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Current Opinion in Pharmacology Feb 2022Alcohol contributes to more than 5% of global mortality, and causes more than half of all liver-related deaths. The Alcohol Use Disorders Identification Test (AUDIT) can... (Review)
Review
Alcohol contributes to more than 5% of global mortality, and causes more than half of all liver-related deaths. The Alcohol Use Disorders Identification Test (AUDIT) can be used to detect those patients with hazardous drinking and alcohol dependence who will benefit from psychosocial and pharmacological alcohol treatment. Psychosocial treatments range from brief interventions and cognitive behavioral therapy, to experimental neuropsychological treatments. Psychosocial intervention can be combined with acamprosate or naltrexone as first line pharmacological treatments. For patients with liver disease, abstinence increases survival and is therefore an important treatment goal. Acamprosate is a good choice, as it prevents relapse to drinking with a number needed to treat of 12. There are no reports indicating high risks of liver toxicity for acamprosate or naltrexone, but evidence is scarce. We recommend vigorous screening for alcohol use disorder in liver disease patients, followed by psychosocial intervention and complemented by pharmaceutical therapy.
Topics: Acamprosate; Alcohol Deterrents; Alcoholism; Humans; Liver Diseases; Naltrexone; Narcotic Antagonists; Treatment Outcome
PubMed: 34999372
DOI: 10.1016/j.coph.2021.11.012 -
Mayo Clinic Proceedings Sep 2020Pathologic alcohol use affects more than 2 billion people and accounts for nearly 6% of all deaths worldwide. There are three medications approved for the treatment of... (Review)
Review
Pathologic alcohol use affects more than 2 billion people and accounts for nearly 6% of all deaths worldwide. There are three medications approved for the treatment of alcohol use disorder by the US Food and Drug Administration (FDA): disulfiram, naltrexone (oral and long-acting injectable), and acamprosate. Of growing interest is the use of anticonvulsants for the treatment of alcohol use disorder, although currently none are FDA approved for this indication. Baclofen, a γ-aminobutyric acid B receptor agonist used for spasticity and pain, received temporary approval for alcohol use disorder in France. Despite effective pharmacotherapies, less than 9% of patients who undergo any form of alcohol use disorder treatment receive pharmacotherapies. Current evidence does not support the use of pharmacogenetic testing for treatment individualization. The objective of this review is to provide knowledge on practice parameters for evidenced-based pharmacologic treatment approaches in patients with alcohol use disorder.
Topics: Acamprosate; Alcohol Deterrents; Alcoholism; Anticonvulsants; Disulfiram; Evidence-Based Medicine; Humans; Mass Screening; Naltrexone; Off-Label Use; Practice Guidelines as Topic
PubMed: 32446635
DOI: 10.1016/j.mayocp.2020.01.030 -
Psychopharmacology May 2021Proton magnetic resonance spectroscopy (H-MRS) is a cross-species neuroimaging technique that can measure concentrations of several brain metabolites, including... (Review)
Review
RATIONALE
Proton magnetic resonance spectroscopy (H-MRS) is a cross-species neuroimaging technique that can measure concentrations of several brain metabolites, including glutamate and GABA. This non-invasive method has promise in developing centrally acting drugs, as it can be performed repeatedly within-subjects and be used to translate findings from the preclinical to clinical laboratory using the same imaging biomarker.
OBJECTIVES
This review focuses on the utility of single-voxel H-MRS in developing novel glutamatergic or GABAergic drugs for the treatment of psychiatric disorders and includes research performed in rodent models, healthy volunteers and patient cohorts.
RESULTS
Overall, these studies indicate that H-MRS is able to detect the predicted pharmacological effects of glutamatergic or GABAergic drugs on voxel glutamate or GABA concentrations, although there is a shortage of studies examining dose-related effects. Clinical studies have applied H-MRS to better understand drug therapeutic mechanisms, including the glutamatergic effects of ketamine in depression and of acamprosate in alcohol dependence. There is an emerging interest in identifying patient subgroups with 'high' or 'low' brain regional H-MRS glutamate levels for more targeted drug development, which may require ancillary biomarkers to improve the accuracy of subgroup discrimination.
