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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 -
Der Nervenarzt Jan 2021So far few medications are approved for prophylactic treatment of alcohol dependence relapse. Apart from disulfiram, which is no longer marketed in Germany, the opioid... (Review)
Review
So far few medications are approved for prophylactic treatment of alcohol dependence relapse. Apart from disulfiram, which is no longer marketed in Germany, the opioid antagonists naltrexone, nalmefene and the putative glutamate antagonist acamprosate are approved. In some other countries, baclofen and gamma-hydroxybutyrate (GHB) are licensed. Possible other drugs of interest for prophylaxis of alcohol dependence relapse are vareniclin, gabapentin, and topiramate, but so far none of them have received approval. In the light of the currently running revision of the German guidelines for the diagnosis and treatment of alcohol related disorders, an update on the pharmacotherapy of alcohol dependence is presented.
Topics: Acamprosate; Alcohol Deterrents; Alcoholism; Germany; Humans; Naltrexone; Narcotic Antagonists; Taurine
PubMed: 32696076
DOI: 10.1007/s00115-020-00954-5 -
Frontiers in Pharmacology 2020Selective serotonin reuptake inhibitors (SSRIs) are a standard of care for the pharmacotherapy of patients suffering from Major Depressive Disorder (MDD). However, only... (Review)
Review
Selective serotonin reuptake inhibitors (SSRIs) are a standard of care for the pharmacotherapy of patients suffering from Major Depressive Disorder (MDD). However, only one-half to two-thirds of MDD patients respond to SSRI therapy. Recently, a "multiple omics" research strategy was applied to identify genetic differences between patients who did and did not respond to SSRI therapy. As a first step, plasma metabolites were assayed using samples from the 803 patients in the PGRN-AMPS SSRI MDD trial. The metabolomics data were then used to "inform" genomics by performing a genome-wide association study (GWAS) for plasma concentrations of the metabolite most highly associated with clinical response, serotonin (5-HT). Two genome-wide or near genome-wide significant single nucleotide polymorphism (SNP) signals were identified, one that mapped near the gene and another across the gene, both genes that are highly expressed in the brain. Knocking down TSPAN5 and ERICH3 resulted in decreased 5-HT concentrations in neuroblastoma cell culture media and decreased expression of enzymes involved in 5-HT biosynthesis and metabolism. Functional genomic studies demonstrated that ERICH3 was involved in clathrin-mediated vesicle formation and was an ethanol-responsive gene that may be a marker for response to acamprosate pharmacotherapy of alcohol use disorder (AUD), a neuropsychiatric disorder highly co-morbid with MDD. In parallel studies, kynurenine was the plasma metabolite most highly associated with MDD symptom severity and application of a metabolomics-informed pharmacogenomics approach identified and as genes associated with variation in plasma kynurenine levels. Both genes also contributed to kynurenine-related inflammatory pathways. Finally, a multiply replicated predictive algorithm for SSRI clinical response with a balanced predictive accuracy of 76% (compared with 56% for clinical data alone) was developed by including the SNPs in , , and . In summary, application of a multiple omics research strategy that used metabolomics to inform genomics, followed by functional genomic studies, identified novel genes that influenced monoamine biology and made it possible to develop a predictive algorithm for SSRI clinical outcomes in MDD. A similar pharmaco-omic research strategy might be broadly applicable for the study of other neuropsychiatric diseases and their drug therapy.
PubMed: 33510640
DOI: 10.3389/fphar.2020.614048 -
The Annals of Otology, Rhinology, and... Nov 2020Tinnitus is a common and distressing otologic symptom, with various probable pathophysiologic mechanisms, such as an imbalance between excitatory and inhibitory... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
Tinnitus is a common and distressing otologic symptom, with various probable pathophysiologic mechanisms, such as an imbalance between excitatory and inhibitory mechanisms. Acamprosate, generally used to treat alcoholism, is a glutaminergic antagonist and GABA agonist suggested for treating tinnitus. Thus, we aimed to evaluate the efficacy and safety of acamprosate in the treatment of tinnitus.
