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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 -
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 -
The Cochrane Database of Systematic... May 2023Harmful alcohol use is defined as unhealthy alcohol use that results in adverse physical, psychological, social, or societal consequences and is among the leading risk... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Harmful alcohol use is defined as unhealthy alcohol use that results in adverse physical, psychological, social, or societal consequences and is among the leading risk factors for disease, disability and premature mortality globally. The burden of harmful alcohol use is increasing in low- and middle-income countries (LMICs) and there remains a large unmet need for indicated prevention and treatment interventions to reduce harmful alcohol use in these settings. Evidence regarding which interventions are effective and feasible for addressing harmful and other patterns of unhealthy alcohol use in LMICs is limited, which contributes to this gap in services.
OBJECTIVES
To assess the efficacy and safety of psychosocial and pharmacologic treatment and indicated prevention interventions compared with control conditions (wait list, placebo, no treatment, standard care, or active control condition) aimed at reducing harmful alcohol use in LMICs.
SEARCH METHODS
We searched for randomized controlled trials (RCTs) indexed in the Cochrane Drugs and Alcohol Group (CDAG) Specialized Register, the Cochrane Clinical Register of Controlled Trials (CENTRAL) in the Cochrane Library, PubMed, Embase, PsycINFO, CINAHL, and the Latin American and Caribbean Health Sciences Literature (LILACS) through 12 December 2021. We searched clinicaltrials.gov, the World Health Organization International Clinical Trials Registry Platform, Web of Science, and Opengrey database to identify unpublished or ongoing studies. We searched the reference lists of included studies and relevant review articles for eligible studies.
SELECTION CRITERIA
All RCTs comparing an indicated prevention or treatment intervention (pharmacologic or psychosocial) versus a control condition for people with harmful alcohol use in LMICs were included.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included 66 RCTs with 17,626 participants. Sixty-two of these trials contributed to the meta-analysis. Sixty-three studies were conducted in middle-income countries (MICs), and the remaining three studies were conducted in low-income countries (LICs). Twenty-five trials exclusively enrolled participants with alcohol use disorder. The remaining 51 trials enrolled participants with harmful alcohol use, some of which included both cases of alcohol use disorder and people reporting hazardous alcohol use patterns that did not meet criteria for disorder. Fifty-two RCTs assessed the efficacy of psychosocial interventions; 27 were brief interventions primarily based on motivational interviewing and were compared to brief advice, information, or assessment only. We are uncertain whether a reduction in harmful alcohol use is attributable to brief interventions given the high levels of heterogeneity among included studies (Studies reporting continuous outcomes: Tau² = 0.15, Q =139.64, df =16, P<.001, I² = 89%, 3913 participants, 17 trials, very low certainty; Studies reporting dichotomous outcomes: Tau²=0.18, Q=58.26, df=3, P<.001, I² =95%, 1349 participants, 4 trials, very low certainty). The other types of psychosocial interventions included a range of therapeutic approaches such as behavioral risk reduction, cognitive-behavioral therapy, contingency management, rational emotive therapy, and relapse prevention. These interventions were most commonly compared to usual care involving varying combinations of psychoeducation, counseling, and pharmacotherapy. We are uncertain whether a reduction in harmful alcohol use is attributable to psychosocial treatments due to high levels of heterogeneity among included studies (Heterogeneity: Tau² = 1.15; Q = 444.32, df = 11, P<.001; I²=98%, 2106 participants, 12 trials, very low certainty). Eight trials compared combined pharmacologic and psychosocial interventions with placebo, psychosocial intervention alone, or another pharmacologic treatment. The active pharmacologic study conditions included disulfiram, naltrexone, ondansetron, or topiramate. The psychosocial components of these interventions included counseling, encouragement to attend Alcoholics Anonymous, motivational interviewing, brief cognitive-behavioral therapy, or other psychotherapy (not specified). Analysis of studies comparing a combined pharmacologic and psychosocial intervention to psychosocial intervention alone found that the combined approach may be associated with a greater reduction in harmful alcohol use (standardized mean difference (standardized mean difference (SMD))=-0.43, 95% confidence interval (CI): -0.61 to -0.24; 475 participants; 4 trials; low certainty). Four trials compared pharmacologic intervention alone with placebo and three with another pharmacotherapy. Drugs assessed were: acamprosate, amitriptyline, baclofen disulfiram, gabapentin, mirtazapine, and naltrexone. None of these trials evaluated the primary clinical outcome of interest, harmful alcohol use. Thirty-one trials reported rates of retention in the intervention. Meta-analyses revealed that rates of retention between study conditions did not differ in any of the comparisons (pharmacologic risk ratio (RR) = 1.13, 95% CI: 0.89 to 1.44, 247 participants, 3 trials, low certainty; pharmacologic in addition to psychosocial intervention: RR = 1.15, 95% CI: 0.95 to 1.40, 363 participants, 3 trials, moderate certainty). Due to high levels of heterogeneity, we did not calculate pooled estimates comparing retention in brief (Heterogeneity: Tau² = 0.00; Q = 172.59, df = 11, P<.001; I = 94%; 5380 participants; 12 trials, very low certainty) or other psychosocial interventions (Heterogeneity: Tau² = 0.01; Q = 34.07, df = 8, P<.001; I = 77%; 1664 participants; 9 trials, very low certainty). Two pharmacologic trials and three combined pharmacologic and psychosocial trials reported on side effects. These studies found more side effects attributable to amitriptyline relative to mirtazapine, naltrexone and topiramate relative to placebo, yet no differences in side effects between placebo and either acamprosate or ondansetron. Across all intervention types there was substantial risk of bias. Primary threats to validity included lack of blinding and differential/high rates of attrition.