CONCLUSIONS
Considerations for future research include the sensitivity of single-voxel H-MRS in detecting drug effects, inter-site measurement reliability and the interpretation of drug-induced changes in H-MRS metabolites relative to the known pharmacological molecular mechanisms. On-going technological development, in single-voxel H-MRS and in related complementary techniques, will further support applications within CNS drug discovery.
Topics: Acamprosate; Alcoholism; Brain; Central Nervous System Agents; Drug Development; Glutamic Acid; Humans; Ketamine; Neuroimaging; Proton Magnetic Resonance Spectroscopy; Reproducibility of Results
PubMed: 31486875
DOI: 10.1007/s00213-019-05344-7 -
Current Geriatrics Reports 2021The prevalence of alcohol use disorder (AUD) among older adults in the United States is rising, but remains underdiagnosed, underreported, and inadequately managed. This... (Review)
Review
PURPOSE OF REVIEW
The prevalence of alcohol use disorder (AUD) among older adults in the United States is rising, but remains underdiagnosed, underreported, and inadequately managed. This review highlights the medical, social, and cultural factors of AUD in older adults and provides guidelines for its screening, evaluation, and management.
RECENT FINDINGS
The COVID-19 pandemic has created additional challenges and barriers to care, as older adults may have disproportionate worsening of anxiety, depression, and substance use resulting from increased isolation related to physical distancing and shelter-in-place guidelines.
SUMMARY
All older adults should be routinely screened for AUD with standardized screening tools. If a patient's screening results are positive, a clinician should conduct a brief assessment, which may be supplemented by laboratory tests. Most older adults at risk for alcohol misuse do not need specialized SUD treatment, but most can benefit from Screening, Brief Intervention, and Referral to Treatment (SBIRT) to prevent substance misuse before it occurs. Medications for the treatment of AUD in older adults include naltrexone, acamprosate, disulfiram, gabapentin and topiramate. Psychosocial treatments, including mutual help groups, are equally important.
PubMed: 34336549
DOI: 10.1007/s13670-021-00359-5 -
Addiction Biology Sep 2022Acamprosate (Campral® - calcium-bis[N-acetylhomotaurinate]) is one of few available pharmacotherapies for individuals suffering from alcohol use disorder. Previously,...
Acamprosate (Campral® - calcium-bis[N-acetylhomotaurinate]) is one of few available pharmacotherapies for individuals suffering from alcohol use disorder. Previously, we suggested that acamprosate reduces ethanol intake by increasing dopamine in the nucleus accumbens (nAc), thereby partly substituting for alcohol's dopamine releasing effect. An experimental study suggested the calcium moiety of acamprosate to be the active component of the drug and to mediate the relapse preventing effect. The aim of the present study was to, by means of reversed in vivo microdialysis, elucidate if the dopamine elevating properties of acamprosate are mediated by N-acetylhomotaurine or by the calcium moiety. Male rats were equipped with a microdialysis probe in the nAc and received acute local treatment with regular acamprosate (CaAcamp 0.5 mM), calcium chloride (CaCl 0.5 mM), sodium acamprosate (NaAcamp 0.5-1 mM), the glycine receptor (GlyR) antagonist strychnine (Stry 20 μM), or vehicle. In all experiments, extracellular levels of dopamine and taurine were examined. We found that local perfusion with both CaAcamp and CaCl increased dopamine levels in a GlyR-dependent manner. NaAcamp did not influence dopamine levels, but concomitant administration with CaCl resulted in an additive dopamine output compared to the drugs administrated alone. We also found CaAcamp and the combination of CaCl and NaAcamp to increase accumbal taurine levels, suggesting that CaAcamp may act indirectly on GlyRs via taurine release. The present results indicate that both N-acetylhomotaurine and the calcium moiety of acamprosate have dopamine elevating properties within the nAc and that, in this respect, these substances are beneficial in combination.