METHODS
The current randomized-controlled trial study included 20 subjects with chronic tinnitus. After performing psycho-acoustic, psychometric and electrophysiological evaluations, all studied tinnitus subjects were randomly divided into two groups of acamprosate and placebo. The first group received oral acamprosate (two tablets of 333 mg/d, three times a day), whereas the second group was given placebo treatment (two tablets, three times a day). After the first 30 days, all evaluations were repeated for the studied groups just in the same manner before the study. Subsequently, the final results of each evaluation were compared together with the baseline values.
RESULTS
Nine studied subjects randomly received acamprosate, whereas eleven others received a placebo. There was no significant improvement in the psycho-acoustic tests, except a decrease was observed in the pitch match of tinnitus ( = .039). For those subjects who were receiving acamprosate, a significant reduction was observed in tinnitus handicap inventory ( = .006), tinnitus questionnaire scores ( = .007), and the visual analog scores ( = .007) compared to the placebo group. There was a significant reduction in Action Potential latency ( = .048) as well as an increase in the amplitude of distortion product otoacoustic emissions at 4 kHz ( = .048).
CONCLUSIONS
The study results indicated a subjective relief of tinnitus as well as some degree of the electrophysiological improvement at the level of the cochlear and the distal portion of the auditory nerve among the subjects who received the acamprosate.
CLINICAL TRIAL REGISTRATION CODE
IRCT2013121115751N1.
Topics: Acamprosate; Administration, Oral; Adolescent; Adult; Alcohol Deterrents; Audiometry, Pure-Tone; Chronic Disease; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Otoacoustic Emissions, Spontaneous; Retrospective Studies; Tinnitus; Young Adult
PubMed: 32500717
DOI: 10.1177/0003489420930773 -
Physiology & Behavior Feb 2023Despite the teratogenic effects of alcohol, little is known about the safety of pharmacotherapies such as acamprosate for the treatment of alcohol use disorders in...
BACKGROUND
Despite the teratogenic effects of alcohol, little is known about the safety of pharmacotherapies such as acamprosate for the treatment of alcohol use disorders in pregnancy. The aims of this study were to investigate, in a mouse model, the effects of maternally administered acamprosate on maternal and neonatal health, offspring neurodevelopment and behaviour, as well as examine whether acamprosate reduces the neurological harm associated with alcohol consumption in pregnancy.
METHODS
Dams were randomly allocated to one of four treatment groups: (i) control (water), (ii) acamprosate (1.6 g/L), (iii) alcohol (5% v/v) or (iv) acamprosate and alcohol (1.6 g/L; 5% v/v ethanol) and exposed from 2-weeks pre-pregnancy until postpartum day 7. Gestational outcomes including litter size and sex ratio were assessed, in addition to early-life markers of neurodevelopment. At 8 weeks of age, motor coordination, anxiety, locomotion, and memory of the adult offspring were also examined.
RESULTS
Exposure to acamprosate did not affect maternal and birth outcomes (mating success, gestational weight gain, litter size, sex ratio), neonatal outcomes (head and body length, postnatal weight) or neurodevelopmental markers (righting reflex and negative geotaxis). Acamprosate exposure did not affect offspring motor control, locomotion or anxiety, however the effects on short-term memory remain uncertain. Prenatal alcohol exposed offspring exhibited various alterations, such as lower postnatal weight, smaller head (p = 0.04) and body lengths (p = 0.046) at postnatal day 70 (males only), increased negative geotaxis speed (p = 0.03), an increased time spent in the inner zone of the open field (p = 0.02). Acamprosate mitigated the effects of alcohol for negative geotaxis at postnatal day 7 (p = 0.01) and female offspring weight at postnatal day 70 (p = 0.03).
CONCLUSIONS
Overall, we show that prenatal acamprosate exposure was not associated with poor maternal or neonatal health outcomes or impaired neurodevelopment and behaviour. However, acamprosate's effects on short-term memory remain uncertain. We present preliminary evidence to suggest acamprosate displayed some neuroprotective effects against damage caused by in utero alcohol exposure.
