Medications for Alcohol Use Disorder.

Excessive alcohol use is a leading cause of preventable death in the United States, with alcohol-related deaths increasing during the pandemic. The Substance Abuse and Mental Health Services Administration recommends that physicians offer pharmacotherapy with behavioral interventions for patients diagnosed with alcohol use disorder. Several medications are available to help patients reduce drinking and maintain abstinence; however, in 2019, only 7.3% of Americans with alcohol use disorder received any treatment, and only 1.6% were prescribed medications to treat the disorder. Strong evidence shows that naltrexone and gabapentin reduce heavy-drinking days and that acamprosate prevents return-to-use in patients who are currently abstinent; moderate evidence supports the use of topiramate in decreasing heavy-drinking days. Disulfiram has been commonly prescribed, but little evidence supports its effectiveness outside of supervised settings. Other medications, including varenicline and baclofen, may be beneficial in reducing heavy alcohol use. Antidepressants do not decrease alcohol use in patients who do not have mood disorders, but they may help patients who meet criteria for depression to decrease their alcohol intake. Systematic policies are needed to expand the use of medications when treating alcohol use disorder in inpatient and outpatient populations.

Pharmacological interventions for alcohol misuse in correctional settings: A systematic review.

BACKGROUND: The prevalence of alcohol use disorder (AUD) is estimated to be 10 times higher amongst individuals in the criminal justice system than the general population. Alcohol use is also one of the strongest modifiable risk factors for recidivism. One intervention that has been shown to be effective in reducing alcohol consumption in the general population is medication-assisted treatment (MAT), and this systematic review synthesized the existing evidence on MAT for AUD in correctional settings. METHODS: Empirical, peer-reviewed studies on approved medications for AUD in correctional populations were searched in major databases. One hundred sixty-two articles were initially screened and 14 eligible articles were included in the final review. Four articles examined disulfiram, and 10 articles examined naltrexone. RESULTS: The studies on disulfiram were considerably older than those on naltrexone, predating contemporary scientific standards. Disulfiram in combination with substantial contingencies in a supervised setting significantly reduced alcohol-related measures of consumption and recidivism and had acceptable safety and tolerability. All naltrexone studies showed significant reductions in alcohol-related measures, but effects on recidivism were mixed. The naltrexone studies indicated that it was highly acceptable and well tolerated. In addition, offenders receiving naltrexone had significantly greater medication adherence, treatment attendance, and treatment duration than with placebo. CONCLUSIONS: A small number of studies on pharmacological interventions for AUD in the correctional population suggest that MAT is effective in reducing alcohol consumption, although results on recidivism are mixed. On balance, the evidence was more supportive of naltrexone in reducing alcohol-related outcomes than disulfiram and it may also be a more feasible intervention in correctional settings. Further research on MAT to address AUD in correctional populations with larger sample sizes, longer duration, and in combination with behavioral interventions is warranted.

Effectiveness of Psychoanalytic-Interactional Group Therapy vs. Behavioral Group Therapy in Routine Outpatient Treatment of Alcohol-Dependent Patients.

BACKGROUND: The cognitive behavioral therapy has been extensively investigated to assess relapse prevention rates in patients with alcohol dependence. In contrast, only little is known regarding the effectiveness of psychoanalytical psychotherapy in relapse prevention, although this treatment is widely used and especially so in Germany. The aim of this quasi-randomized study was to compare the effectiveness of these two group treatments' approaches under the condition of routine outpatient treatment in a non-university hospital. METHODS: After inpatient detoxification, patients with alcohol dependence were allocated either to combined behavioral intervention (CBI) or to psychoanalytic-interactional therapy (PIT). The group treatment was carried out weekly over a period of six months. Also, the clinical care package included both individual treatment sessions (e.g. every 4-6 weeks) and abstinence supporting medication. The main outcome criteria included retention rates and frequency of alcohol relapse. RESULTS: Some 215 patients (mean age 49.6 years [standard deviation, 10], 56.7% males, with a mean duration of alcohol dependence of 16.5 years [range: 1-50 years]) were included in the study. Overall, CBI clients showed a retention rate of 66.7%, compared to 81.8% for PIT clients (p =.008). An intention-to-treat analysis of alcohol relapses showed a significant difference between PIT and CBI groups (PIT: 33.6%; CBI: 49.5%; p =.018). There were no statistically significant differences between the 2 groups in terms of prescription rates of disulfiram, naltrexone or acamprosate. CONCLUSIONS: Notwithstanding the study limitations, PIT seemed here to be at least as effective as CBI in terms of retention and relapse prevention rates' levels.