Topics: Acamprosate; Animals; Calcium; Calcium Chloride; Dopamine; Male; Microdialysis; Nucleus Accumbens; Rats; Rats, Wistar; Receptors, Glycine; Sodium; Taurine
PubMed: 36001425
DOI: 10.1111/adb.13224 -
Current Opinion in Psychiatry Jul 2019Only a few pharmacological treatments are available for treating alcohol use disorders (AUDs). Disulfiram, naltrexone and acamprosate are Food and Drug Administration... (Review)
Review
PURPOSE OF REVIEW
Only a few pharmacological treatments are available for treating alcohol use disorders (AUDs). Disulfiram, naltrexone and acamprosate are Food and Drug Administration (FDA)-approved and nalmefene is EMA-approved in European Union. Off-label medications, such as baclofen, gabapentin, ondansetron and topiramate are medications commonly prescribed for the treatment of AUD. The aim of this review is to give an update on recent randomized controlled trials (RCTs) and reviews evaluating pharmacological treatment for AUD.
RECENT FINDINGS
A literature search was conducted for pharmacological treatment for alcohol use disorder, published from January 2017 to January 2019. An additional search from two ongoing-study databases was performed. A total of 13 studies, 11 reviews and 7 on-going clinical trials were identified. Interest in studying baclofen as a treatment for AUD was greater compared with other medications, yet with inconclusive results. Three new RCTs of first-line medication naltrexone showed reduction in drinking.
SUMMARY
Three new published RCTs focus on baclofen and naltrexone. These results are consistent with old findings demonstrating that naltrexone reduces heavy drinking. Several RCT on baclofen do not support the use of baclofen for treatment of AUD. Encouraging results have been reported for topiramate, gabapentin and also varenicline, which might be useful in patients with comorbid nicotine dependence.
Topics: Acamprosate; Alcoholism; Antidepressive Agents; Baclofen; Cholinergic Agonists; Disulfiram; Gabapentin; Humans; Naltrexone; Ondansetron; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 30973369
DOI: 10.1097/YCO.0000000000000512 -
Pharmacology & Therapeutics Dec 2022Alcohol Use Disorder (AUD) is a multifaceted relapsing disorder that is commonly comorbid with psychiatric disorders, including anxiety. Alcohol exposure produces a... (Review)
Review
Alcohol Use Disorder (AUD) is a multifaceted relapsing disorder that is commonly comorbid with psychiatric disorders, including anxiety. Alcohol exposure produces a plethora of effects on neurobiology. Currently, therapeutic strategies are limited, and only a few treatments - disulfiram, acamprosate, and naltrexone - are available. Given the complexity of this disorder, there is a great need for the identification of novel targets to develop new pharmacotherapy. The GABAergic system, the primary inhibitory system in the brain, is one of the well-known targets for alcohol and is responsible for the anxiolytic effects of alcohol. Interestingly, GABAergic neurotransmission is fine-tuned by neuroactive steroids that exert a regulatory role on several endocrine systems involved in neuropsychiatric disorders including AUD. Mounting evidence indicates that alcohol alters the biosynthesis of neurosteroids, whereas acute alcohol increases and chronic alcohol decreases allopregnanolone levels. Our recent work highlighted that chronic alcohol-induced changes in neurosteroid levels are mediated by epigenetic modifications, e.g., DNA methylation, affecting key enzymes involved in neurosteroid biosynthesis. These changes were associated with changes in GABA receptor subunit expression, suggesting an imbalance between excitatory and inhibitory signaling in AUD. This review will recapitulate the role of neurosteroids in the regulation of the neuroendocrine system, highlight their role in the observed allostatic load in AUD, and develop a framework from mechanisms to potential pharmacotherapy.
Topics: Humans; Pregnanolone; Neurosteroids; Alcoholism; Receptors, GABA-A; Anxiety; Ethanol
PubMed: 36323379
DOI: 10.1016/j.pharmthera.2022.108299 -
The Psychiatric Clinics of North America Jun 2020This article reviews some of the recent discoveries about how neurobiological processes contribute to the understanding and treatment of substance use disorders.... (Review)
Review
This article reviews some of the recent discoveries about how neurobiological processes contribute to the understanding and treatment of substance use disorders. Particular focus is given to cannabis, opioids, and designer drugs. Important areas addressed include triggers and cravings, the central roles of dopamine and stress, and the endocannabinoid system. Clinical relevance of these findings for withdrawal management and relapse prevention is discussed. Also highlighted are issues related to the opioid epidemic and consequences both of continuing federal prohibition of cannabis as well as its state-by-state relaxation.