Topics: Pregnancy; Mice; Animals; Male; Humans; Female; Alcoholism; Acamprosate; Prenatal Exposure Delayed Effects; Reproduction; Ethanol
PubMed: 36427542
DOI: 10.1016/j.physbeh.2022.114037 -
Frontiers in Pharmacology 2022Acamprosate is an anti-craving drug used in alcohol use disorder (AUD) pharmacotherapy. However, only a subset of patients achieves optimal treatment outcomes. The...
Acamprosate is an anti-craving drug used in alcohol use disorder (AUD) pharmacotherapy. However, only a subset of patients achieves optimal treatment outcomes. The identification of predictive biomarkers of acamprosate treatment response in patients with AUD would be a substantial advance in addiction medicine. We designed this study to use proteomics data as a quantitative biological trait as a step toward identifying inflammatory modulators that might be associated with acamprosate treatment outcomes. The NIAAA-funded Mayo Clinic Center for the Individualized Treatment of Alcoholism study had previously recruited 442 AUD patients who received 3 months of acamprosate treatment. However, only 267 subjects returned for the 3-month follow-up visit and, as a result, had treatment outcome information available. Baseline alcohol craving intensity was the most significant predictor of acamprosate treatment outcomes. We performed plasma proteomics using the Olink target 96 inflammation panel and identified that baseline plasma TNF superfamily member 10 (TNFSF10) concentration was associated with alcohol craving intensity and variation in acamprosate treatment outcomes among AUD patients. We also performed RNA sequencing using baseline peripheral blood mononuclear cells from AUD patients with known acamprosate treatment outcomes which revealed that inflammation-related pathways were highly associated with relapse to alcohol use during the 3 months of acamprosate treatment. These observations represent an important step toward advancing our understanding of the pathophysiology of AUD and molecular mechanisms associated with acamprosate treatment response. In conclusion, applying omics-based approaches may be a practical approach for identifying biologic markers that could potentially predict alcohol craving intensity and acamprosate treatment response.
PubMed: 36120372
DOI: 10.3389/fphar.2022.986238 -
Nordic Journal of Psychiatry Jul 2022Many patients with alcohol use disorders are challenged by cravings leading to repeated relapses. Both cue exposure therapy (CET) and acamprosate target alcohol cravings... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
Many patients with alcohol use disorders are challenged by cravings leading to repeated relapses. Both cue exposure therapy (CET) and acamprosate target alcohol cravings and are often combined (CET + acamprosate). The main aim of this study was to investigate whether aftercare treatment consisting of CET combined with acamprosate is equivalent to (A) CET as monotherapy, (B) aftercare as usual (AAU) as monotherapy or (C) AAU combined with acamprosate.
METHODS
Patients were randomized to receive either CET with urge-specific coping skills (USCS) as aftercare or AAU. Acamprosate prescription data were extracted from patient case records. Alcohol consumption, cravings, and USCS were assessed at pre-aftercare, post-aftercare, and 6-month follow-up.
RESULTS
Overall, patients increased their alcohol consumption during and following aftercare treatment, thereby relapsing despite any treatment. However, CET + acamprosate achieved greater abstinence compared to AAU + acamprosate at follow-up (=.047). CET + acamprosate also reduced number of drinking days (=.020) and number of days with excessive drinking (=.020) at post-aftercare, when compared to AAU monotherapy. CET monotherapy increased sensible drinking at post-aftercare compared to AAU monotherapy (=.045) and AAU + acamprosate (=.047). Only CET monotherapy showed improvement in cravings, when compared to AAU at follow-up (mean urge level: =.032; peak urge level: =.014).
CONCLUSION
The study showed that CET both as monotherapy and combined with acamprosate was superior to AAU monotherapy and AAU + acamprosate in reducing alcohol consumption. Only CET + acamprosate was capable of reducing alcohol consumption in the longer term, indicating that anti-craving medication may not impede CET from exerting an effect on alcohol consumption. ClinicalTrials.gov ID: NCT02298751 (24/11-2014).