Efficacy of Medications Approved for the Treatment of Alcohol Dependence and Alcohol Withdrawal Syndrome in Female Patients: A Descriptive Review.

The aim of this study was to evaluate whether the number of women recruited for studies to establish the efficacy of medications approved for treatment of alcohol dependence (AD) and of alcohol withdrawal syndrome (AWS) is sufficient to reveal possible gender differences in the response to these medications and in suggesting the use of different doses in female patients. Our results show that the rates of women recruited for studies evaluating the efficacy of disulfiram (1%), benzodiazepines (3%), and anticonvulsants (13%) were too low to establish possible gender differences. The rates of women recruited for studies evaluating the efficacy of acamprosate (22%), naltrexone (23%), and nalmefene (30%) were higher and allowed evaluation of data obtained for female patients. Women receive medications for treatment of AD and/or AWS for which efficacy has been demonstrated in studies in which men were more largely represented.

Medications for the Treatment of Alcohol Dependence-Current State of Knowledge and Future Perspectives from a Public Health Perspective.

No single effective therapy for alcohol abuse has been found, despite it being a serious sociological and economic problem for hundreds of years. It seems difficult to find a single drug as a panacea for the alcohol problem due to the complexity of the pathophysiology of alcohol dependence. The purpose of this narrative review is to review existing and potentially future pharmaceuticals for the treatment of alcohol dependence in the most affordable way possible. Psychotherapy is the mainstay of treatment for alcoholism, while few drugs approved by legislators are available in the augmentation of this treatment, such as acamprosate, disulfiram, and naltrexone, approved by the FDA, and nalmefene by the EMA. There are recent reports in the literature on the possibility of using baclofen, topiramate, varenicline, and gabapentin in the treatment of alcohol dependence. Moreover, the results of recent clinical trials using psychoactive substances such as psilocybin and MDMA appear to be a breakthrough in the modern treatment of alcohol abuse. Despite this initial optimism, a lot of scientific effort is still needed before new pharmacological methods supporting the treatment of alcohol dependence syndrome will be widely available.

Low rates of prescribing alcohol relapse prevention medicines in Australian Aboriginal Community Controlled Health Services.

INTRODUCTION: Alcohol dependence is a chronic condition impacting millions of individuals worldwide. Safe and effective medicines to reduce relapse can be prescribed by general practitioners but are underutilised in the general Australian population. Prescription rates of these medicines to Aboriginal and Torres Strait Islander (First Nations) Australians in primary care are unknown. We assess these medicines in Aboriginal Community Controlled Health Services and identify factors associated with prescription. METHODS: Baseline data (spanning 12 months) were used from a cluster randomised trial involving 22 Aboriginal Community Controlled Health Services. We describe the proportion of First Nations patients aged 15+ who were prescribed a relapse prevention medicine: naltrexone, acamprosate or disulfiram. We explore associations between receiving a prescription, a patient AUDIT-C score and demographics (gender, age, service remoteness) using logistic regression. RESULTS: During the 12-month period, 52,678 patients attended the 22 services. Prescriptions were issued for 118 (0.2%) patients (acamprosate n = 62; naltrexone n = 58; disulfiram n = 2; combinations n = 4). Of the total patients, 1.6% were 'likely dependent' (AUDIT-C ≥ 9), of whom only 3.4% received prescriptions for these medicines. In contrast, 60.2% of those who received a prescription had no AUDIT-C score. In multivariate analysis, receiving a script (OR = 3.29, 95% CI 2.25-4.77) was predicted by AUDIT-C screening, male gender (OR = 2.24, 95% CI 1.55-3.29), middle age (35-54 years; OR = 14.41, 95% CI 5.99-47.31) and urban service (OR = 2.87, 95% CI 1.61-5.60). DISCUSSION AND CONCLUSIONS: Work is needed to increase the prescription of relapse prevention medicines when dependence is detected. Potential barriers to prescription and appropriate ways to overcome these need to be identified.

Psychosis induced by the interaction between disulfiram and methylphenidate may be dose dependent.

There are few studies describing psychiatric symptoms occurring when methylphenidate and disulfiram are used together. The authors report a case of disulfiram and methylphenidate interaction in which psychotic symptoms could be dose dependent. The patient, diagnosed of alcohol and cocaine dependence and attention deficit hyperactivity disorder (ADHD), started treatment with methylphenidate increasing doses and disulfiram 250 mg/day over 4 weeks. During the first 2 weeks at doses of 36 mg/day of methylphenidate and maintaining disulfiram, side effects were not observed. However, by increasing to 54 mg/day, psychotic symptoms were detected. The authors reported that the effects are dose dependent. This is the first report about dose-dependent side effects in substance use disorder with ADHD.

