Assessing the efficacy of medical treatments for alcohol use disorders

Alcohol use disorders (AUDs) are common health problems that have a significant impact on society as a whole. There is a need for more effective treatments. In the last two decades, evidence for the efficacy of pharmacological approaches to treatment has increased. Although it has long been clear that medications are needed for the treatment of the alcohol withdrawal syndrome, the important role of medications in the longer-term treatment of AUDs has only recently been appreciated. In particular, naltrexone, acamprosate and topiramate appear to be efficacious treatments, especially when combined with psychosocial interventions that emphasise compliance with medication and encourage treatment retention. The goal of this review is to bring together the existing literature supporting the usefulness of pharmacological treatments for the alcohol withdrawal syndrome, for longer-term treatment of AUDs, and for comorbid AUDs and other psychiatric disorders. In addition, opportunities for future research will be identified.     

Treatment for comorbid borderline personality disorder and alcohol use disorders: A review of the evidence and future recommendations

There is a high degree of comorbidity between borderline personality disorder (BPD) and alcohol use disorders (AUDs). There is some evidence that this pattern of comorbidity may be associated with poorer prognosis. Although there are many different psychotherapeutic and pharmacological treatments for BPD and AUDs when they occur alone, there are very few treatment options when they occur together. The objective of this article was to review the existing treatment options-both psychotherapeutic and pharmacological-for patients with dual diagnoses of BPD and AUDs and to explore alternative treatment options that warrant further study. There have been a number of studies that have examined the efficacy of specific psychotherapies targeting drinking among patients with comorbid BPD; however, their efficacy in reducing BPD symptoms is unknown. There are also three psychotherapies that were specifically developed for patients with BPD and substance use disorders (SUDs), but only one of these (Dynamic Deconstructive Psychotherapy) has been tested among patients with dual diagnoses of BPD and AUDs. Research on pharmacotherapy for dual diagnoses of BPD and AUD is scarce, and no study has yet explored medication options that can concurrently manage symptoms of BPD and decrease alcohol consumption. Interestingly, there is growing evidence that anticonvulsants and second generation antipsychotics, the recent medications of choice for the management of BPD symptoms, may also reduce alcohol craving and consumption. Although premature, these findings are encouraging especially for this population of patients for whom treatment options are very limited. (PsycINFO Database Record (c) 2012 APA, all rights reserved).     

The use of divalproex in the treatment of addictive disorders

To date, few medications have shown efficacy in the treatment of addictive disorders. The lack of effective treatments has led to the evaluation of a variety of pharmacotherapies to reduce alcohol or illicit drug use. The anticonvulsant agents are a class of medications that may represent novel treatments for addictive disorders. One of the most studied anticonvulsant agents in the treatment of addictive disorders has been valproate. This article will review the literature regarding the use of valproate in treating alcohol withdrawal symptoms and in reducing the use of alcohol and cocaine.     

Adefovir dipivoxil in chronic hepatitis B: history and current uses

Introduction: Sodium oxybate (SMO) has been shown to be safe and effective in the treatment of patients with alcohol use disorders (AUDs); it was approved in Italy and Austria for the treatment of alcohol withdrawal syndrome and for relapse prevention. The focus of this review is to discuss the clinical evidence on the therapeutic potential of SMO for AUDs.

Areas covered: This review covers the studies in patients with alcohol withdrawal syndrome who received SMO for the treatment of withdrawal symptoms and the studies in patients with AUDs who received SMO to achieve total alcohol abstinence, reduction of alcohol intake, and relapse prevention. Relevant medical literature on SMO was identified by searching databases including MEDLINE and EMBASE (searches last updated 20 September 2013), bibliographies from published literature, clinical trial registries/databases, and websites.

Expert opinion: SMO has proved safe and effective in the treatment of alcohol withdrawal syndrome and in the prevention of relapses. Craving for and abuse of SMO have been reported, in particular in some subtypes of alcoholic patients, e.g., those affected by co-addiction and/or psychiatric comorbidity. Future multicenter, multinational, randomized clinical trials should be useful to optimize the treatments in relation with patients' characteristics, for example, pharmacogenetic, neurobiological, and psychological.     