AUTHORS' CONCLUSIONS
In LMICs there is low-certainty evidence supporting the efficacy of combined psychosocial and pharmacologic interventions on reducing harmful alcohol use relative to psychosocial interventions alone. There is insufficient evidence to determine the efficacy of pharmacologic or psychosocial interventions on reducing harmful alcohol use largely due to the substantial heterogeneity in outcomes, comparisons, and interventions that precluded pooling of these data in meta-analyses. The majority of studies are brief interventions, primarily among men, and using measures that have not been validated in the target population. Confidence in these results is reduced by the risk of bias and significant heterogeneity among studies as well as the heterogeneity of results on different outcome measures within studies. More evidence on the efficacy of pharmacologic interventions, specific types of psychosocial interventions are needed to increase the certainty of these results.
Topics: Humans; Male; Acamprosate; Alcoholism; Amitriptyline; Developing Countries; Disulfiram; Mirtazapine; Naltrexone; Ondansetron; Topiramate
PubMed: 37158538
DOI: 10.1002/14651858.CD013350.pub2 -
The Cochrane Database of Systematic... Jan 2023Alcohol use disorder (AUD) is one of the most widespread psychiatric disorders leading to detrimental consequences to people with this disorder and others. Worldwide,... (Review)
Review
BACKGROUND
Alcohol use disorder (AUD) is one of the most widespread psychiatric disorders leading to detrimental consequences to people with this disorder and others. Worldwide, the prevalence of heavy episodic drinking (30-day prevalence of at least one occasion of 60 g of pure alcohol intake among current drinkers) is estimated at 20% and the prevalence of AUD at 5% of the adult general population, with highest prevalence in Europe and North America. Therapeutic approaches, including pharmacotherapy, play an important role in treating people with AUD. This is an update of a Cochrane Review first published in 2018.
OBJECTIVES
To evaluate the benefits and harms of baclofen on achieving and maintaining abstinence or reducing alcohol consumption in people with AUD compared to placebo, no treatment or any other pharmacological relapse prevention treatment.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search was 22 November 2021.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of at least four weeks' treatment duration and 12 weeks' overall study duration comparing baclofen for AUD treatment with placebo, no treatment or other treatments.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were 1. relapse, 2. frequency of use, 3. amount of use, 4. adverse events, 5. dropouts from treatment and 6. dropouts from treatment due to adverse events. Our secondary outcomes were 7. craving, 8. anxiety, 9. depression and 10. frequency of most relevant adverse events.
