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Latest Research on Alcoholism
   
Alcohol Clin Exp Res. 2008 Mar 11 [Epub ahead of print]
Naltrexone and Cognitive Behavioral Therapy for the Treatment of Alcohol Dependence: Do Sex Differences Exist?
Baros AM, Latham PK, Anton RF.
Charleston Alcohol Research Center, MUSC, Charleston, South Carolina, USA.

Background: Sex differences in regards to pharmacotherapy for alcoholism is a topic of concern following publications suggesting naltrexone, one of the longest approved treatments of alcoholism, is not as effective in women as in men. This study was conducted by combining 2 randomized placebo controlled clinical trials utilizing similar methodologies and personnel in which the data was amalgamated to evaluate sex effects in a reasonable sized sample. Methods: A total of 211 alcoholics (57 female and 154 male) were randomized to the naltrexone/cognitive behavorial thearpy (CBT) or placebo/CBT arm of the 2 clinical trials analyzed. Baseline variables were examined for differences between sex and treatment groups via ANOVA for continuous variable or chi-squared test for categorical variables. All initial outcome analysis was conducted under an intent-to-treat analysis plan. Effect sizes for naltrexone over placebo were determined by Cohen's D (d). Results: The effect size of naltrexone over placebo for the following outcome variables was similar in men and women [% days abstinent (PDA) d = 0.36, % heavy drinking days (PHDD) d = 0.36, and total standard drinks (TSD) d = 0.36]. Only for men were the differences significant secondary to the larger sample size (PDA p = 0.03; PHDD p = 0.03; TSD p = 0.04). There were a few variables (GGT at week-12 change from baseline to week-12: men d = 0.36, p = 0.05; women d = 0.20, p = 0.45 and drinks per drinking day: men d = 0.36, p = 0.05; women d = 0.28, p = 0.34) where the naltrexone effect size for men was greater than women. In women, naltrexone tended to increase continuous abstinent days before a first drink (women d = 0.46, p = 0.09 and men d = 0.00, p = 0.44). Conclusions: The effect size of naltrexone over placebo appeared similar in women and men in our hands suggesting the findings of sex differences in naltrexone response might have to do with sample size and/or endpoint drinking variables rather than any inherent pharmacological or biological differences in response.

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Science. 2008 Mar 14;319(5869):1536-9. Epub 2008 Feb 14.
Neurokinin 1 receptor antagonism as a possible therapy for alcoholism.
George DT, Gilman J, Hersh J, Thorsell A, Herion D, Geyer C, Peng X, Kielbasa W, Rawlings R, Brandt JE, Gehlert DR, Tauscher JT, Hunt SP, Hommer D, Heilig M.
Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA.

Alcohol dependence is a major public health challenge in need of new treatments. As alcoholism evolves, stress systems in the brain play an increasing role in motivating continued alcohol use and relapse. We investigated the role of the neurokinin 1 receptor (NK1R), a mediator of behavioral stress responses, in alcohol dependence and treatment. In preclinical studies, mice genetically deficient in NK1R showed a marked decrease in voluntary alcohol consumption and had an increased sensitivity to the sedative effects of alcohol. In a randomized controlled experimental study, we treated recently detoxified alcoholic inpatients with an NK1R antagonist (LY686017; n = 25) or placebo (n = 25). LY686017 suppressed spontaneous alcohol cravings, improved overall well-being, blunted cravings induced by a challenge procedure, and attenuated concomitant cortisol responses. Brain functional magnetic resonance imaging responses to affective stimuli likewise suggested beneficial LY686017 effects. Thus, as assessed by these surrogate markers of efficacy, NK1R antagonism warrants further investigation as a treatment in alcoholism.

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Aust Fam Physician. 2008 Jan-Feb;37(1-2):16-9.
Alcohol intervention--what works?
Lee NK, Moore E.
Turning Point Alcohol and Drug Centre, Fitzroy, Victoria. nicole.lee@turningpoint.org.au

BACKGROUND: The majority of alcohol related problems in the community are managed in general practice. Screening and provision of brief interventions by general practitioners can impact on morbidity and mortality. General practitioners also play a central role in the management of alcohol dependence. OBJECTIVE: This article discusses risky drinking and the prevalence of alcohol problems. It describes evidence based approaches to alcohol related problems in primary care. DISCUSSION: Opportunistic screening and brief interventions in the general practice setting can have a sizeable impact on alcohol consumption rates among hazardous and harmful drinkers. They are low cost and easy and quick to implement. Patients with alcohol dependence will usually require a period of abstinence and more intensive treatment. They may benefit from alcohol pharmacotherapy, although the effects may be modest. Combining pharmacotherapy with referral to a psychologist for cognitive behavioural therapy may result in better outcomes than pharmacotherapy alone.

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Subst Abuse Treat Prev Policy. 2008 Jan 25;3(1):1 [Epub ahead of print]
Magnesium treatment in alcoholics: a randomized clinical trial.
Poikolainen K, Alho H.

ABSTRACT: BACKGROUND: Magnesium (Mg) deficiency is common among alcoholics. Earlier research suggests that Mg treatment may help to normalize elevated enzyme activities and some other clinically relevant parameters among alcoholics but the evidence is weak. METHODS: The effect of Mg was studied in a randomized, parallel group, double blind trial. The patients were first treated for alcohol withdrawal symptoms and then received for 8 weeks either 500 mg of Mg divided into two tablets or matching placebo. Measurements were made at the beginning and in the end of the Mg treatment period. The primary outcome was serum gamma-glutamyltransferase (S-GGT) activity; secondary outcomes included aspartate-aminotransferase (S-AST) and alanine-aminotransferase (S-ALT) activity. RESULTS: The number of randomized patients (completers) was 64 (27) in the treatment and 54 (31) in the control group. In intention-to-treat-analyses and in most analyses of study completers, there were no significant differences between the Mg-treated and placebo groups in the outcome variables. When baseline serum Mg level, coffee intake, and the number of unused Mg tablets were controlled for in a multivariate regression model, after-treatment serum Mg levels were found to be higher among the Mg-treated group than in the placebo group (t-test 3.334, df=53, p=0.002). After controlling for age, body weight, baseline alcohol intake, subsequent change in alcohol intake and baseline S-AST, the after-treatment S-AST levels were found to be lower among the Mg-treated group than in the placebo group (t-test 2.061, df=49, p=0.045). CONCLUSIONS: Mg treatment may speed up the S-AST decrease in compliant patients. This might decrease the risk of death from alcoholic liver disease. Trial registered at ClinicalTrials.gov ID NCT00325299.