Pharmacotherapy of alcoholism – an update on approved and off-label medications

Introduction: Only a few medications are available for the treatment of alcohol use disorders (AUDs).

Areas covered: This paper discusses approved AUD medications, including the opioid antagonists naltrexone and nalmefene (the latter is licensed for reduction of alcohol consumption only), the putative glutamate receptor antagonist acamprosate and the aldehyde dehydrogenase inhibitor disulfiram. It also covers off-label medications of interest, including topiramate, gabapentin, ondansetron, varenicline, baclofen, sodium oxybate and antidepressants. Clinical implications, benefits and risks of treatment are discussed.

Expert opinion: Acamprosate, naltrexone, nalmefene and disulfiram are the only approved ‘alcohol-specific’ drugs. Acamprosate and naltrexone have been evaluated in numerous clinical trials and represent evidence-based treatments in AUDs. Nalmefene use, however, is controversial. Supervised disulfiram is a second-line treatment approach. Compounds developed and licensed for different neuropsychiatric disorders are potential alternatives. Encouraging results have been reported for topiramate, gabapentin and also varenicline, which might be useful in patients with comorbid nicotine dependence. The GABA (γ-aminobutyric acid)-B receptor agonist baclofen has shown mixed results; it is currently licensed for the treatment of AUDs in France only. Gabapentin may be close to approval in the USA. Further studies of these novel treatment approaches in AUDs are needed.     

Anticonvulsant drugs in the treatment of substance withdrawal

Although detoxification cannot, in itself, be considered a treatment for addiction, it is one of the most pivotal phases. In order to facilitate entry into recovery and/or rehabilitation programs, a detoxification treatment has to be experienced as easy and safe by the patient. In consideration of the many inconveniences related to standard withdrawal treatments, there is an interest in developing alternative pharmacological strategies. The main rationales for using anticonvulsants in substance-abuse patients are their lack of addiction potential, evidence support a role of kindling mechanisms in withdrawal syndromes and their efficacy in comorbid psychiatric disorders. The available data currently support the utilization of carbamazepine as a treatment for detoxification from benzodiazepines, alcohol and opiates, and as a useful agent to reduce cocaine consumption. The use of valproate is well corroborated for alcohol detoxification and it seems to be a promising treatment for the reduction of cocaine use; however, it has been found to be ineffective against benzodiazepine withdrawal symptoms. Some preliminary data suggest that lamotrigine could be useful in opiate and cocaine dependence. Gabapentin shows potential as a treatment for cocaine dependence, and some case reports have stimulated interest in this agent for alcohol and benzodiazepine detoxification. Due to its particular pharmacological profile, topiramate is one of the most interesting newer anticonvulsants. It has been found to be efficacious in opiate and possibly benzodiazepine detoxification and also has theoretical potential as a preventive therapy.     

Clinical issues related to the costs of alcoholism

Alcohol (ethanol) use disorders are prevalent in many countries and are associated with significant social and health costs. Little is known, however, about the comparative cost effectiveness of treatments for alcoholism. Pharmacoeconomic evaluations are largely (if not wholly) absent from the alcoholism treatment outcome database. We discuss pharmacological approaches to the treatment of alcohol withdrawal and dependence, describing agents that ameliorate withdrawal symptoms, deter alcohol consumption, reduce alcohol craving and produce conditioned alcohol aversion. Cost-relevant clinical considerations are elucidated and recommendations for cost-conscious pharmacological treatment of alcohol dependence are proffered.     

