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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Health Organization International Clinical Trials Registry Platform, Web of Science, and Opengrey database to identify unpublished or ongoing studies.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 Mental Health Clinician May 2021AUD medication treatment has been shown to improve outcomes compared with placebo when confined to per-protocol analysis. The same outcomes, however, have not always...
INTRODUCTION
AUD medication treatment has been shown to improve outcomes compared with placebo when confined to per-protocol analysis. The same outcomes, however, have not always been maintained in intent-to-treat analysis, thus suggesting adherence may have a significant impact on efficacy outcomes. There is conflicting evidence present in the literature comparing adherence to oral versus injectable AUD pharmacotherapy and a paucity of information in the veteran population on risk factors for low adherence.
METHODS
The primary end point of this retrospective chart review was to determine whether adherence rates differ between oral and injectable AUD treatments in veterans during the first year of treatment (at 3, 6, 9, and 12 months) using the portion of days covered model. Secondary end points were to determine differing characteristics between patients with high versus low adherence and compare alcohol-related readmission rates and discontinuation rates between groups.
RESULTS
Adherence to injectable extended-release (XR) naltrexone was significantly higher than oral naltrexone at all time points and was significantly higher than disulfiram at 3, 6, and 9 months, but it was not significantly different from acamprosate at any time point. At months 9 and 12, acamprosate had significantly higher adherence compared with oral naltrexone. Patients with higher adherence were seen more frequently in the mental health clinic and had previously tried more AUD medications. The discontinuation rates and alcohol-related admission rates were not significantly different between groups at 1 year.
DISCUSSION
XR naltrexone may improve adherence rates compared with oral naltrexone or disulfiram, but not acamprosate based on these outcomes. Patients may have increased adherence if they are seen more often in clinic and have trialed more AUD medications.
PubMed: 34026395
DOI: 10.9740/mhc.2021.05.194 -
Neuropharmacology Jul 2022Alcohol use disorder is associated with functional changes in the medial prefrontal cortex (mPFC), which include altered glutamatergic transmission and deficits in...
Alcohol use disorder is associated with functional changes in the medial prefrontal cortex (mPFC), which include altered glutamatergic transmission and deficits in executive functions that contribute to relapse. Acamprosate (calcium-bis N-acetylhomotaurinate) reduces alcohol craving and relapse, effects that are thought to be mediated by acamprosate's ability to ameliorate alcohol-induced dysregulation of glutamatergic signaling. Treatment with acamprosate and its active moiety calcium (CaCl) both improve deficits in cognitive flexibility in postdependent mice following chronic intermittent ethanol (CIE) exposure. Here, we show that mice that self-administered alcohol under goal-directed conditions (i.e., operant responding on a fixed-ratio schedule) also display similar deficits in cognitive flexibility and altered glutamatergic signaling in the mPFC, both of which were improved with acamprosate or CaCl. However, under conditions shown to bias behavior towards habitual responding (operant self-administration after CIE exposure, or on a variable interval schedule), alcohol-induced changes to glutamatergic transmission were unaffected by either acamprosate or CaCl treatment. Together, these findings suggest that the variable effects of acamprosate on synaptic signaling may reflect a shift in mPFC networks related to the loss of behavioral control in habitual alcohol-seeking.
Topics: Acamprosate; Animals; Calcium; Calcium Chloride; Ethanol; Mice; Prefrontal Cortex; Recurrence; Taurine
PubMed: 35430241
DOI: 10.1016/j.neuropharm.2022.109062 -
Addiction (Abingdon, England) Aug 2021Pharmacotherapy for alcohol use disorder (AUD) is recommendable, but under-used, possibly due to deficient knowledge of medications. This study aimed to investigate the...
BACKGROUND AND AIM
Pharmacotherapy for alcohol use disorder (AUD) is recommendable, but under-used, possibly due to deficient knowledge of medications. This study aimed to investigate the real-world effectiveness of approved pharmacological treatments (disulfiram, acamprosate, naltrexone and nalmefene) of AUD.
DESIGN
A nation-wide, register-based cohort study.
SETTING
Sweden.