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Recent Patents Anti-Infect Drug Disc. 2007 Jan;2(1):79-86.
Medication assisted treatment of drug abuse and dependence: global availability and utilization.
Kresina TF.
Division of Pharmacological Therapies, Center for Substance Abuse Treatment, Substance Abuse and Mental Health Services Administreation, Rockville, MD 20857, USA. tkresina@samhsa.gov

Clinical trials and clinical studies, using patented drugs and drugs off patent, provide data that impact the best treatment practices for substance abuse and dependence. In the United States, medications have been approved for use in the treatment of both alcohol and opioid dependence. Medications are used in the detoxification from drug abuse and dependence in the symptomatic relief of withdrawal. For long term treatment or medical maintenance treatment, medications eliminate the physiological effects of drug use by blocking drug-receptor binding in the brain. Therefore, patented drugs showing interactions with neurotransmitters in the brain, are attractive candidates for treatment efficacy trials. An effective long term treatment paradigm for reducing drug dependence is the combinatorial use of medications that block the effects of drug use with behavior change counseling and psychotherapy. Medications used for the long term treatment of opioid dependence are methadone, buprenorphine, and naltrexone. Pharmacotherapies used in the treatment of alcohol dependence include acamprosate, antabuse and naltrexone. A reliable indicator for successful treatment of drug dependence is time in treatment. Patients remain in long term treatment when they perceive that their health care environment is supportive and non-stigmatizing and with a good patient-provider relationship where their needs are identified and met. Additional medications are needed for individual comprehensive substance abuse treatment plans, particularly for individuals who abuse stimulants. Patented drugs remain an important source of candidate pharmacotherapies comprising medication assistant treatment, part of a comprehensive treatment plan for drug dependence that addresses the medical, social, and psychological needs of the patient. Adapting this drug treatment paradigm globally requires identifying and testing new drug candidates while building and changing programs to patient centered treatment programs that promote access to care and treatment and integrate medical, psychological, and social services.

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J Trauma. 2008 Jan;64(1):99-104.
Comparison of intravenous ethanol versus diazepam for alcohol withdrawal prophylaxis in the trauma ICU: results of a randomized trial.
Weinberg JA, Magnotti LJ, Fischer PE, Edwards NM, Schroeppel T, Fabian TC, Croce MA.
Section of Trauma, Burns, and Surgical Critical Care, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA.

BACKGROUND: Although benzodiazepines are the recommended first-line therapy for the prevention of alcohol withdrawal syndrome (AWS), the administration of intravenous ethanol as an alternative prophylactic agent persists in many surgical ICUs. Advocates of this therapy argue that ethanol provides effective prophylaxis against AWS without the excessive sedation observed with benzodiazepine therapy. No study to date, however, has compared the two therapies with regard to their sedative effects. The purpose of this study was to prospectively evaluate the efficacy of intravenous ethanol compared with benzodiazepines for the prevention of AWS with particular emphasis on the sedative effects of each therapy. METHODS: During a 15-month period, trauma patients admitted to the ICU with a history of chronic daily alcohol consumption greater than or equal to five beverage equivalents per day were prospectively randomized to one of two 4-day prophylactic regimens: intravenous ethanol infusion (EtOH) versus scheduled-dose diazepam (BENZO). Patients were evaluated with the Riker sedation-agitation scale, a 7-point instrument for the subjective assessment of both sedation (1 = unarousable) and agitation (7 = dangerous agitation). According to protocol, regimens were titrated to achieve and maintain a Riker score of 4 (calm and cooperative). Deviation from a score of 4 during the course of treatment was compared between groups. RESULTS: Fifty patients met study criteria and were randomized after obtainment of informed consent (EtOH, n = 26; BENZO, n = 24). Overall, the EtOH group had a significantly greater proportion of patients who deviated from a score of 4 during the course of treatment (p = 0.020). In both groups, the majority of deviation from a score of 4 reflected periods of under-sedation rather than over-sedation. One patient in the EtOH group failed treatment, requiring diazepam and haloperidol for control of AWS symptoms as per protocol, whereas no patient in the BENZO group failed treatment (p = NS). CONCLUSION: Concerning the prophylaxis of AWS, intravenous ethanol offers no advantage over diazepam with respect to efficacy or adverse sedative effects. The purported benefit of intravenous ethanol as a prophylactic agent against AWS was not evident.

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J Stud Alcohol Drugs. 2008 Jan;69(1):21-9.
Network support for drinking: an application of multiple groups growth mixture modeling to examine client-treatment matching.
Wu J, Witkiewitz K.
1007 West Harrison Street (M/C 285), Department of Psychology, University of Illinois at Chicago, Chicago, Illinois 60607.

