Using naltrexone in inpatient alcoholism treatment

Naltrexone has been used successfully in outpatient settings as an adjunct to alcoholism treatment. This study examines the efficacy of using naltrexone in an inpatient treatment setting. Sixty-three alcohol-dependent patients who volunteered for a double-blind, placebo-controlled study were followed over the course of their 20 days in treatment and six months follow-up. A comparison group of 59 patients who did not volunteer were also studied over the same period of time. Patients in the study group were randomly assigned to receive naltrexone or placebo. Information was gathered daily on alcohol craving, drug craving and moods on self-reporting forms from the naltrexone and placebo groups, and from the comparison group. Follow-up data was gathered through self-report and through Washington State's TARGET management information system. No significant differences were found in craving scores while in treatment, nor in recidivism after treatment.     

Behavioral naltrexone therapy: an integrated treatment for opiate dependence

Treatment of opiate dependence with naltrexone has been limited by poor compliance. Behavioral Naltrexone Therapy (BNT) was developed to promote adherence to naltrexone and lifestyle changes supportive of abstinence, by incorporating components from empirically validated treatments, including Network Therapy with a significant other to monitor medication compliance, the Community Reinforcement Approach, and voucher incentives. An overview is presented of the BNT treatment manual. In an uncontrolled Stage I trial (N = 47), 19% completed the 6-month course of treatment. Retention was especially poor in the subsample of patients who were using methadone at baseline (N = 18; 39% completed 1 month, none completed 6 months), and more encouraging among heroin-dependent patients (N = 29; 65% completed 1 month, 31% completed 6 months). Thus, attrition continues to be a serious problem for naltrexone maintenance, although further efforts to develop interventions such as BNT are warranted.     

Combination therapy with naltrexone and bupropion for obesity

INTRODUCTION: Although pharmacological treatments for obesity represent only one option in managing obesity, they are a useful tool in an otherwise extremely limited armamentarium. Naltrexone/bupropion combination therapy was developed by using technological advances that have improved our understanding of how the brain regulates body weight. AREAS COVERED: This review covers the development of naltrexone/bupropion combination therapy for obesity, as well as the published clinical trials on the safety and efficacy of the combination in overweight and obese humans. The effect of naltrexone/bupropion on food craving seems to be unique, and the implications of this finding for weight loss are discussed. EXPERT OPINION: Safety and tolerability issues seem to be manageable and consistent with the documented effects of each component. Appropriate patient management should address the mild sympathomimetic effect of bupropion, although the FDA has required that a cardiovascular outcomes study be conducted preapproval to determine the effects of long-term use of naltrexone/bupropion in an overweight/obese population. When used in conjunction with diet and exercise, the naltrexone/bupropion combination may be a useful treatment option for obesity, especially for overweight and obese adults who report difficulty controlling eating behavior and their response to food cravings.     

Marital and family therapy in alcoholism treatment

This synopsis of the outcome literature on marital and family treatment (MFT) drew three conclusions. First, intervening at the marital/family level with nonalcoholic family members can motivate an initial commitment to change in the alcoholic who is unwilling to seek help. Second, MFT alone, or with individual alcoholism treatment, produces better marital and/or drinking outcomes during the 6 months following treatment entry than methods that don't involve the spouse or other family members. The most promising MFT approach is behavioral marital therapy (BMT) that combines a focus on the drinking with work on other marital relationship issues via direct instigation of positive couple/family activities and teaching of communication and conflict resolution skills. Two BMT alcohol-focused methods have been used: a behavioral contract between alcoholic and spouse to maintain disulfiram ingestion; and "Alcohol-Focused Spouse Involvement," which rearranges reinforcement contingencies to decrease family behaviors that trigger or enable drinking and to increase positive reinforcement for sobriety. Third, studies of long-term maintenance suggest that BMT with an alcohol and relationship focus may reduce marital and/or drinking deterioration better than individual methods during long-term recovery. The following recommendations were made when to intervene at the level of the individual alcoholic only, at the marital/family level, or at both the individual and marital/family levels: (a) Intervene only at the individual level when the alcoholic refuses consent to contact family members or the family refuses involvement. (b) Include adult family members who live with the alcoholic in the assessment process for all who consent.(ABSTRACT TRUNCATED AT 250 WORDS)     