PARTICIPANTS
All residents aged 16-64 years living in Sweden with registered first-time treatment contact due to AUD from July 2006 to December 2016 (n = 125 556, 62.5% men) were identified from nation-wide registers.
MEASUREMENTS
The main outcome was hospitalization due to AUD. The secondary outcomes were hospitalization due to any cause, alcohol-related somatic causes, as well as work disability (sickness absence or disability pension), and death. Mortality was analysed with between-individual analysis using a traditional multivariate-adjusted Cox hazards regression model. Recurrent outcomes, such as hospitalization-based events and work disability, were analysed with within-individual analyses to eliminate selection bias.
FINDINGS
Naltrexone combined with acamprosate [hazard ratio (HR) = 0.74; 95% confidence interval (CI) = 0.61-0.89], combined with disulfiram (HR = 0.76, 95% CI = 0.60-0.96) and as monotherapy (HR = 0.89, 95% CI = 0.81-0.97) was associated with a significantly lower risk of AUD-hospitalization compared with no use of AUD medication. Similar results were found for risk of hospitalization due to any cause. Benzodiazepine use and acamprosate monotherapy were associated with an increased risk of AUD-hospitalization (HR = 1.18, 95% CI = 1.14-1.22 and HR = 1.10, 95% CI = 1.04-1.17, respectively). No statistically significant effects were found for work disability or mortality.
CONCLUSIONS
Naltrexone as monotherapy and when combined with disulfiram and acamprosate appears to be associated with lower risk of hospitalization due to any and alcohol-related causes, compared with no use of alcohol use disorder (AUD) medication. Acamprosate monotherapy and benzodiazepine use appear to be associated with increased risk of AUD-associated hospitalization.
Topics: Acamprosate; Alcohol Deterrents; Alcoholism; Cohort Studies; Female; Humans; Male; Naltrexone; Sweden
PubMed: 33394527
DOI: 10.1111/add.15384 -
BMC Gastroenterology Feb 2023Alcohol cessation is the cornerstone of treatment for alcohol-related cirrhosis. This study evaluated associations between medical conversations about alcohol use...
BACKGROUND
Alcohol cessation is the cornerstone of treatment for alcohol-related cirrhosis. This study evaluated associations between medical conversations about alcohol use disorder (AUD) treatment, AUD treatment engagement, and mortality.
METHODS
This retrospective cohort study included all patients with ICD-10 diagnosis codes for cirrhosis and AUD who were engaged in hepatology care in a single healthcare system in 2015. Baseline demographic, medical, liver disease, and AUD treatment data were assessed. AUD treatment discussions and initiation, alcohol cessation, and subsequent 5-year mortality were collected. Multivariable models were used to assess the factors associated with subsequent AUD treatment and 5-year mortality.
RESULTS
Among 436 patients with cirrhosis due to alcohol, 65 patients (15%) received AUD treatment at baseline, including 48 (11%) receiving behavioral therapy alone, 11 (2%) receiving pharmacotherapy alone, and 6 (1%) receiving both. Over the first year after a baseline hepatology visit, 37 patients engaged in AUD treatment, 51 were retained in treatment, and 14 stopped treatment. Thirty percent of patients had hepatology-documented AUD treatment recommendations and 26% had primary care-documented AUD treatment recommendations. Most hepatology (86%) and primary care (88%) recommendations discussed behavioral therapy alone. Among patients with ongoing alcohol use at baseline, AUD treatment one year later was significantly, independently associated with AUD treatment discussions with hepatology (adjusted odds ratio (aOR): 3.23, 95% confidence interval (CI): 1.58, 6.89) or primary care (aOR: 2.95; 95% CI: 1.44, 6.15) and negatively associated with having Medicaid insurance (aOR: 0.43, 95% CI: 0.18, 0.93). When treatment was discussed in both settings, high rates of treatment ensued (aOR: 10.72, 95% CI: 3.89, 33.52). Over a 5-year follow-up period, 152 (35%) patients died. Ongoing alcohol use, age, hepatic decompensation, and hepatocellular carcinoma were significantly associated with mortality in the final survival model.
