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Alcohol (Fayetteville, N.Y.) Feb 2022Alcohol addiction is a chronic relapsing disease that is progressive and has severe detrimental health outcomes. The use of natural products has become popular for the...
Alcohol addiction is a chronic relapsing disease that is progressive and has severe detrimental health outcomes. The use of natural products has become popular for the treatment of side effects of drugs and substance abuse. Linalool is a monoterpenoid that exhibits several effects on the central nervous system. Linalool was identified to have beneficial effects on different mechanisms that are relevant in drug addiction or substance use disorder. The primary aim of the present study was to evaluate the therapeutic effect of linalool on the rewarding properties of alcohol in mice. Conditioned place preference (CPP) was established by intraperitoneal (i.p.) injection of ethanol (2 g/kg) during an 8-day conditioning trial. The effects of acamprosate and linalool on the rewarding properties of ethanol were tested in mice who received linalool (12.5, 25, and 50 mg/kg, i.p.) and acamprosate (300 mg/kg, i.p.) 30 min before each ethanol injection. CPP was extinguished by repeated testing, throughout which conditioned mice were administered daily linalool. Mice were lastly examined for reinstatement provoked by i.p. administration of single low-dose ethanol (0.4 g/kg, i.p.). Treatment with linalool reduced the acquisition and reinstatement, and precipitated the extinction of ethanol-induced CPP in mice. Acquisition and reinstatement of alcohol-induced CPP were significantly reduced by acamprosate, which also precipitated extinction. Ethanol alone and the combination with linalool or acamprosate did not alter locomotor activity. The results of this study suggest that linalool may have pharmacological effects for the treatment of alcohol addiction. In addition, further investigation is required to fully explore the benefits and possible adverse effects of linalool on alcohol addiction.
Topics: Acyclic Monoterpenes; Animals; Conditioning, Classical; Ethanol; Extinction, Psychological; Mice; Monoterpenes; Reward
PubMed: 34800613
DOI: 10.1016/j.alcohol.2021.11.003 -
Journal of Substance Abuse Treatment Jan 2023Alcohol use disorder (AUD) represents the most prevalent addiction in the United States. Integration of AUD treatment in primary care settings would expand care access.... (Review)
Review
BACKGROUND
Alcohol use disorder (AUD) represents the most prevalent addiction in the United States. Integration of AUD treatment in primary care settings would expand care access. The objective of this scoping review is to examine models of AUD treatment in primary care that include pharmacotherapy (acamprosate, disulfiram, naltrexone).
METHODS
The team undertook a search across MEDLINE, PsycINFO, CINAHL, the Cochrane Central Register of Controlled Trials, and Web of Science on May 21, 2021. Eligibility criteria included: patient population ≥ 18 years old, primary care-based setting, US-based study, presence of an intervention to promote AUD treatment, and prescription of FDA-approved AUD pharmacotherapy. Study design was limited to controlled trials and observational studies. We assessed study bias using a modified Oxford Centre for Evidence-based Medicine Rating Framework quality rating scheme.
RESULTS
The qualitative synthesis included forty-seven papers, representing 25 primary studies. Primary study sample sizes ranged from 24 to 830,825 participants and many (44 %) were randomized controlled trials. Most studies (80 %) included a nonpharmacologic intervention for AUD: 56 % with brief intervention, 40 % with motivational interviewing, and 12 % with motivational enhancement therapy. A plurality of studies (48 %) included mixed pharmacologic interventions, with administration of any combination of naltrexone, acamprosate, and/or disulfiram. Of the 47 total studies included, 68 % assessed care initiation and engagement. Fewer studies (15 %) explored practices surrounding screening for or diagnosing AUD. Outcome measures included receipt of pharmacotherapy and alcohol consumption, which about half of studies included (53 % and 51 %, respectively). Many of these outcomes showed significant findings in favor of integrated care models for AUD.
CONCLUSIONS
The integration of AUD pharmacotherapy in primary care settings may be associated with improved process and outcome measures of care. Future research should seek to understand the varied experiences across care integration models.
Topics: Humans; United States; Adolescent; Alcoholism; Acamprosate; Naltrexone; Disulfiram; Alcohol Drinking; Primary Health Care; Randomized Controlled Trials as Topic
PubMed: 36332528
DOI: 10.1016/j.jsat.2022.108919 -
The Medical Letter on Drugs and... Dec 2021
Topics: Alcoholism; Ethanol; Humans; Pharmaceutical Preparations
PubMed: 35100235
DOI: No ID Found -
Alcohol Research : Current Reviews 2022This article is part of a Festschrift commemorating the 50th anniversary of the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Established in 1970, first as... (Review)
Review
This article is part of a Festschrift commemorating the 50th anniversary of the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Established in 1970, first as part of the National Institute of Mental Health and later as an independent institute of the National Institutes of Health, NIAAA today is the world's largest funding agency for alcohol research. In addition to its own intramural research program, NIAAA supports the entire spectrum of innovative basic, translational, and clinical research to advance the diagnosis, prevention, and treatment of alcohol use disorder and alcohol-related problems. To celebrate the anniversary, NIAAA hosted a 2-day symposium, "Alcohol Across the Lifespan: 50 Years of Evidence-Based Diagnosis, Prevention, and Treatment Research," devoted to key topics within the field of alcohol research. This article is based on Dr. Mason's presentation at the event. NIAAA Director George F. Koob, Ph.D., serves as editor of the Festschrift.
Topics: United States; Humans; Alcoholism; National Institute on Alcohol Abuse and Alcoholism (U.S.); Alcohol Drinking; Alcohol-Related Disorders; National Institutes of Health (U.S.); Alcohol Deterrents; Naltrexone
PubMed: 36320345
DOI: 10.35946/arcr.v42.1.11 -
Journal of General Internal Medicine Jul 2021Alcohol use disorder (AUD) imposes a high mortality and economic burden. Effective treatment is available, though underutilized.