MAIN RESULTS
We included 17 RCTs (1818 participants) with a diagnosis of alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition or International Classification of Diseases 10th edition criteria. Mean age was 46.5 years and 70% were men. Ten studies compared baclofen to placebo or another medication; seven compared two baclofen doses to placebo or another medication. Globally, 15 studies compared baclofen to placebo, two baclofen to acamprosate and two baclofen to naltrexone. In 16 studies, participants received psychosocial treatments. We judged most studies at low risk of selection, performance, detection (subjective outcome), attrition and reporting bias. Ten studies detoxified participants before treatment; in seven studies, participants were still drinking at the beginning of treatment. Treatment duration was 12 weeks for 15 RCTs and longer in two studies. Baclofen daily dose was 30 mg to 300 mg: 10 RCTs used low doses (30 mg or less); eight RCTs medium doses (above 30 and 100 mg or less) and four RCTs high doses (above 100 mg). Compared to placebo, moderate-certainty evidence found that baclofen probably decreases the risk to relapse (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.77 to 0.99; 12 studies, 1057 participants). This result was confirmed among detoxified participants but not among other subgroups of participants. High-certainty evidence found that baclofen increases the percentage of days abstinent (mean difference (MD) 9.07, 95% CI 3.30 to 14.85; 16 studies, 1273 participants). This result was confirmed among all subgroups of participants except non-detoxified or those who received medium doses. There was no difference between baclofen and placebo in the other primary outcomes: heavy drinking days (standardised mean difference (SMD) -0.18, 95% CI -0.48 to 0.11; 13 studies, 840 participants; moderate-certainty evidence); number of drinks per drinking days (MD -0.45, 95% CI -1.20 to 0.30; 9 studies, 392 participants; moderate-certainty evidence); number of participants with at least one adverse event (RR 1.05, 95% CI 0.99 to 1.11; 10 studies, 738 participants; high-certainty evidence); dropouts (RR 0.88, 95% CI 0.74 to 1.03; 17 studies, 1563 participants; high-certainty evidence); dropouts due to adverse events (RR 1.39, 95% CI 0.89 to 2.18; 16 studies, 1499 participants; high-certainty evidence). These results were confirmed by subgroup analyses except than for the dropouts that resulted lower among participants who received high doses of baclofen and studies longer than 12 weeks. Compared to placebo, there was no difference in craving (SMD -0.16, 95% CI -0.37 to 0.04; 17 studies, 1275 participants), anxiety (MD -0.01, 95% CI -0.14 to 0.11; 15 studies, 1123 participants) and depression (SMD 0.07, 95% CI -0.12 to 0.27; 11 studies, 1029 participants). Concerning the specific adverse events, baclofen increases fatigue, dizziness, somnolence/sedation, dry mouth, paraesthesia and muscle spasms/rigidity. There was no difference in the other adverse events. Compared to acamprosate, one study (60 participants) found no differences in any outcomes but the evidence was very uncertain: relapse (RR 1.25, 95% CI 0.71 to 2.20; very low-certainty evidence); number of participants with at least one adverse event (RR 0.63, 95% CI 0.23 to 1.69; very low-certainty evidence); dropouts (RR 0.56, 95% CI 0.21 to 1.46; very low-certainty evidence); dropouts due to adverse events (RR 0.33, 95% CI 0.01 to 7.87; very low-certainty evidence) and craving (MD 5.80, 95% CI -11.84 to 23.44); and all the adverse events evaluated. Compared to naltrexone, baclofen may increase the risk of relapse (RR 2.50, 95% CI 1.12 to 5.56; 1 study, 60 participants; very low-certainty evidence) and decrease the number of participants with at least one adverse event (RR 0.35, 95% CI 0.15 to 0.80; 2 studies, 80 participants; very low-certainty evidence) but the evidence is very uncertain. One study (60 participants) found no difference between baclofen and naltrexone in the dropouts at the end of treatment (RR 1.00, 95% CI 0.32 to 3.10; very low-certainty evidence), craving (MD 2.08, 95% CI -3.71 to 7.87), and all the adverse events evaluated.
AUTHORS' CONCLUSIONS
Baclofen likely reduces the risk of relapse to any drinking and increases the percentage of abstinent days, mainly among detoxified participants. It does not increase the number of participants with at least one adverse event, those who dropout for any reason or due to adverse events. It probably does not reduce number of heavy drinking days and the number of drinks per drinking days. Current evidence suggests that baclofen may help people with AUD in maintaining abstinence. The results of comparisons of baclofen with acamprosate and naltrexone were mainly based on only one study.
Topics: Adult; Female; Humans; Male; Middle Aged; Acamprosate; Alcohol Drinking; Alcoholism; Baclofen; Chronic Disease; Naltrexone
PubMed: 36637087
DOI: 10.1002/14651858.CD012557.pub3 -
Journal of Studies on Alcohol and Drugs Jul 2022This article reviews research on post-acute alcohol withdrawal syndrome (PAWS) management.
OBJECTIVE
This article reviews research on post-acute alcohol withdrawal syndrome (PAWS) management.
METHOD
We conducted a PRISMA (Preferred Reporting Items for Systematic Revision and Meta-Analyses)-guided scoping review of the published PAWS literature, searching six electronic databases (from their inception through December 2020) for English-language randomized and nonrandomized studies.