Extended naltrexone and broad spectrum treatment or motivational enhancement therapy

Background  

Randomized clinical trials on the effectiveness of naltrexone (NTX) in the treatment of alcohol dependence have produced conflicting results. One possible explanation for these discrepancies may lie in the various psychosocial treatments for which NTX is an adjunct. The goal of this study was to examine the interplay between psychosocial treatment and duration of NTX.     

Readmissions for treatment for alcoholism

First admissions and readmissions for alcoholism have risen steeply in recent decades. This study looked at readmission histories for four cohorts of alcoholics first admitted to inpatient psychiatric treatment in 1967-68, 1973, 1977 or 1979. Over the twelve years the first cohort was observed, alcoholics on average spent 254 days in treatment and had 2.14 alcohol-related readmissions. However the distributions were very skewed: 50% stayed less than 92 days and 45.6% had no readmissions at all. All four cohorts yielded similar results over comparable time periods and all showed markedly skewed distributions reflecting the diversity of readmission histories among alcoholics. Policy decisions about alcoholism inpatient treatment must take account of this diversity.     

Individualized care for the treatment of alcoholism

Through a discussion of several case vignettes, the author emphasizes the utilization of an individually tailored treatment approach when working with people experiencing problem related to alcohol consumption. Patients may achieve abstinence without believing in the disease concept of alcoholism, and attending Alcoholics anonymous meetings need not always be a part of the treatment. Furthermore, for some patients, controlled drinking may be as desirable an outcome as abstinence. The importance of entertaining a multiplicity of perspectives when conducting clinical work with such patients is discussed.     

Potentiation of low dose ketamine effects by naltrexone: potential implications for the pharmacotherapy of alcoholism.

The interplay of opiate and NMDA glutamate receptors may contribute to psychosis, cognitive function, alcoholism, and substance dependence. Ketamine and ethanol block the NMDA glutamate receptor. The purpose of this randomized double-blind, placebo-controlled human laboratory study was to evaluate whether the interactive effects of drugs acting at opiate and NMDA glutamate receptors might partially explain the efficacy of naltrexone for the treatment of alcoholism, that is, whether naltrexone 25 mg pretreatment would modulate ketamine effects in healthy human subjects. Two groups of healthy subjects were studied. An initial group (n=31) received a perception-altering subanesthetic dose of ketamine (bolus of 0.23 mg/kg over 1 min followed by a 60-min infusion of 0.58 mg/kg or saline bolus and infusion). A second group (n=24) completed the same testing procedures, but received a subperceptual ketamine dose (bolus 0.081 mg/kg over 10 min followed by an infusion of 0.4 mg/kg/h). Ketamine produced positive symptoms, negative symptoms, emotional discomfort, and cognitive effects as measured by the Positive and Negative Syndrome Scale (PANSS) in a dose-related fashion. The lower ketamine dose produced subjective effects similar to two standard ethanol drinks, whereas the higher ketamine dose produced effects similar to five standard drinks. Although naltrexone produced no significant behavioral effects, it significantly magnified the increase in the total PANSS score produced by the lower subperceptual dose of ketamine, but not the higher perception-altering dose of ketamine. These data suggest that the interplay of opiate receptor antagonism and NMDA receptor antagonism may be relevant to the protective effects of naltrexone on alcohol consumption via potentiation of dysphoric effects associated with the NMDA receptor antagonist effects of ethanol. However, these data suggest that at levels of NMDA receptor antagonism associated with heavy drinking, this protective effect of naltrexone on drinking is no longer present.     

Psychological test results at three stages of inpatient alcoholism treatment.

Improvement in intellectual, perceptual-motor and personality functioning was observed in men alcoholics after 30 and 60 days of treatment. On the basis of results with the Minnesota Multiphasic Personality Inventory, four consistent personality clusters were identified.     