An overview of the development of medications including novel anticonvulsants for the treatment of alcohol dependence

The development of treatments for alcohol dependence has been significantly complicated by the multiple actions of ethanol at the neurotransmitter level, heterogeneity among patients with alcohol dependence, the complexity of defining and measuring the phenomenon of craving, and the challenge of quantifying alcohol intake in patients. Increasingly, anticonvulsant medications are showing promise for the safe and effective amelioration of alcohol withdrawal symptoms. Furthermore, there is evidence that anticonvulsant medications are promising treatments for reducing drinking and preventing relapse among alcohol-dependent individuals. In recent years, many medications have been evaluated for the treatment of alcohol dependence, including those that interact with dopaminergic, serotonergic, opioid or glutamate and/or GABA systems. So far, naltrexone, acamprosate and, more recently, the anticonvulsant, topiramate, have shown some efficacy for the treatment of heterogeneous populations of individuals with alcohol dependence. Both ondansetron and sertraline appear to have some efficacy in treating different subgroups of alcoholic.     

An overview of the development of medications including novel anticonvulsants for the treatment of alcohol dependence

The development of treatments for alcohol dependence has been significantly complicated by the multiple actions of ethanol at the neurotransmitter level, heterogeneity among patients with alcohol dependence, the complexity of defining and measuring the phenomenon of craving, and the challenge of quantifying alcohol intake in patients. Increasingly, anticonvulsant medications are showing promise for the safe and effective amelioration of alcohol withdrawal symptoms. Furthermore, there is evidence that anticonvulsant medications are promising treatments for reducing drinking and preventing relapse among alcohol-dependent individuals. In recent years, many medications have been evaluated for the treatment of alcohol dependence, including those that interact with dopaminergic, serotonergic, opioid or glutamate and/or GABA systems. So far, naltrexone, acamprosate and, more recently, the anticonvulsant, topiramate, have shown some efficacy for the treatment of heterogeneous populations of individuals with alcohol dependence. Both ondansetron and sertraline appear to have some efficacy in treating different subgroups of alcoholic.     

An overview of medications for the treatment of alcohol withdrawal and alcohol dependence with an emphasis on the use of older and newer anticonvulsants

There is a growing interest in the development of new pharmacological tools for treating alcohol withdrawal and dependence. A number of anticonvulsants including valproate and carbamazepine have been shown to be safe and effective alternatives to benzodiazepines for treating alcohol withdrawal. These agents are relatively safe, are free from demonstrated abuse liability, and do not usually potentiate the psychomotor and cognitive effects of alcohol. For the treatment of alcohol dependence, there is a growing literature on the utility of medications that have neurochemical effects at opioid, serotonergic, GABAergic, and glutamate receptors. Furthermore, as a class of medication, there appears to be a growing interest in investigating the utility of novel anticonvulsants such as topiramate for the treatment of alcohol dependence.     

The growth of treatment research in alcohol and drug use disorders: a computerized literature search

Index Medicus was searched to compare the number of articles on treatment trials for alcohol and for non-alcohol drug use disorders (abuse, dependence, withdrawal, intoxication, etc.) to that of two control conditions--anxiety and obesity--for the period 1967-1988. Over the entire 22 years, the number of articles for alcohol use disorders increased an average of 2.7 articles every 2 years and 5.8/2 years for drug use disorders compared to 5.7/2 years for obesity and 5.8/2 years for anxiety disorders. Over the most recent 8 years, articles for alcohol use disorders increased 7.7/2 years and for drug use disorders 7.9/2 years compared to--2.9/2 years and 12.0/2 years for obesity and anxiety disorders. The proportion of articles that cited using only pharmacotherapy decreased over time; however, studies of alcohol and drug withdrawal continue to almost exclusively use pharmacological therapies. We conclude that treatment research in alcohol and drug use disorders is growing as rapidly as that in similar psychological and psychiatric conditions and that such growth is not due to a focus on pharmacological treatments.     