ABSTRACT. Objective: The current study re-examined the Project MATCH (Matching Alcoholism Treatments to Client Heterogeneity) hypothesis that individuals with high network support for drinking would have the best treatment outcomes if they were assigned to twelve-step facilitation (TSF). Method: Drinking consequences, as measured by the Drinking Inventory of Consequences, was the primary outcome measure. Growth mixture models with multiple groups were used to estimate the drinking consequence trajectories of 952 outpatients during the 12 months following treatment for each of the three Project MATCH treatment conditions. Growth factors within latent trajectory classes were regressed on network support for drinking to assess whether treatment condition moderated the relationship between network support for drinking and drinking consequences over time. Results: Three latent classes were identified, representing low (n = 154, 16.2%), medium (n = 400, 42%), and high (n = 398, 41.8%) levels of drinking consequences. Classes did not differ across treatment groups. Greater network support for drinking predicted more drinking consequences over time but only for clients assigned to cognitive-behavioral therapy and motivational enhancement therapy, not TSF. Conclusions: This study provides further support for one of the original Project MATCH matching hypotheses: Clients with social networks supportive of drinking had better outcomes immediately after treatment if they were assigned to TSF. Because the original Project MATCH studies found this matching effect only at the 3-year follow-up, these results add validity to the network support for drinking matching effect. The study also provides additional evidence that accounting for heterogeneity in alcohol treatment outcomes is important for accurately estimating treatment effectiveness.

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J Stud Alcohol Drugs. 2008 Jan;69(1):5-13.
Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (The COMBINE Study): Examination of Posttreatment Drinking Outcomes.
Donovan DM, Anton RF, Miller WR, Longabaugh R, Hosking JD, Youngblood M; COMBINE Study Research Group.
Alcohol and Drug Abuse Institute, 1107 NE 45th Street, Suite 120, Seattle, Washington 98105-4631.

ABSTRACT. Objective: The aim of this study was to examine the efficacy of pharmacological and behavioral interventions across 1 year posttreatment in the COMBINE (Combining Medications and Behavioral Interventions) Study. Method: Alcohol-dependent individuals (N = 1,383; 428 women) recruited at 11 outpatient academic alcoholism-treatment clinics across the United States participated in a randomized, double-blind, placebo-controlled trial. They received 16 weeks of naltrexone (Revia) or acamprosate (Campral) or both medications and/or placebos in combination with medical management (MM), with or without combined behavioral intervention (CBI); one group received CBI without pills or MM. Drinking behavior and clinical status were assessed at the end of treatment (Week 16) and at Weeks 26, 52, and 68. Results: Prior treatment with active naltrexone, without active acamprosate or CBI or with active acamprosate plus CBI, and CBI with double placebo resulted in a significantly higher percentage of days abstinent than double placebos with no CBI (p < .05). Having received CBI was associated with positive clinical response posttreatment, compared with not having received CBI. Prior treatment with naltrexone increased the time to the first heavy-drinking day posttreatment (p = .03). No differences were found between patients who had received CBI without MM or pills and those having received MM and double placebo with or without CBI. No significant main effects for acamprosate were found on any of the outcome measures. Conclusions: Previous treatment with MM and either CBI or naltrexone, or both, but not acamprosate, was associated with sustained efficacy beyond discontinuation. Reasons for the maintained treatment gains with naltrexone and/or CBI and potential methods to extend them are discussed. (J. Stud. Alcohol Drugs 69: 5-13, 2008).

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Alcohol Clin Exp Res. 2007 Dec 12 [Epub ahead of print]
The Impact of Depressive Symptoms on Alcohol and Cigarette Consumption Following Treatment for Alcohol and Nicotine Dependence.
Kodl MM, Fu SS, Willenbring ML, Gravely A, Nelson DB, Joseph AM.
Center for Chronic Disease Outcomes Research, Minneapolis VA Medical Center, Minneapolis, Minnesota, USA.

Background: Although depression is common among alcohol and tobacco dependent patients, its impact on treatment outcomes is not well established. The purpose of this study was to examine the impact of depressive symptoms on abstinence from tobacco and alcohol after treatment for alcohol dependence and nicotine dependence. Methods: The Timing of Alcohol and Smoking Cessation Study (TASC) randomized adults receiving intensive alcohol dependence treatment, who were also smokers, to concurrent or delayed smoking cessation treatment. The sample consisted of 462 adults who completed depression and substance use (alcohol and smoking) assessments at treatment entry and 6, 12, and 18 months posttreatment. Longitudinal regression models were used to examine the relationships between depression and subsequent abstinence from alcohol and tobacco after baseline characteristics, including alcohol and smoking histories, were considered. Results: Depressive symptoms were prospectively related to nonabstinence from alcohol. Depressive symptoms at the previous assessment increased the odds of drinking at the subsequent time point by a factor of 1.67 (95% CI 1.14, 2.43), p < 0.01. Depressive symptoms were not significantly related to subsequent abstinence from cigarettes. Conclusions: Depression is an important negative predictor of the ability to maintain abstinence from alcohol within the context of intensive alcoholism and smoking treatment. It may be important to include depression-specific interventions for alcohol and tobacco dependent individuals to facilitate successful drinking treatment outcomes.

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Alcohol Clin Exp Res. 2007 Dec 7 [Epub ahead of print]
Naltrexone Is Associated With Reduced Drinking by Alcohol Dependent Patients Receiving Antidepressants for Mood and Anxiety Symptoms: Results From VA Cooperative Study No. 425, "Naltrexone in the Treatment of Alcoholism"
Krystal JH, Gueorguieva R, Cramer J, Collins J, Rosenheck R; The VA CSP No. 425 Study Team.
Alcohol Research Center, VA Connecticut Healthcare System, West Haven, Connecticut; NIAAA Center for the Translational Neuroscience of Alcoholism, Department of Psychiatry, Yale University School of Medicine, and Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, Connecticut, USA.