RESULTS
A total of 16 treatment studies met the inclusion criteria. The strength of evidence overall for pharmacologic treatments is low, with often only short-term results being reported, small treatment samples used, or inconsistent results found. However, for negative affect and sleep symptoms, more evidence supports using gabapentinoids (gabapentin and pregabalin) and anticonvulsants (carbamazepine and oxcarbazepine). Although preliminary data support acamprosate, there were no controlled trials. Despite an older treatment trial showing some positive data for amitriptyline for mood, the clinical measures used were problematic, and side effects and safety profile limit its utility. Finally, there is no evidence that melatonin and other agents (homatropine, Proproten-100) show PAWS symptoms.
CONCLUSIONS
Although there is some evidence for targeted pharmacotherapy for treating specific PAWS symptoms, there are few recent, robust, placebo-controlled trials, and the level of evidence for treatment efficacy is low.
Topics: Alcoholism; Anticonvulsants; Benzodiazepines; Gabapentin; Humans; Substance Withdrawal Syndrome
PubMed: 35838423
DOI: 10.15288/jsad.2022.83.470 -
Journal of Addiction MedicineWe aimed to determine medications' comparative efficacy and safety for adults with alcohol use disorders. (Meta-Analysis)
Meta-Analysis
BACKGROUND
We aimed to determine medications' comparative efficacy and safety for adults with alcohol use disorders.
METHODS
We searched eleven electronic data sources for randomized clinical trials with at least 4 weeks of treatment reporting on alcohol consumption (total abstinence and reduced heavy drinking), dropouts, and dropouts due to adverse events. We conducted network meta-analyses using random-effects, frequentist models, and calculated summary rate ratios (RRs) with 95% confidence intervals (CIs).
RESULTS
We included 156 trials (N = 27,334). Nefazodone (RR = 2.11; 95% CI, 1.42-3.13), aripiprazole (RR = 1.97; 95% CI, 1.36-2.88), carbamazepine (RR = 1.85; 95% CI, 1.03-3.32), and nalmefene (RR = 1.17; 95% CI, 1.01-1.35) were associated with the most dropouts. Baclofen (RR = 0.83; 95% CI, 0.70-0.97) and pregabalin (RR = 0.63; 95% CI, 0.43-0.94) caused fewer dropouts than placebo. Nalmefene (RR = 3.26; 95% CI, 2.34-4.55), fluvoxamine (RR = 3.08; 95% CI, 1.59-5.94), and topiramate (RR=2.18; 95% CI, 1.36-3.51) caused more dropouts from adverse events over placebo. Gamma-hydroxy-butyrate (RR = 1.90; 95% CI, 1.03-3.53), baclofen (RR = 1.80; 95% CI, 1.39-2.34), disulfiram (RR = 1.71; 95% CI, 1.39-2.10), gabapentin (RR = 1.66; 95% CI, 1.04-2.67), acamprosate (RR = 1.33; 95% CI, 1.15-1.54), and oral naltrexone (RR = 1.15; 95% CI, 1.01-1.32) improved total abstinence over placebo (Fig. 3C). For reduced heavy drinking, disulfiram (RR = 0.19; 95% CI, 0.10-0.35), baclofen (RR = 0.72; 95% CI, 0.57-0.91), acamprosate (RR = 0.78; 95% CI, 0.70-0.86), and oral naltrexone (RR = 0.81; 95% CI, 0.73-0.90) were efficacious against placebo.
CONCLUSIONS
The current meta-analyses provide evidence that several medications for AUDs are effective and safe and encourage the expanded use of these medications in the clinical setting. Our review found that acamprosate (2-3 g/d), disulfiram (250-500 mg/d), baclofen (30 mg/d), and oral naltrexone (50 mg/d) had the best evidence for improving abstinence and heavy drinking for patients with AUD.
PROSPERO
CRD42020208946.
Topics: Adult; Humans; Acamprosate; Alcoholism; Baclofen; Disulfiram; Naltrexone; Network Meta-Analysis; Randomized Controlled Trials as Topic
PubMed: 35653782
DOI: 10.1097/ADM.0000000000000992 -
Brain Sciences Mar 2022Although Alcohol Use Disorder (AUD) is highly prevalent worldwide, treating this condition remains challenging. Further, potential treatments for AUD do not fully... (Review)
Review
BACKGROUND
Although Alcohol Use Disorder (AUD) is highly prevalent worldwide, treating this condition remains challenging. Further, potential treatments for AUD do not fully address alcohol-induced neuroadaptive changes. Understanding the effects of pharmacotherapies for AUD on the human brain may lead to tailored, more effective treatments, and improved individual clinical outcomes.