Acamprosate--a novel treatment for alcoholism

The properties of acamprosate (calcium acetylhomotaurate), a new remedy for the treatment of alcoholism, are reviewed. The efficacy of this drug has been verified by numerous clinical tests in West Europe. The pharmacological activity of acamprosate is related to the drug action upon central neuromediator systems. No side or addiction effects of the drug were reported. Data on the clinical and pharmacological characteristics of acamprosate are summarized.     

Bupropion/naltrexone fixed-dose combination for the treatment of obesity

The combination of bupropion and naltrexone is one of the most promising new possibilities for the treatment of obesity in an era of increasing prevalence of this disease and decreasing options for its pharmacological management. Although approved by FDA panel members, it was temporally rejected by the FDA afterwards, who demanded more cardiovascular safety data for its commercialization. This monograph will focus on the physiology involved in its mechanisms of action and results of clinical trials.     

New pharmacological approaches for the treatment of alcoholism

Pharmacological relapse prevention in alcoholism is a rather new clinical field with few drugs being available. Acamprosate, acting predominantly via glutamatergic pathways, and the opioid receptor antagonist naltrexone, were both shown to be efficient in improving rates for continuous abstinence, and not relapsing to heavy drinking in a number of clinical trials and meta-analyses. There are conflicting data on both drugs, especially for acamprosate, according to some recent US studies. However, overall, the evidence is good. Both drugs are approved in most European countries and the US. Efficacy data for disulfiram are mixed; it is a second-line medication compared with other drugs, and is probably most effective when used in a supervised setting. Recently, anticonvulsants including carbamazepine and topiramate have been discussed as possible anti-craving drugs, but there is still limited evidence for their efficacy. Although there is a significant comorbidity for alcoholism with affective disorder, anxiety and schizophrenia, relatively few controlled clinical trials have been performed in this area. Tricyclics have been found to be more effective than serotonin reuptake inhibitors in improving depressive symptoms in these patients.     

Investigational therapies for the pharmacological treatment of alcoholism

Introduction: Alcohol dependence is one of the most important psychiatric disorders leading to enormous harm in individuals and indeed within society. Yet, although alcohol dependence is a disease of significant importance, the availability of efficacious pharmacological treatment is still limited.

Areas covered: The current review focuses on neurobiological pathways that are the rationale for recent preclinical and clinical studies testing novel compounds that could be used as treatments for alcohol dependence. These neurobiological mechanisms include the: glutamatergic, dopaminergic and GABA mediated pathways as well as neuroendocrine systems. There is also an interest in the approaches for influencing chromatin structure.

Expert opinion: There are several compounds in Phase I and Phase II clinical studies that have produced potentially useful results for the treating alcoholism. Further evaluation is still necessary, and the implementation of Phase III studies will help to elucidate the usefulness of these compounds. It is important that personalized approaches (e.g., pharmacogenomics) are investigated in these later studies, as the efficacy of different compounds may vary substantially between subgroups of patients.     

New pharmacological approaches for the treatment of alcoholism

Pharmacological relapse prevention in alcoholism is a rather new clinical field with few drugs being available. Acamprosate, acting predominantly via glutamatergic pathways, and the opioid receptor antagonist naltrexone, were both shown to be efficient in improving rates for continuous abstinence, and not relapsing to heavy drinking in a number of clinical trials and meta-analyses. There are conflicting data on both drugs, especially for acamprosate, according to some recent US studies. However, overall, the evidence is good. Both drugs are approved in most European countries and the US. Efficacy data for disulfiram are mixed; it is a second-line medication compared with other drugs, and is probably most effective when used in a supervised setting. Recently, anticonvulsants including carbamazepine and topiramate have been discussed as possible anti-craving drugs, but there is still limited evidence for their efficacy. Although there is a significant comorbidity for alcoholism with affective disorder, anxiety and schizophrenia, relatively few controlled clinical trials have been performed in this area. Tricyclics have been found to be more effective than serotonin reuptake inhibitors in improving depressive symptoms in these patients.