Background: It is not clear whether naltrexone is effective in reducing alcohol consumption among patients with clinically significant mood symptoms and whether naltrexone favorably interacts with antidepressant medications when they are co-prescribed. Methods: This study reflects a secondary analysis of the first 13 weeks of VA CSP #425, a study that evaluated the efficacy of naltrexone 50 mg/d in 627 alcohol dependent military veterans receiving Twelve Step Facilitation therapy at 20 VA Medical Centers. This study included patients with comorbid mood and anxiety disorders, providing they did not need treatment for these comorbid conditions at the time of study entry. Sixty patients developed sufficiently severe mood symptoms while on study medication that they required antidepressant treatment. This analysis evaluated whether the efficacy of naltrexone and placebo was influenced by the prescription of antidepressant medications to some study patients for their mood and anxiety symptoms. Results: In patients randomized to placebo (n = 209), prescription of antidepressants was associated with a significantly higher percentage of drinking days (lsmean = 24.4, se = 4.85 vs. lsmean = 12.9, se = 1.69, p = 0.02). Although the group of patients receiving naltrexone (n = 418) was larger than the group assigned to placebo, there were no significant differences in drinking-related outcomes in the groups who did or did not receive antidepressants (lsmean = 11.5, se = 1.18 vs. lsmean = 12.9, se = 1.69, p = 0.47). Among the group of patients receiving antidepressants, naltrexone prescription was associated with a reduction in the percent drinking days compared to placebo [lsmean = 10.1, se = 3.47 vs. lsmean = 24.4, se = 4.85, F(1,556) = 5.84, p = 0.02]. Conclusions: Further investigation will be needed to determine whether naltrexone is efficacious among depressed alcohol dependent patients and whether naltrexone and antidepressant medications show interactive efficacy for treating alcohol dependence.

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Lancet. 2007 Dec 8;370(9603):1915-22. Comment in: Lancet. 2007 Dec 8;370(9603):1884-5.
Effectiveness and safety of baclofen for maintenance of alcohol abstinence in alcohol-dependent patients with liver cirrhosis: randomised, double-blind controlled study.
Addolorato G, Leggio L, Ferrulli A, Cardone S, Vonghia L, Mirijello A, Abenavoli L, D'Angelo C, Caputo F, Zambon A, Haber PS, Gasbarrini G.
Institute of Internal Medicine, Catholic University of Rome, Rome, Italy. g.addolorato@rm.unicatt.it

BACKGROUND: Intervention to achieve alcohol abstinence represents the most effective treatment for alcohol-dependent patients with liver cirrhosis; however, anticraving drugs might worsen liver disease. We aimed to investigate the effectiveness and safety of baclofen in achieving and maintaining alcohol abstinence in patients with liver cirrhosis. METHODS: Between October, 2003, and November, 2006, 148 alcohol-dependent patients with liver cirrhosis were referred to the Institute of Internal Medicine, Rome, Italy. 84 were randomly allocated either oral baclofen or placebo for 12 weeks. Primary outcome was proportion of patients achieving and maintaining alcohol abstinence. Measures of this outcome were total alcohol abstinence and cumulative abstinence duration, which were assessed at outpatient visits. Relapse was defined as alcohol intake of more than four drinks per day or overall consumption of 14 or more drinks per week over a period of at least 4 weeks. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00525252. FINDINGS: Of 42 patients allocated baclofen, 30 (71%) achieved and maintained abstinence compared with 12 (29%) of 42 assigned placebo (odds ratio 6.3 [95% CI 2.4-16.1]; p=0.0001). The number of dropouts (termination of treatment) did not differ between the baclofen (6/42 [14%]) and placebo (13/42 [31%]) groups (p=0.12). Cumulative abstinence duration was about twofold higher in patients allocated baclofen than in those assigned placebo (mean 62.8 [SE 5.4] vs 30.8 [5.5] days; p=0.001). No hepatic side-effects were recorded. INTERPRETATION: Baclofen is effective at promoting alcohol abstinence in alcohol-dependent patients with liver cirrhosis. The drug is well tolerated and could have an important role in treatment of these individuals.

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Expert Rev Neurother. 2007 Nov;7(11):1465-77.
Acamprosate in the treatment of alcohol dependence: clinical and economic considerations.
Mason BJ, Crean R.
Committee on the Neurobiology of Addictive Disorders, Laboratory of Clinical Psychopharmacology, The Scripps Research Institute, 10550 North Torrey Pines Road, TPC 5, La Jolla, CA 92037, USA. mason@scripps.edu

Acamprosate has been commercially available in the USA since 2004 to treat alcohol dependence. Its safety and efficacy have been demonstrated in a number of clinical trials worldwide, which overall have shown significant improvements in abstinence compared with placebo. As with all alcoholism pharmacotherapies, acamprosate is used in conjunction with psychosocial interventions. One frequently described mechanism stipulates that acamprosate supports abstinence by normalizing the often protracted dysregulation of NMDA-mediated glutamatergic neurotransmission that follows chronic heavy alcohol use and withdrawal. This article reviews the clinical safety and efficacy of acamprosate, as well as results from recent pharmacoeconomic and human laboratory studies. These data elucidate the economic benefits of acamprosate, as well as its effects on cognition and alcohol-related sleep disturbances.