[The patient with an alcohol abuse problem family doctor practice]. / Pacjent z problemem alkoholowym w praktyce lekarza rodzinnego.

Doctors of many specialties, including the family doctors, encounter the problems of alcohol abuse in their patients. Due to the fact that many symptoms of dangerous diseases can be masked by the fact of alcoholism, a brief doctor's visit has to be conducted with watchfulness, caution and care. Family doctors have some brief testes (such as CAGE test, AUDIT test), besides of precise anamnesis and blood chemistry, which make it easier to identify a patient with an alcohol problem. People with disabilities are more exposed to alcohol abuse since they often experience additional factors such as unemployment, social isolation and homelessness. All of the above factors foster the more frequent alcohol usage. In Poland the main treatment method of alcohol addiction is psychotherapy practiced in the rehab centers. The detoxification treatment is voluntary and free of charge even though the patients checking into those facilities are doing it against their will. They are forced to do so by entourage, family, spouse or risk of unemployment. Acamprozate is considered as a drug, run to extend abstaining from alcohol. In the past, therapy with disulfiram substance was common, but now, it is considered as unethical behaviour. In practice of medicine, a patient with alcohol addiction creates not onlya medical but also legal problems. Therefore keeping of detailed medical documentation is very important as it may become significant evidence in the future.

Advantages and disadvantages of disulfiram coadministered with popular addictive substances.

Disulfiram (DSF) is a well-known anti-alcohol agent that inhibits aldehyde dehydrogenase and results in extreme 'hangover' symptoms when consumed with alcohol. This drug, however, has been suggested as useful in other forms of drug addiction due to its beneficial potential in both drug abuse reduction and withdrawal. However, among other drugs used in alcohol dependence, it carries the greatest risk of pharmacological interactions. Concomitant use of DSF and central nervous system stimulants usually leads to harmful, undesirable effects. To date, there is still limited data regarding the detailed safety profile of DSF as a concomitant drug. In this review article, we outline the current state of knowledge about DSF, its broad pharmacological action, as well as therapeutic effects, with a particular emphasis on the molecular understanding of its potential pharmacodynamic interactions with common addictive substances (e.g., alcohol, cocaine, cannabinoids, opioids) supported by relevant examples.

An open randomized trial comparing disulfiram and topiramate in the treatment of alcohol dependence.

This study compared the efficacy of disulfiram (DSF) and topiramate (TPM) for preventing alcoholic relapse in an open study of routine clinical practice in India. One hundred alcohol-dependent men with family members who agreed to encourage medical compliance and to accompany them for follow-up were randomly allocated to 9 months of treatment with DSF or TPM. Weekly psychotherapy was also provided. There was no blinding of conditions for the psychiatrist, patient, or family members. Supervision and support of the family member were used in the maintenance of compliance among the patients. Alcohol consumption, craving, and adverse events were recorded weekly for 3 months and then biweekly. Serum gamma glutamyl transferase was measured at the start and at the end of the study. At the end of the trial, 92 patients were still in contact. Relapse occurred at a mean of 133 days for DSF as compared with 79 days for TPM. At 9 months, 90% of DSF patients, as compared with 56% of TPM patients, remained abstinent. TPM-treated patients did show less craving than DSF patients did. Further comparisons between these drugs in different treatment settings and patient populations are warranted.

Acute pneumonitis associated with nickel carbonyl exposure in the workplace.

BACKGROUND: We describe the clinical course of one industrial technician occupationally exposed to nickel carbonyl (NiC). CASE REPORT: A 50-year-old male industrial technician presented with complaints of nausea, myalgia, and cough to a local clinic after suspected occupational exposure to nickel carbonyl. He has no history of lung disease or smoking. His initial urine nickel concentration was 692 ug/L. He had infiltrates on the initial chest X-ray (CXR) and an oxygen saturation (O2) of 97% on room air. The patient was started on disulfiram 1 g by mouth (PO), 500 mg six hours after the first dose, then 250 mg twice daily for five days with prednisone 60 mg by mouth for five days. He presented 48 hours later with worsening respiratory symptoms. His O2 saturation decreased to 85% despite two days of oral steroids, and he was admitted to a hospital. He received prednisone 60 mg/day PO, 4 L nasal O2, and disulfiram 500 mg twice daily. He was discharged on day 7 post-exposure with disulfiram and prednisone. Case discussions: NiC is a severe respiratory irritant. Disulfiram was used off-label and was based on an established company protocol. CONCLUSIONS: Inhalation exposure to NiC resulted in a delayed respiratory dysfunction which responded to disulfiram treatment.