Topics: Acamprosate; Aftercare; Alcoholism; Cues; Humans; Implosive Therapy; Secondary Prevention
PubMed: 34622734
DOI: 10.1080/08039488.2021.1985169 -
Cells Dec 2020Musculoskeletal injuries represent a challenging medical problem. Although the skeletal muscle is able to regenerate and recover after injury, the process engaged with...
Musculoskeletal injuries represent a challenging medical problem. Although the skeletal muscle is able to regenerate and recover after injury, the process engaged with conservative therapy can be inefficient, leading to a high re-injury rate. In addition, the formation of scar tissue implies an alteration of mechanical properties in muscle. There is still a need for new treatments of the injured muscle. NeuroHeal may be one option. Published studies demonstrated that it reduces muscle atrophy due to denervation and disuse. The main objective of the present work was to assess the potential of NeuroHeal to improve muscle regeneration after traumatic injury. Secondary objectives included characterizing the effect of NeuroHeal treatment on satellite cell biology. We used a rat model of sport-induced injury in the gastrocnemius and analyzed the effects of NeuroHeal on functional recovery by means of electrophysiology and tetanic force analysis. These studies were accompanied by immunohistochemistry of the injured muscle to analyze fibrosis, satellite cell state, and fiber type. In addition, we used an in vitro model to determine the effect of NeuroHeal on myoblast biology and partially decipher its mechanism of action. The results showed that NeuroHeal treatment advanced muscle fiber recovery after injury in a preclinical model of muscle injury, and significantly reduced the formation of scar tissue. In vitro, we observed that NeuroHeal accelerated the formation of myotubes. The results pave the way for novel therapeutic avenues for muscle/tendinous disorders.
Topics: Acamprosate; Animals; Athletic Injuries; Cell Line; Drug Combinations; Male; Mice; Muscle Fibers, Skeletal; Muscle, Skeletal; Myoblasts; Neuroprotective Agents; Rats; Rats, Wistar; Recovery of Function; Regeneration; Ribavirin
PubMed: 33374379
DOI: 10.3390/cells10010022 -
Alcohol and Alcoholism (Oxford,... Sep 2022To understand service users' views and experiences of alcohol relapse prevention medication, views of a telephone behavioural modification intervention delivered by...
AIMS
To understand service users' views and experiences of alcohol relapse prevention medication, views of a telephone behavioural modification intervention delivered by pharmacists and the use of Contingency Management (CM) to support acamprosate adherence following assisted alcohol withdrawal.
METHODS
Four focus groups were conducted within four alcohol treatment and recovery groups across England (UK), with service users with lived experience of alcohol dependence (26 participants). Semi-structured topic guide was used to explore participants' views and experiences of alcohol relapse prevention medication, a telephone behavioural modification medication intervention delivered by pharmacists, and the use of CM to support acamprosate adherence. These were audio-recorded, transcribed verbatim and thematically analysed inductively and deductively.
RESULTS
Four themes were identified: concerns about support and availability of alcohol relapse prevention medication; lack of knowledge and understanding about acamprosate treatment; positive perceptions of acamprosate adherence telephone support from pharmacists; and negative perceptions of CM to support acamprosate adherence. There were misunderstandings about acamprosate's mode of action and strong negative beliefs about CM. However, most were positive about pharmacists' new role to support acamprosate adherence.
CONCLUSION
This study highlighted challenges service users face to commence alcohol relapse prevention medication. It appears service users could benefit from a pharmacist-led telephone intervention to improve understanding about acamprosate medication, particularly, if delivered in an engaging and motivating way.
Topics: Acamprosate; Alcoholism; Attitude of Health Personnel; Community Pharmacy Services; Humans; Medication Adherence; Pharmacists; Professional Role; Secondary Prevention; Substance Withdrawal Syndrome
PubMed: 35292814
DOI: 10.1093/alcalc/agac011 -
American Journal of Therapeutics 2020
Topics: Acamprosate; Catatonia; Humans
PubMed: 31356347
DOI: 10.1097/MJT.0000000000000991