Topics: Analgesics, Opioid; Craving; Humans; Opioid-Related Disorders; Substance Withdrawal Syndrome; Substance-Related Disorders
PubMed: 32439023
DOI: 10.1016/j.psc.2020.02.011 -
American Family Physician May 2024Substance misuse and substance use disorder continue to be major causes of morbidity and mortality, and family physicians are well positioned to provide evidence-based... (Review)
Review
Substance misuse and substance use disorder continue to be major causes of morbidity and mortality, and family physicians are well positioned to provide evidence-based prevention and management for these conditions. Of people 12 years and older, 13% reported using a nonprescribed controlled substance in the past month, and 24% had at least one episode of binge drinking of alcohol, defined as five or more drinks for men and four or more drinks for women on one occasion. Benzodiazepines are used by 12% of the U.S. population. Clinicians should incorporate standardized screening and brief intervention for use of alcohol and other substances into routine care of adult patients, as well as referral to specialized treatment services when indicated. Use of nonstigmatizing, person-first language has been shown to positively affect care for patients with substance use disorders. Alcohol screening and brief intervention have been shown to reduce excessive drinking by 40% in patients at 6 months postintervention. Office-based treatment of alcohol use disorder with medications approved by the U.S. Food and Drug Administration, such as acamprosate and naltrexone, remains underutilized, presenting another opportunity for family physicians to positively affect the health of their patients and communities. With elimination of the X-waiver, any clinician with Schedule III prescriptive authority can treat opioid use disorder with buprenorphine in their office-based practice. Opioid overdose education and naloxone coprescribing are other tools family physicians can employ to combat the overdose crisis.
Topics: Humans; Primary Health Care; Substance-Related Disorders; Adult; Female; United States; Male
PubMed: 38804757
DOI: No ID Found -
International Review of Neurobiology 2024Repurposing drugs for the treatment of alcohol dependence involves the use of drugs that were initially developed for other conditions, but have shown promise in... (Review)
Review
Repurposing drugs for the treatment of alcohol dependence involves the use of drugs that were initially developed for other conditions, but have shown promise in reducing alcohol use or preventing relapse. This approach can offer a more cost-effective and time-efficient alternative to developing new drugs from scratch. Currently approved medications for alcohol use disorder (AUD) include acamprosate, disulfiram, naltrexone, nalmefene, baclofen, and sodium oxybate. Acamprosate was developed specifically for AUD, while disulfiram's alcohol-deterrent effects were discovered incidentally. Naltrexone and nalmefene were originally approved for opioids but found secondary applications in AUD. Baclofen and sodium oxybate were repurposed from neurological conditions. Other drugs show promise. Topiramate and zonisamide, anticonvulsants, demonstrate efficacy in reducing alcohol consumption. Another anticonvulsant, gabapentin has been disappointing overall, except in cases involving alcohol withdrawal symptoms. Varenicline, a nicotinic receptor agonist, benefits individuals with less severe AUD or concurrent nicotine use. Ondansetron, a 5-HT3 antagonist, has potential for early-onset AUD, especially when combined with naltrexone. Antipsychotic drugs like aripiprazole and quetiapine have limited efficacy. Further investigation is needed for potential repurposing of α1 adrenergic receptor antagonists prazosin and doxazosin, glucocorticoid receptor antagonist mifepristone, the phosphodiesterase inhibitor Ibudilast, the cysteine prodrug N-acetylcysteine, and the OX1R and OX2R blocker Suvorexant. This review supports repurposing drugs as an effective strategy for expanding treatment options for AUD.
Topics: Humans; Alcoholism; Acamprosate; Naltrexone; Disulfiram; Sodium Oxybate; Baclofen; Drug Repositioning; Substance Withdrawal Syndrome; Alcohol Drinking
PubMed: 38555115
DOI: 10.1016/bs.irn.2024.02.002