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J Clin Psychopharmacol. 2007 Aug;27(4):344-51.
A double-blind, placebo-controlled pilot trial of quetiapine for the treatment of Type A and Type B alcoholism.
Kampman KM, Pettinati HM, Lynch KG, Whittingham T, Macfadden W, Dackis C, Tirado C, Oslin DW, Sparkman T, O'Brien CP.
Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. kampman_k@mail.trc.upenn.edu

BACKGROUND: Atypical antipsychotics may be useful in the treatment of alcohol dependence. Human trials suggest that atypical antipsychotics may reduce alcohol craving and consumption, especially among patients with comorbid psychopathology. Therefore, these medications may be more useful for treating more severely affected alcoholics, such as patients with Type B alcoholism. Type B alcoholics are characterized by an early age of onset of problem drinking, high severity of alcohol dependence, increased psychopathology, and treatment-resistance. Quetiapine is an atypical antipsychotic with a favorable side effect profile, and may be a promising medication for the treatment of alcohol dependence, particularly Type B alcoholism. METHODS: Male and female alcoholics (33 Type A and 28 Type B) were included in a 12-week, double-blind, placebo-controlled trial. After detoxification, patients were randomized to receive quetiapine (n = 29), 400 mg/d at bedtime, or placebo (n = 32). The primary outcome measure was the quantity and frequency of alcohol consumption, measured by the timeline follow back. RESULTS: Forty-seven patients (77%) completed the trial, with no significant between-group differences in treatment retention. Nine quetiapine-treated patients (31%) maintained complete abstinence compared with 2 placebo-treated patients (6%) (chi(2) = 6.3, P = 0.012). There was a significant interaction between quetiapine and alcoholic subtype. As predicted, quetiapine- versus placebo-treated Type B alcoholics had significantly fewer days of drinking and fewer days of heavy drinking. Alcohol craving was also significantly reduced in quetiapine-treated compared with placebo-treated Type B alcoholics. Among Type A alcoholics, quetiapine provided no advantage over placebo in improving drinking outcomes. CONCLUSIONS: Quetiapine may be effective for the treatment of alcohol dependence, particularly in the more complicated Type B, early-onset alcoholics.

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Eur Arch Psychiatry Clin Neurosci. 2007 Jul 14; [Epub ahead of print]
Alcoholism in women: is it different in onset and outcome compared to men?
Diehl A, Croissant B, Batra A, Mundle G, Nakovics H, Mann K.
Dept. of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Mannheim, University of Heidelberg, J5, 68159, Mannheim, Germany, sucht@zi-mannheim.de.

Onset and course of alcohol dependence show gender related differences (telescoping effect) suggesting that women are more vulnerable to chronic alcohol consumption. This raises the question whether the differences are associated with a different treatment outcome as well. We hypothesized, that alcohol dependent women with a telescoping course show a less favourable treatment outcome compared to men. We investigated 212 alcohol dependent patients; matching 106 consecutively admitted women with 106 men drawn from a total sample of 343 male patients. The treatment program consisted of a 6 week inpatient treatment and 12 months of outpatient aftercare. We assessed milestone variables in development and course of alcoholism and carried out standardized diagnostic tests, physical and blood examinations to evaluate the course of the disease and treatment outcome. Overall, we confirm the telescoping effect, a faster progression in the course of alcoholism (developmental events and adverse consequences) in women compared to men ("telescoping effect"). However, despite the telescoping effect treatment outcome was similar in women and men. During the inpatient treatment program no alcohol relapse occurred. Throughout the 12 months outpatient treatment we found no significant differences in the survival analysis between women (283.29 +/- 11.26 days) and men (284.72 +/- 12.16 days). At the end of the 12 months both groups had an abstinence rate of approximately 50% and a drop-out rate of 33%.

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Addict Behav. 2007 Jun 9; [Epub ahead of print]
Long-term behavior in treated alcoholism: Evidence for beneficial carry-over effects of abstinence from smoking on alcohol use and vice versa.
Hintz T, Mann K.
Department for Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, University of Heidelberg, J5, 68159 Mannheim, Germany.

Co-dependence of alcohol and nicotine is quite frequent. Research results on the mutual influence one drug has on the other - i.e., on the further course of the dependence - has been inconclusive. Our primary aim is to investigate the natural course of smoking behavior in a long term follow-up study with alcohol-dependent patients who completed an inpatient treatment program. A sample of 139 out of originally 190 patients was successfully followed up 7 years after index alcohol treatment. After 7 years, 56% of patients (total surviving sample: 46%, 21 [11.1%] patients deceased during the follow-up time interval) were abstinent. Our results show that being a non-smoker at treatment entry is a predictor for alcohol abstinence 7 years later. The rate of non-smokers among the abstinent patients increased by 32%. Potential explanations for our findings lie in carry-over effects. Skills and insights gained in treatment of alcohol dependence could be instrumental in coping with smoking behavior as well. Non-smokers may have more functional coping abilities from the beginning. We conclude that it is warranted and recommendable to explore the willingness of alcohol-dependent patients to quit smoking and to offer them treatment options addressing this point.

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Exp Clin Psychopharmacol. 2007 Jun;15(3):272-81.
Family history and antisocial traits moderate naltrexone's effects on heavy drinking in alcoholics.
Rohsenow DJ, Miranda R, McGeary JE, Monti PM.
Providence Veterans Affairs Medical Center, Brown University School of Medicine, RI, USA. damaris_rohsenow@brown.edu

Naltrexone's (NAL) effects on alcohol consumption are generally modest, so identifying patients likely to benefit would improve treatment utility. Several studies indicate that potentially significant moderators of NAL's effects might include family history of alcohol problems (FH), age of onset of alcohol problems, degree of antisocial traits, and comorbid drug use. Data from 128 alcoholic patients enrolled in a 12-week NAL treatment study (50 mg/day) were reanalyzed to determine the role of FH, age of onset, antisocial traits, and comorbid drug use in NAL's treatment effects on heavy drinking days. Dichotomized FH, age of onset of alcohol problems, and comorbid cocaine or marijuana use had no interaction effect with medication. Percentage of relatives with problem drinking (family history percentage [FHP]) moderated the effects of NAL on drinking such that NAL resulted in lower drinking rates only for patients with higher FHP. Antisocial traits also moderated the effects of medication on drinking for patients compliant with =70% of medication. Patients with more antisocial traits had less heavy drinking on NAL than on placebo, whereas patients low on antisocial traits had no benefit from NAL. Covarying antisociality in regressions of drinking outcome on FHP showed that the effects of FHP were not attributable to antisociality. Thus, NAL may selectively benefit alcoholics with antisocial traits or 20% or more relatives with problem drinking. (c) 2007 APA, all rights reserved