Treatment of schizophrenia and comorbid substance abuse: pharmacologic approaches.

Co-occurring substance use disorder is common among patients with schizophrenia, and its presence greatly worsens the course of schizophrenia. A number of theories have been introduced to explain the increased rate of substance use disorder in these patients. These theories include the notion that substance use could trigger psychotic symptoms in vulnerable individuals and the idea that the substances are used to self-medicate symptoms of schizophrenia. Our group and others have advanced a neurobiological hypothesis to explain this comorbidity-that a mesocorticolimbic brain reward circuit underlies the substance use disorder in patients with schizophrenia. Treatment of substance use disorder in these patients is best done with integrated treatment programs that combine psychosocial interventions with pharmacotherapy. Recent data suggest that the atypical antipsychotic clozapine and perhaps other atypical agents may lessen substance use in patients with schizophrenia. My colleagues and I have proposed that clozapine's effect in these patients may be related to its ability to decrease the brain reward circuit dysfunction. Research is continuing on the use of atypical antipsychotics in patients with schizophrenia and comorbid substance abuse. The adjunctive use of naltrexone or other agents also may be helpful. Further research on the optimal pharmacologic approach to patients with dual diagnosis is needed.

Psychotic spectrum disorders and alcohol abuse: a review of pharmacotherapeutic strategies and a report on the effectiveness of naltrexone and disulfiram.

The rate of substance-use disorders in patients with mental illnesses within the psychotic spectrum, such as schizophrenia, schizoaffective disorder, and bipolar disorder, is higher than the rate observed in the general population and is associated with significant morbidity and mortality. Although there are currently 3 medications approved by the Food and Drug Administration for the treatment of alcohol dependence, no medications have been approved for the specific treatment of dually diagnosed patients. A small but growing body of literature supports the use of 2 of these medications, disulfiram and naltrexone, in dually diagnosed individuals. This article outlines a review of the literature about the use of disulfiram and naltrexone for alcoholism and in patients with comorbid mental illness. In addition, results are presented of a 12-week randomized clinical trial of disulfiram and naltrexone alone and in combination for individuals with Axis I disorders and alcohol dependence who were also receiving intensive psychosocial treatment. Individuals with a psychotic spectrum disorder, including schizophrenia, schizoaffective disorder, and bipolar disorder, had worse alcohol outcomes than those without a psychotic spectrum disorder. Individuals with a psychotic spectrum disorder had better alcohol-use outcomes on an active medication compared with placebo, but there was no clear advantage of disulfiram or naltrexone or of the combination. Retention rates and medication compliance in the study were high and exceeded 80%. Pharmacotherapeutic strategies should take into account the advantages and disadvantages of each medication. Future directions of pharmacotherapeutic options are also discussed.

The BRENDA model: integrating psychosocial treatment and pharmacotherapy for the treatment of alcohol use disorders.

While the U.S. Food and Drug Administration has approved several medications for the treatment of alcohol-related problems, their use has not gained wide acceptance in the United States. Typically, patients with alcohol use disorders are only referred to psychosocial support (e.g., Alcoholics Anonymous). However, the use of pharmacotherapy may complement psychosocial treatments, as evidence shows that pharmacotherapy can improve treatment outcomes. The effectiveness of pharmacotherapy depends on patient compliance with taking the medication and the context in which the medication is administered. BRENDA is a psychosocial program designed specifically to be used by many types of healthcare providers, including primary care clinicians. Designed to enhance medication and treatment compliance, BRENDA is an ideal approach for use in conjunction with pharmacotherapy. The BRENDA approach has 6 components: 1) a biopsychosocial evaluation; 2) a report of findings from the evaluation given to the patient; 3) empathy; 4) addressing patient needs; 5) providing direct advice; and 6) assessing patient reaction to advice and adjusting the treatment plan as needed. This paper describes these components and discusses how the empirical support for each component is linked to the enhancement of medication compliance and the improvement of treatment outcomes.

Disulfiram inhibition of cyanide formation after acetonitrile poisoning.