CONCLUSION
AUD treatment discussions were documented in less than half of hepatology and primary care encounters in patients with alcohol-related cirrhosis, though such discussions were significantly associated with receipt of AUD treatment.
Topics: United States; Humans; Retrospective Studies; Alcoholism; Liver Cirrhosis, Alcoholic; Longitudinal Studies
PubMed: 36732709
DOI: 10.1186/s12876-023-02656-z -
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 -
The Application of Clinical Genetics 2019Genetics of alcohol addiction is currently a contradictive and complex field, where data in the most studies reflect methods' limitations rather than meaningful and...
Genetics of alcohol addiction is currently a contradictive and complex field, where data in the most studies reflect methods' limitations rather than meaningful and complementary results. In our review, we focus on the genetics of alcohol addiction, leaving genetics of acute alcohol intoxication out of the scope. A review of the literature on pharmacogenetic biomarkers development for the pharmacotherapy personalization reveals that today the evidence base concerning these biomarkers is still insufficient. In particular, now the researches with the design of randomized controlled trials and meta-analysis investigating the effect of the SNPs as biomarkers on the therapy efficacy are available for naltrexone only. For other medications, there are only a few studies in small samples. It decreases the possibilities to implement the pharmacogenetic algorithms for the pharmacotherapy personalization in patients with alcohol use disorders (AUD). In view of the importance of the precision approaches development not in addiction medicine only, but in other fields of medicine also to increase the efficacy and safety of the therapy, studies on pharmacogenetic biomarkers development for the medications used in patients with AUD (eg, naltrexone, disulfiram, nalmefene, acamprosate, etc.) remain relevant to this day.
PubMed: 31372024
DOI: 10.2147/TACG.S206745 -
Addiction & Health Oct 2019Among the three pharmacological agents available for alcohol de-addiction, acamprosate and naltrexone are considered anti-craving agents. Among these two, acamprosate is...
BACKGROUND
Among the three pharmacological agents available for alcohol de-addiction, acamprosate and naltrexone are considered anti-craving agents. Among these two, acamprosate is better tolerated, has low abuse potential, and is safe in overdose. But the mechanism of action of acamprosate still remains unclear.
CASE REPORT
This case report gives a description of a 46-year-old male patient diagnosed with alcohol dependence syndrome with prior admissions and failed treatments with naltrexone and baclofen. He developed skin reaction after relapsing with alcohol use while receiving acamprosate therapy. The severity of the adverse effects varied with the amount of alcohol consumed by the patient. This suggests the possibility of deterrent-like action of acamprosate in our patient. The symptoms reduced after abstinence from alcohol and the patient was continued on acamprosate and relapse prevention therapy (RPT).
CONCLUSION
Clinicians should consider the possible deterrent effect of acamprosate and manage such patients accordingly.
PubMed: 32206220
DOI: 10.22122/ahj.v11i4.248 -
Cold Spring Harbor Perspectives in... Nov 2021There are currently effective Food and Drug Administration (FDA)-approved therapies for alcohol, nicotine, and opioid use disorders. This article will review the...
There are currently effective Food and Drug Administration (FDA)-approved therapies for alcohol, nicotine, and opioid use disorders. This article will review the development of eight compounds used in the treatment of drug addiction with an emphasis on pharmacological mechanisms and the utility of preclinical animal models of addiction in therapeutic development. In contrast to these successes, animal research has identified a number of promising medications for the treatment of psychostimulant use disorder, none of which have proven to be clinically effective. A specific example of an apparently promising pharmacotherapeutic for cocaine that failed clinically will be examined to determine whether this truly represents a challenge to the predictive validity of current models of cocaine addiction. In addition, the development of promising cocaine use disorder therapeutics derived from animal research will be reviewed, with some discussion regarding how preclinical studies might be modified to better inform clinical outcomes.
Topics: Acamprosate; Alcohol Deterrents; Alcoholism; Bupropion; Central Nervous System Stimulants; Cocaine-Related Disorders; Drug Therapy; Humans; Naltrexone; Narcotic Antagonists; Nicotinic Agonists; Smoking Cessation Agents; Substance-Related Disorders; Varenicline
PubMed: 32601131
DOI: 10.1101/cshperspect.a040311 -
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