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Am J Health Syst Pharm. 2007 Mar 1;64(5 Suppl 3):S5-11.
Understanding the health impact of alcohol dependence.
Cargiulo T.
University of Maryland School of Pharmacy, 20 North Pine Street, Baltimore, MD 21201, USA. tcargiulo@mail.co.ho.md.us

PURPOSE: To review the effects of alcohol dependence on physical and mental health. SUMMARY: Alcohol dependence is wide-spread among people of all ages and socioeconomic groups. Persons with alcohol dependence face enormous health consequences. Alcohol dependence is a major cause of mortality and is associated with psychiatric conditions, neurologic impairment, cardiovascular disease, liver disease, and malignant neoplasms. Psychiatric conditions associated with alcohol dependence include major depression, dysthymia, mania, hypomania, panic disorder, phobias, generalized anxiety disorder, personality disorders, any drug use disorder, schizophrenia, and suicide. Psychiatric comorbidity, in turn, is associated with alcohol-related symptoms of greater severity. Excessive alcohol consumption causes brain damage, as evidenced by brain imaging, and related neurologic deficits, including impairments in working memory, cognitive processing of emotional signals, executive functions, visuospatial abilities, and gait and balance. Whereas moderate alcohol consumption is cardioprotective, heavy drinking is associated with increased risks of hypertension, coronary heart disease, and ischemic stroke, possibly due to alcohol-induced sympathetic activation. Chronic excessive alcohol consumption is a strong risk factor for various types of cancer, particularly cancers of the aero-respiratory tract, but also cancers of the digestive system, liver, breast, and ovaries. Heavy drinking is associated with various forms of alcoholic liver disease, such as cirrhosis. (People with alcohol dependence die from cirrhosis at a much higher rate than is found in the general population.) Alcohol dependence also increases the risk of injury, possibly due to alcohol-related factors such as diminished coordination and balance, increased reaction time, and impaired attention, perception, and judgment. CONCLUSION: Alcohol dependence has numerous and serious ill effects on physical and mental health and represents a major public health burden.

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J Women Aging. 2007;19(1-2):31-48.
Women, aging, and alcohol use disorders.
Epstein EE, Fischer-Elber K, Al-Otaiba Z.
Center of Alcohol Studies, Rutgers-The State University of New Jersey, Piscataway, NJ 08854, USA. bepstein@rci.rutgers.edu

The increase in prevalence rates of alcohol use disorders in younger versus older cohorts of female drinkers is many times higher than the corresponding increase in prevalence rates for male drinkers. Thus, the number and impact of older female drinkers is expected to increase over the next 20 years as the disparity between men's and women's drinking rates decrease. Due to differences in metabolism of alcohol, women of all ages compared to men are at higher risk for negative physical, medical, social, and psychological consequences associated with at-risk and higher levels of alcohol consumption. Aging women face new sets of antecedents related to challenges in the middle and older adult phases of life, such as menopause, retirement, "empty nest," limited mobility, and illness. As women age, they are subject to an even greater physiological susceptibility to alcohol's effect, as well as to a risk of synergistic effects of alcohol in combination with prescription drugs. On the other hand, there is mixed research indicating that older women may benefit from the buffering effect of low levels of alcohol on hormonal declines associated with menopause, perhaps serving as a protective factor against Coronary Heart Disease and osteoporosis. However, with heavier drinking, these benefits are either reversed or eclipsed. In addition, any alcohol consumption increases the risk for breast cancer in older women. The possible beneficial effects of alcohol must be weighed with the fact that the research does not typically establish causality, that low-risk drinking equates to one standard drink per day, that there is a risk of progression towards alcohol dependence, and that there are alternate methods to gain the same benefits without the associated risks. Older women also experience unique barriers to detection of and treatment for alcohol problems. Current treatment options specifically for older women are limited, though researchers are beginning to address differential treatment response of older women, as well as development of elder women-specific treatment approaches. Treatment options include self-help/mutual peer support, which provides ancillary advantages, brief interventions in primary care settings, which have been demonstrated to be effective in reducing drinking levels, and cognitive behavioral techniques, which have been demonstrated to be useful; but more studies and larger samples are needed. Elder-specific treatments need to be appropriate in terms of content, to address the challenges associated with life stage, such as the loss of the parental role and widowhood, and in terms of process, such as delivery in a respectful therapeutic style and at a slower pace. Future directions in research should address the lack of assessment instruments, the risks of simultaneous use of alcohol and prescription medications, and the under-representation of older women in randomized trials of alcohol treatments.

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J Clin Psychopharmacol. 2007 Apr;27(2):160-5.
Naltrexone and disulfiram in patients with alcohol dependence and current depression.
Petrakis I, Ralevski E, Nich C, Levinson C, Carroll K, Poling J, Rounsaville B; VA VISN I MIRECC Study Group.
Department of Psychiatry, Yale University School of Medicine, Veterans Affairs Connecticut Healthcare System, West Haven Campus, West Haven, CT 06516, USA. ismene.petrakis@yale.edu

