objective follow-up of the course and treatment of AWS is missing. The aims of the present study were to systematically evaluate scientific data using the CIWA-Ar, to reveal whether the aggregated CIWA-Ar total scores follow the course of AWS and to compare benzodiazepine (BZD) and non-benzodiazepine (nBZD) therapies in AWS.
METHODS
1054 findings were identified with the keyword "ciwa" from four databases (PubMed, ScienceDirect, Web of Science, Cochrane Registry). Articles using CIWA-Ar in patients treated with AWS were incorporated and two measurement intervals (cumulative mean data of day 1-3 and day 4-9) of the CIWA-Ar total scores were compared. Subgroup analysis based on pharmacotherapy regimen was conducted to compare the effectiveness of BZD and nBZD treatments.
RESULTS
The random effects analysis of 423 patients showed decreased CIWA-Ar scores between the two measurement intervals (BZD: d = -1.361; CI: -1.829 < δ < -0.893; nBZD: d = -0.858; CI: -1.073 < δ < -0.643). Sampling variances were calculated for the BZD (v = 0.215) and the nBZD (v = 0.106) groups, which indicated no significant group difference (z = -1.532).
CONCLUSIONS
Our findings support that the CIWA-Ar follows the course of AWS. Furthermore, nBZD therapy has a similar effectiveness compared to BZD treatment based on the CIWA-Ar total scores.
Topics: Adult; Alcoholism; Benzodiazepines; Ethanol; Female; Humans; Male; Middle Aged; Severity of Illness Index; Substance Withdrawal Syndrome
PubMed: 33503582
DOI: 10.1016/j.drugalcdep.2021.108536