CONTEXT: Cyanide poisoning may be caused by acetonitrile, a common industrial organic solvent and laboratory agent. OBJECTIVE: To describe the potential use of disulfiram in treating acetonitrile poisoning in a human clinical case and to further study its effect in human liver microsomes in vitro. CASE DETAILS: A 30-year-old man initially presented with a cholinergic toxic syndrome following ingestion of aldicarb. Toxicological analysis revealed coingestion of ethanol. He subsequently developed severe metabolic acidosis caused by the cyanogenic compound acetonitrile which was erroneously interpreted as acetone in the chromatogram. After three treatments with hydroxocobalamin (5 g i.v.) and sodium thiosulfate (12.5 g i.v.) on days 2, 3, and 5, he had transient improvement but recurrent lactic acidosis. Treatment with disulfiram was associated on day 7 with resolution of metabolic acidosis and slowing of the decrease in acetonitrile concentration. He recovered from acetonitrile toxicity completely. The time course of acetonitrile, thiocyanate, and cyanide concentrations suggested that disulfiram inhibited cyanide formation. RESULTS: In vitro experiments with human liver microsomes showed the cyanide concentration was significantly lower after incubation with acetonitrile and disulfiram than acetonitrile alone (a mean 60% reduction in cyanide level). DISCUSSION: Although disulfiram was given late in the course of the poisoning it is possible that it contributed to the recovery.

Disulfiram for binge eating disorder: an open trail.

OBJECTIVE: To evaluate the efficacy and safety of disulfiram for treatment of binge eating disorder. METHOD: Two hundred and fifty milligrams per day of disulfiram was administered to 12 patients affected by binge eating disorder for 16 weeks; the number of binge eating episodes per week and the number of participants who reported side effects were evaluated. RESULTS: Nine participants (75.0%) completed the trial, while the other 3 (25.0%) discontinued prematurely. Disulfiram significantly decreased the mean frequency of binge eating episodes per week from 7.9±1.2 to 0.9±0.6 (p<.001). All patients (100.0%) reduced the frequency of binge eating episodes, and 7 participants (58.3%) achieved remission of binge eating. Eleven participants (91.7%) reported side effects [drowsiness (N=9), headache (N=7), dysgeusia (N=3), tachycardia (N=3), dizziness (N=2), and nausea (N=2)]. DISCUSSION: While disulfiram reduced the frequency of binge eating episodes, side effects were observed in the majority of participants. Longer-term placebo-controlled studies are warranted to exclude the contribution of a placebo response from these results and to evaluate drugs with similar pharmacological activity but improved tolerability.

Increased sympathetic nervous system activity in alcoholic patients treated with disulfiram.

The authors measured plasma levels of norepinephrine (NE) and dopamine beta-hydroxylase (DBH), pulse rates, and blood pressures of 81 hospitalized alcoholic patients. Treatment with 500 mg/day of disulfiram (but not 250 mg/day or placebo) resulted in small but significant increases in plasma NE and in blood pressure. The 500-mg dose did not appreciably inhibit DBH. Patients receiving high doses of disulfiram should have their blood pressure monitored and their dose decreased to 250 mg/day when possible.

Disulfiram treatment of alcoholism.

PURPOSE: For 40 years, disulfiram has been the alcohol-aversive drug used most frequently by American physicians in the treatment of alcohol dependency disorders. We reviewed the clinical literature regarding the risks, benefits, indications, and efficacy of this controversial drug and summarized current knowledge of this therapy. CONCLUSIONS: Disulfiram will produce an aversive reaction with ethanol, usually at a dose between 250 mg/day and 500 mg/day, although some patients may not have an aversive reaction at this level. Cardiac, hepatic, and neurologic toxicity can also occur within this dosage range. If disulfiram is to be used, the patient must clearly understand the risks of drinking while taking the drug, and the physician and patient must agree about the need for continued clinical supervision and monitoring for efficacy and side effects. The physician must also recognize that disulfiram is only an adjunctive therapy and that continued support, supervision, and other therapeutic measures are required. Disulfiram is probably effective in reducing the frequency of alcohol consumption in the compliant patient over the short term (e.g., 6 months). Certain subgroups of patients, such as those who are older, those who are more socially stable, and those who are well-motivated, may experience a beneficial effect for longer periods. The drug may be most effective in reducing short-term alcohol consumption when the compliance of the patient is supervised, although consideration of this kind of therapy includes the practical problems of supervising the patient and concerns that the supervising person may be placed in a difficult position. Prescription of disulfiram without accompanying education, counseling, and concomitant alcoholism therapy is not beneficial. Disulfiram has no proven effect on the long-term outcome of alcoholism.