OBJECTIVE: Although disulfiram and naltrexone have been approved by the Food and Drug Administration for the treatment of alcoholism, no medications have been approved for individuals with alcohol dependence and comorbid psychiatric disorders. In particular, the effect of these medications on alcohol use outcomes and on specific psychiatric symptoms is still unknown in patients with the most common co-occurring disorder, major depression. METHOD: Two hundred fifty-four patients with a major Axis I psychiatric disorder and comorbid alcohol dependence were treated for 12 weeks in an outpatient medication study conducted at 3 Veterans Administration outpatient clinics. Randomization included (1) open randomization to disulfiram or no disulfiram, and (2) double-blind randomization to naltrexone or placebo. This resulted in 4 groups: (1) naltrexone alone, (2) placebo alone, (3) disulfiram and naltrexone, and (4) disulfiram and placebo. Primary outcomes were measures of alcohol use. Secondary outcomes included psychiatric symptoms assessed by the Hamilton Depression Rating Scale, alcohol craving, gamma-glutamyltransferase levels, and adverse events. RESULTS: One hundred thirty-nine subjects (54.7%) met the current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depression. There was no relationship between the diagnosis of depression and medication treatment on alcohol use outcomes, psychiatric symptoms, or the reporting of side effects for these medications. There was a significant interaction between diagnosis, medication group, and craving, where subjects with depression on disulfram reported lower craving over time than subjects with depression on naltrexone. CONCLUSIONS: The results suggest that disulfiram and naltrexone are safe pharmacotherapeutic agents for dually diagnosed individuals with depression for the treatment of alcohol use disorders.

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Alcohol Clin Exp Res. 2007 Apr;31(4):625-34.
Naltrexone and cognitive behavioral coping skills therapy for the treatment of alcohol drinking and eating disorder features in alcohol-dependent women: a randomized controlled trial.
O'Malley SS, Sinha R, Grilo CM, Capone C, Farren CK, McKee SA, Rounsaville BJ, Wu R.
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA. Stephanie.omalley@yale.edu

BACKGROUND: Despite important gender differences in drinking patterns, physiological effects of alcohol, and co-occurring psychiatric conditions, relatively little is known about the efficacy of naltrexone for the treatment of alcohol dependence in women. This study investigated the safety and efficacy of naltrexone in combination with Cognitive Behavioral Coping Skills Therapy (CBCST) in a sample of alcohol-dependent women, some with comorbid eating pathology. METHODS: One hundred three women meeting DSM-IV criteria for alcohol dependence (29 with comorbid eating disturbances) were randomized to receive either naltrexone 50 mg or placebo for 12 weeks in addition to weekly group CBCST. Subjects were enrolled between October 1995 and December 2000 at an outpatient research clinic. RESULTS: No significant differences were observed on the primary outcomes of time to first drinking day, time to first day of heavy drinking, or the percentage of participants who continued to meet the criteria for alcohol dependence. Secondary analyses revealed that naltrexone significantly delayed the time to the second (chi2=5.37, p=0.02) and third (chi2=4.35, p=0.04) drinking days among subjects who did not maintain abstinence from alcohol. Among those with eating disturbances, symptoms of eating pathology improved during treatment, but the effects did not differ according to medication condition. CONCLUSION: When used in conjunction with CBCST, naltrexone did not significantly improve drinking outcomes in the overall sample of alcohol-dependent women. However, naltrexone may be of benefit to women who are unable to maintain total abstinence from alcohol. For women with concurrent eating pathology, participation in treatment for alcoholism may be associated with improvements in eating pathology.

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Addiction. 2007 Apr;102(4):587-96. Epub 2007 Feb 15.
Does matching matter? Examining matches and mismatches between patient attributes and therapy techniques in alcoholism treatment.
Karno MP, Longabaugh R.
Integrated Substance Abuse Programs, University of California-Los Angeles, 11075 Santa Monica Boulevard, Los Angeles, CA 90025, USA. karno@ucla.edu

AIMS: This study assessed the predictive validity of the level of matching and mismatching between patients' personal attributes and aspects of outpatient psychotherapy they received. DESIGN AND PARTICIPANTS: On the basis of patient-by-treatment interactions observed for this sample in previous research, patients with alcohol abuse or dependence (n = 137) were designated retrospectively as being matched, unmatched or mismatched on each of four patient and treatment variable pairings. These pairings included (1) patient depressive symptoms and therapy emotion focus, (2) patient trait anger and therapy confrontation, (3) patient interpersonal reactance and therapy confrontation and (4) patient interpersonal reactance and therapy structure. MEASUREMENTS: Analyses of variance and logistic regression were used to assess the individual and additive effects of being matched and mismatched on the percentage of abstinent days (PDA) and recovery status in the year after treatment. FINDINGS: Being mismatched on any of the four patient-treatment pairings was a significant predictor of more frequent alcohol use post-treatment. Being matched on only two pairings predicted less frequent alcohol use, namely matches on therapy emotion focus with patient depressive symptoms and therapy structure with patient reactance. Matches appeared to optimize otherwise good outcomes, while mismatches had larger effect sizes and tended to predict relatively poor outcomes. The data supported the presence of an additive effect for mismatches on post-treatment PDA. The group with the most mismatches fared considerably worse than a group with fewer mismatches. Several matches and mismatches also predicted recovery status, with some support found for additive effects. CONCLUSIONS: Mismatches between patient attributes and treatment appear to have serious consequences, and this effect is magnified with multiple mismatches. Matches, on the other hand, while beneficial, may not be necessary to achieve good outcomes.

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Eur Neuropsychopharmacol. 2007 Mar 20; [Epub ahead of print]
The effect of naltrexone and acamprosate on cue-induced craving, autonomic nervous system and neuroendocrine reactions to alcohol-related cues in alcoholics.
Ooteman W, Koeter MW, Verheul R, Schippers GM, van den Brink W.
Amsterdam Institute for Addiction Research, Amsterdam, The Netherlands; Department of Psychiatry, Academic Medical Center University of Amsterdam, Amsterdam, The Netherlands.