Novel pharmacological approaches for treating tobacco dependence and withdrawal: current status

Increasing the diversity and availability of medications for the treatment of tobacco dependence and/or withdrawal, to aid in the achievement of smoking cessation, is crucial to meet the diverse needs of tobacco users. Despite a general awareness that smoking is harmful and widespread interest in smoking cessation, nearly 50 million adults in the US and 1.3 billion worldwide continue to smoke. Nicotine replacement therapies are effective in the treatment of tobacco dependence and withdrawal, but do not meet the needs of all tobacco users. Improvement of tobacco dependence and/or withdrawal treatments is likely to rely on novel pharmacological approaches that include new chemical entities and new formulations of current drugs. In addition, new indications for treating tobacco dependence and withdrawal show promise for reducing tobacco use and associated disease. This article focuses on a range of novel pharmacological approaches for the treatment of tobacco dependence and/or withdrawal, including oral and pulmonary nicotine delivery and the following non-nicotinic medications: antidepressants, an alpha4beta2 nicotine partial agonist, an alpha2-noradrenergic agonist, cytochrome P450 (CYP) 2A6 inhibitors, opioid antagonists and GABAergic medications. In addition to existing medications, this article addresses novel medications in the clinical development stage and those that have been evaluated previously. Novel medications in the clinical development stage include at least three nicotine vaccines and the cannabinoid receptor acting drug rimonabant. Medications evaluated previously include lobeline, mecamylamine and an anticholinergic drug regimen comprising atropine, scopolamine and chlorpromazine. Having not been approved by major drug regulatory authorities for the treatment of tobacco dependence and/or withdrawal, these medications have been evaluated in an experimental capacity.     

Improving the Quality of Substance Dependency Treatment with Pharmacotherapy

This article provides an overview of current pharmacological treatments for alcohol, opioid, cocaine, and nicotine use disorders. Guidelines for a “patient-treatment” matching framework to physicians working with various “substance-abusing” patients are presented, as well as recommendations regarding when to initiate and discontinue pharmacotherapy. Standard and newer pharmacological treatments for substance dependence are reviewed, as well as therapies that may be especially useful when treating the patient with comorbid substance dependency and psychiatric disorders. To maximize the therapeutic benefits of substance dependency treatment, patients should be individually assessed and provided adjunctive medications as clinically indicated. Specific areas for future laboratory and/or clinical research are recommended.     

Improving the quality of substance dependency treatment with pharmacotherapy

This article provides an overview of current pharmacological treatments for alcohol, opioid, cocaine, and nicotine use disorders. Guidelines for a "patient-treatment" matching framework to physicians working with various "substance-abusing" patients are presented, as well as recommendations regarding when to initiate and discontinue pharmacotherapy. Standard and newer pharmacological treatments for substance dependence are reviewed, as well as therapies that may be especially useful when treating the patient with comorbid substance dependency and psychiatric disorders. To maximize the therapeutic benefits of substance dependency treatment, patients should be individually assessed and provided adjunctive medications as clinically indicated. Specific areas for future laboratory and/or clinical research are recommended.     

Alcohol use disorders and current pharmacological therapies: the role of GABAA receptors

Alcohol use disorders (AUD) are defined as alcohol abuse and alcohol dependence, which create large problems both for society and for the drinkers themselves. To date, no therapeutic can effectively solve these problems. Understanding the underlying mechanisms leading to AUD is critically important for developing effective and safe pharmacological therapies. Benzodiazepines (BZs) are used to reduce the symptoms of alcohol withdrawal syndrome. However, frequent use of BZs causes cross-tolerance, dependence, and cross-addiction to alcohol. The FDA-approved naltrexone and acamprosate have shown mixed results in clinical trials. Naltrexone is effective to treat alcohol dependence (decreased length and frequency of drinking bouts), but its severe side effects, including withdrawal symptoms, are difficult to overcome. Acamprosate showed efficacy for treating alcohol dependence in European trials, but two large US trials have failed to confirm the efficacy. Another FDA-approved medication, disulfiram, does not diminish craving, and it causes a peripheral neuropathy. Kudzu is the only natural medication mentioned by the National Institute on Alcohol Abuse and Alcoholism, but its mechanisms of action are not yet established. It has been recently shown that dihydromyricetin, a flavonoid purified from Hovenia, has unique effects on GABA_A receptors and blocks ethanol intoxication and withdrawal in alcoholic animal models. In this article, we review the role of GABA_A receptors in the treatment of AUD and currently available and potentially novel pharmacological agents.     