BACKGROUND
Alcohol use disorder (AUD) imposes a high mortality and economic burden. Effective treatment is available, though underutilized.
OBJECTIVE
Describe trends in AUD pharmacotherapy, variation in prescribing, and associated patient factors.
DESIGN
Retrospective cohort using electronic health records from 2010 to 2019.
PARTICIPANTS
Primary care patients from 39 clinics in Ohio and Florida with diagnostic codes for alcohol dependence or abuse plus social history indicating alcohol use. PCPs in family or internal medicine with at least 20 AUD patients.
MAIN MEASURES
Pharmacotherapy for AUD (naltrexone, acamprosate, and disulfiram), abstinence from alcohol, patient demographics, and comorbidities. Generalized linear mixed models were used to identify patient factors associated with prescriptions and the association of pharmacotherapy with abstinence.
KEY RESULTS
We identified 13,250 patients; average age was 54 years, 66.9% were male, 75.0% were White, and median household income was $51,776 per year. Over 10 years, the prescription rate rose from 4.4 to 5.6%. Patients who were Black (aOR 0.74; 95% CI 0.58, 0.94) and insured by Medicare versus commercial insurance (aOR 0.61; 95% CI 0.48, 0.78) were less likely to be treated. Higher median household income ($10,000 increment, aOR 1.06; 95% CI 1.03, 1.10) and Medicaid versus commercial insurance (aOR 1.52; 95% CI 1.24, 1.87) were associated with treatment. Receiving pharmacotherapy was associated with subsequent documented abstinence from alcohol (aOR 1.60; 95% CI 1.33, 1.92). We identified 236 PCPs. The average prescription rate was 3.6% (range 0 to 24%). The top decile prescribed to 14.6% of their patients. The bottom 4 deciles had no prescriptions. Family physicians had higher rates of pharmacotherapy than internists (OR 1.50; 95% CI 1.21, 1.85).
CONCLUSIONS
Medications for AUD are infrequently prescribed, but there is considerable variation among PCPs. Increasing the use of pharmacotherapy by non-prescribers may increase abstinence from alcohol.
Topics: Aged; Alcoholism; Florida; Humans; Male; Medicare; Middle Aged; Ohio; Primary Health Care; Retrospective Studies; United States
PubMed: 33515195
DOI: 10.1007/s11606-020-06454-1 -
Handbook of Experimental Pharmacology 2020Compared to other medical disorders, including other brain diseases, the number of medications approved for alcohol use disorder (AUD) is very small. Disulfiram,... (Review)
Review
Compared to other medical disorders, including other brain diseases, the number of medications approved for alcohol use disorder (AUD) is very small. Disulfiram, naltrexone (oral and long-acting), and acamprosate are approved by the US Food and Drug Administration (FDA) to treat patients with AUD. These medications are also approved in other countries, including in Europe, where the European Medicines Agency (EMA) also approved nalmefene for AUD. Furthermore, baclofen was recently approved for AUD in France. These approved medications have small effect sizes, which are probably the consequence of the fact that they only work for some patients, yet a personalized approach to match the right medication with the right patient is still in its infancy. Therefore, research is needed to expand the armamentarium of medications that clinicians can use to treat their patients, as well as to better develop personalized approaches. This book chapter reviews other medications, beyond those approved by the FDA, that have shown efficacy in clinical trials, as well as medications which are still in the early stages of evaluation in human studies.
Topics: Acamprosate; Alcohol Deterrents; Alcoholism; Disulfiram; Drug Development; Humans; Naltrexone
PubMed: 31628604
DOI: 10.1007/164_2019_295 -
Hepatology (Baltimore, Md.) Feb 2024The role of medications for alcohol use disorder (MAUD) in patients with cirrhosis is not well established. Evidence on the efficacy and safety of these drugs in these... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
The role of medications for alcohol use disorder (MAUD) in patients with cirrhosis is not well established. Evidence on the efficacy and safety of these drugs in these patients is scarce.
APPROACH AND RESULTS
We performed a systematic review and meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol guidelines on the efficacy of MAUD in patients with cirrhosis. A search was conducted in PubMed, Embase, and Scopus, including all studies until May 2022. The population was defined as patients with AUD and cirrhosis. The primary outcome was alcohol abstinence. Safety was a secondary outcome. We performed a random-effect analysis and expressed the results as relative risk of alcohol consumption. Heterogeneity was measured by I2 . Out of 4095 unique references, 8 studies on 4 different AUD treatments [baclofen (n = 6), metadoxine (n = 1), acamprosate (n = 1), and fecal microbiota transplant (n = 1)] in a total of 794 patients were included. Four were cohort studies, and 4 were RCTs. Only RCTs were included in the meta-analysis. MAUD was associated with a reduced rate of alcohol consumption [relative risk = 0.68 (CI: 0.48-0.97), P = 0.03], increasing alcohol abstinence by 32% compared to placebo or standard treatment, despite high heterogeneity ( I2 = 67%). Regarding safety, out of 165 serious adverse events in patients treated with MAUD, only 5 (3%) were possibly or probably related to study medications.
CONCLUSION
MAUD in patients with cirrhosis is effective in promoting alcohol abstinence and has a good safety profile. Larger studies on the effects of MAUD are needed, especially in patients with advanced liver disease.
Topics: Humans; Alcoholism; Alcohol Drinking; Acamprosate; Liver Cirrhosis, Alcoholic; Liver Cirrhosis
PubMed: 37625154
DOI: 10.1097/HEP.0000000000000570 -
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