OBJECTIVES
We systematically reviewed the literature for studies investigating pharmacotherapies for AUD that included neuroimaging-based treatment outcomes. We searched the PubMed, Scielo, and PsycINFO databases up to January 2021.
STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS
Eligible studies included those investigating pharmacotherapies for AUD and employing functional magnetic resonance imaging (fMRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT), and/or proton magnetic resonance spectroscopy (H-MRS).
STUDY APPRAISAL AND SYNTHESIS METHODS
Two independent reviewers screened studies' titles and abstracts for inclusion. Data extraction forms were shared among all the authors to standardize data collection. We gathered information on the following variables: sample size; mean age; sociodemographic and clinical characteristics; alcohol use status; study design and methodology; main neuroimaging findings and brain-regions of interest (i.e., brain areas activated by alcohol use and possible pharmacological interactions); and limitations of each study.
RESULTS
Out of 177 studies selected, 20 studies provided relevant data for the research topic. Findings indicate that: (1) Acamprosate and gabapentin may selectively modulate limbic regions and the anterior cingulate cortex; (2) Naltrexone and disulfiram effects may involve prefrontal, premotor, and cerebellar regions; (3) Pharmacotherapies acting on glutamate and GABA neurotransmission involve primarily areas underpinning reward and negative affective states, and; (4) Pharmacotherapies acting on opioid and dopamine systems may affect areas responsible for the cognitive and motor factors of AUD.
LIMITATIONS
Most of the studies were focused on naltrexone. A small number of studies investigated the action of disulfiram and gabapentin, and no neuroimaging studies investigated topiramate. In addition, the time between medication and neuroimaging scans varied widely across studies.
CONCLUSIONS
We identified key-brain regions modulated by treatments available for AUD. Some of the regions modulated by naltrexone are not specific to the brain reward system, such as the parahippocampal gyrus (temporal lobe), parietal and occipital lobes. Other treatments also modulate not specific regions of the reward system, but play a role in the addictive behaviors, including the insula and dorsolateral prefrontal cortex. The role of these brain regions in mediating the AUD pharmacotherapy response warrants investigation in future research studies.
PubMed: 35326342
DOI: 10.3390/brainsci12030386 -
PloS One 2022The current research aims to systematically review the rates of adherence reported in randomised controlled clinical trials of acamprosate. It also sought to determine...
AIM
The current research aims to systematically review the rates of adherence reported in randomised controlled clinical trials of acamprosate. It also sought to determine the reliability of the adherence monitoring and measurement methods used in these trials.
METHODS
The protocol for this review was pre-registered (PROSPERO: CRD42021230011). A search of the literature was conducted using OVID MEDLINE, Embase and PsycINFO from database inception to January 2021. Randomised controlled trials with a minimum sample size of 10 per treatment arm that compared the efficacy of acamprosate with placebo or other active medication in adults with a diagnosis of alcohol dependence were included. Data on rates of adherence, methods of measurement and monitoring of adherence was extracted from eligible studies independently in duplicate by two reviewers. A weighted mean adherence rate was calculated. The reliability of adherence monitoring methods was determined by calculating an adherence-assurance score based on the adherence monitoring method used. Risk of bias was assessed using the Cochrane Risk of Bias Tool.
RESULTS
Fifteen studies met the eligibility criteria involving 4,450 participants (2,480 participants in the placebo arms). A mean adherence rate of 88% (54.2-95.0%) was reported across studies that reported the percentage of medication taken. A mean adherence rate of 84.9% (56.4-91.3%) was reported for trials that reported the percentage of participants taking more than 80% of medication prescribed. There is low confidence in the methods used to monitor adherence with all clinical trials having a low adherence-assurance rating. Risk of bias was judged to be high for all included studies.
CONCLUSIONS
Adherence to acamprosate in clinical trials can be poor with low confidence in the methods used to measure it. Adherence rates therefore might not be accurate, which has implications for determining the efficacy of acamprosate.
Topics: Acamprosate; Adult; Alcohol Deterrents; Alcoholism; Clinical Decision-Making; Humans; Medication Adherence; Middle Aged; Randomized Controlled Trials as Topic; Reproducibility of Results
PubMed: 35113930
DOI: 10.1371/journal.pone.0263350 -
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