Cocaine misuse treatment in England

Three methods were used to identify the treatments given to cocaine misusers in England, and to make a preliminary assessment of effectiveness. First, a postal survey of all known drug misuse treatment services ascertained approximate numbers of cocaine misusers presenting and receiving a specified range of treatments. Secondly, staff at selected services were interviewed regarding treatment policies, and asked to subjectively rate short-term and long-term effectiveness. Thirdly, a cohort of individuals in treatment were studied prospectively to assess changes in drug usage and associated problems. Fifty percent of services responded to the survey, but there was known to be significant duplication in service listings and it is considered that a representative pattern of clinical activity has been detected. Approximately half those services had recently treated cocaine misusers, mainly using counselling, residential rehabilitation, and pharmacological treatments, in which 32 different medications were identified. Acupuncture was prominent in a minority of services. Staff interviews suggested several principles in managing cocaine misusers, while all treatments were rated as being more effective in short-term relief of withdrawal features than in enabling longer-term abstinence. The treatment cohort were mostly in residential rehabilitation, and marked reductions in drug use and related clinical and social problems were demonstrated.     

Treatment of alcohol withdrawal

Appropriate treatment of alcohol withdrawal (AW) can relieve the patient's discomfort, prevent the development of more serious symptoms, and forestall cumulative effects that might worsen future withdrawals. Hospital admission provides the safest setting for the treatment of AW, although many patients with mild to moderate symptoms can be treated successfully on an outpatient basis. Severe AW requires pharmacological intervention. Although a wide variety of medications have been used for this purpose, clinicians disagree on the optimum medications and prescribing schedules. The treatment of specific withdrawal complications such as delirium tremens and seizures presents special problems and requires further research.     

Alcohol use disorders in adolescents: epidemiology,diagnosis, psychosocial interventions,and pharmacological treatment

Alcohol (ethanol) abuse and dependence are the most common substance use disorders among adolescents. Binge drinking occurs in up to one-third of adolescents, and alcohol use disorders occur in about 6% of this age group. Adolescents with alcohol use disorders also typically have problems with other substances and comorbid mental disorders. Validated measures are available for the clinical detection and diagnosis of adolescent alcohol use disorders and related problems. Psychosocial interventions promoting abstinence are the most common treatments for alcohol use disorders, with empirical support particularly strong for family-based approaches. Pharmacological interventions may diminish the effects of alcohol withdrawal, prevent a return to alcohol consumption, or treat comorbid mental disorders. In this population, pharmacological interventions require further investigation and, where indicated, are generally considered to be supplementary to psychosocial approaches.     

Pharmacological treatment of attention-deficit/hyperactivity disorder in adults

With increased awareness that attention-deficit/hyperactivity disorder (ADHD) can persist beyond childhood, pharmacological treatment options for adults have expanded. Short-acting stimulants continue to be the first-line approach, demonstrating clinical efficacy and few adverse events in well-controlled trials, with long-acting stimulants also showing promise. Atomoxetine has also been reported to improve ADHD symptoms and associated dysfunction, although longer-term, head-to-head studies with stimulants are needed. Several antidepressants (e.g., desipramine and buproprion) appear to be effective in the treatment of adult ADHD, but to a lesser extent than stimulants. Data are limited in evaluating the impact of combining pharmacological treatments for ADHD and comorbid conditions. This paper describes the safety and efficacy of medications for treating the core symptoms, psychosocial features and cognitive dysfunctions associated with adult ADHD.     

Diagnosis, assessment, and treatment of alcohol withdrawal syndrome]

Alcohol withdrawal syndrome is the one of the most critical status among alcohol related disorders. Early detection, diagnosis, and appropriate treatment of alcohol withdrawal syndrome are keys to a successful outcome. This article describes the concrete method of diagnosis, assessment, and treatment of alcohol withdrawal syndrome.