Introduction: Acamprosate and naltrexone have been shown to be effective in relapse prevention of alcoholism. It is hypothesized that naltrexone exerts its effects primarily on cue-induced craving and neuroendocrine cue reactivity, whereas acamprosate exerts its effect primarily on autonomic nervous system reactions to alcohol-related cues. Experimental procedures: In a randomized double-blind experiment, 131 abstinent alcoholics received either acamprosate (n=56), naltrexone (n=52) or placebo (n=23) for three weeks and participated in two cue-exposure sessions: the first the day before and the second at the last day of medication. Results: Consistent with the hypotheses, naltrexone reduced craving more than acamprosate, and acamprosate reduced heart rate more than naltrexone. No medication effect was found on cue-induced cortisol. Discussion: The findings provide some evidence for differential effects of naltrexone and acamprosate: naltrexone may exert its effect, at least partly, by the reduction of cue-induced craving, whereas acamprosate may exert its effect, at least partly, by the reduction of autonomic nervous system reactions to alcohol-related cues.

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Biol Psychiatry. 2007 Mar 7; [Epub ahead of print]
Family History of Alcoholism Influences Naltrexone-Induced Reduction in Alcohol Drinking.
Krishnan-Sarin S, Krystal JH, Shi J, Pittman B, O'malley SS.
Department of Psychiatry Yale University School of Medicine, New Haven, Connecticut.

BACKGROUND: The purpose of this study was to examine the interactive effects of family history of alcoholism (FH+, FH-) and naltrexone dose (0, 50, 100 mg/day) on alcohol drinking. METHODS: Ninety-two, non-treatment-seeking alcohol-dependent participants received naltrexone daily for 6 days. On the 6th day, they participated in a laboratory paradigm involving exposure to a priming dose of alcohol followed by a 2-hour drinking period in which they made choices between consuming alcoholic drinks and receiving money. RESULTS: Total number of drinks consumed during the drinking period was significantly decreased by the 100-mg dose of naltrexone in FH+ drinkers. Secondary analyses in male drinkers (n = 70) indicated that 100 mg of naltrexone significantly decreased drinking in FH+ participants and increased drinking in FH- drinkers. CONCLUSIONS: These results suggest that family history of alcoholism might be a significant clinical predictor of response to naltrexone and that FH+ men are more likely to benefit from naltrexone therapy for alcohol drinking.

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Alcohol Clin Exp Res. 2007 Mar;31(3):436-42.
Ear acupuncture for alcohol withdrawal in comparison with aromatherapy: a randomized-controlled trial.
Kunz S, Schulz M, Lewitzky M, Driessen M, Rau H.
Clinic of Psychiatry and Psychotherapy Bethel, Ev. Hospital Bielefeld, Bielefeld, Germany.

BACKGROUND: There is increasing clinical acceptance of acupuncture as a treatment of substance-related disorders. Little is known about acupuncture as a treatment for the withdrawal syndrome in inpatient settings. We compared auricular needle acupuncture with aromatherapy in reducing the duration and severity of symptoms of alcohol withdrawal. METHODS: Inpatients undergoing alcohol withdrawal were randomly allocated to needle acupuncture (n=55) and aromatherapy (n=54). Both therapies were applied daily during the first 5 consecutive treatment days. The rating scale for the assessment of the alcohol-withdrawal syndrome (AWS scale) served as the main dependent variable and was applied daily during the first 5 days of the withdrawal. Further measures included a subjective visual analog scale of craving and the Self Assessment Manikin (SAM). RESULTS: Thirty-six of the 55 patients who received acupuncture, and 38 of the 54 patients who received aromatherapy, finished the study regularly. The groups differed in their initial self-reported arousal, which then served as a covariate in the further analyses. Neither the extent of craving nor of withdrawal symptoms differed between groups over the observation period. Self-rated arousal decreased in response to both treatments from days 1 to 2 (p<0.001) and within single days (p<0.001), and we found a significant interaction between pretreatment versus posttreatment and days (p<0.001). Interactions including between-subjects effects and intervention did not achieve the significance level. CONCLUSION: The results do not support the assumption of a superiority of acupuncture over the control therapy in its specific effects on alcohol withdrawal symptoms.

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J Stud Alcohol Drugs. 2007 Mar;68(2):238-47.
Building better cognitive-behavioral therapy: is broad-spectrum treatment more effective than motivational-enhancement therapy for alcohol-dependent patients treated with naltrexone?
Davidson D, Gulliver SB, Longabaugh R, Wirtz PW, Swift R.
Department of Psychiatry, Veterans Affairs Boston Healthcare System, 150 South Huntington Avenue, Boston, Massachusetts 02130, USA.

OBJECTIVE: The current study investigated the treatment effectiveness, during treatment, of a second-generation cognitive-behavioral therapy for alcoholism--broad-spectrum treatment (BST)--compared with motivational-enhancement therapy (MET), when both were offered in conjunction with a therapeutic dose of naltrexone (Revia). METHOD: One hundred forty-nine alcohol-dependent patients completed a 3-month randomized, controlled trial of BST and naltrexone versus MET and naltrexone. RESULTS: Patients receiving BST had a significantly higher percentage of days abstinent than patients receiving MET. The superior effect of BST is particularly strong in interaction with support for drinking, suggesting that the advantage of BST is worth the additional cost for patients whose psychosocial networks are supportive of continued drinking. This effect remains significant when controlling for pretreatment percentage of days abstinent. CONCLUSIONS: In aggregate, these findings suggest that it is either the combination of naltrexone and BST or the unique properties of BST that account for BST's superiority to MET and naltrexone. The results of this initial phase of the trial suggest that a second-generation cognitive-behavioral therapy such as BST may have a meaningful clinical advantage over brief interventions such as MET, at least when combined with naltrexone.

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Psychother Psychosom Med Psychol. 2007 Jan;57(1):32-8.
[One drink, one drunk--controlled drinking by alcoholics? 3-year-outcome after intensive outpatient treatment]
[Article in German]
Bottlender M, Spanagel R, Soyka M.
Psychiatrische Klinik und Poliklinik, Ludwig-Maximilians-Universitat Munchen. miriam.bottlender@btinternet.com

BACKGROUND: Up to now, controlled drinking as an alternative to abstinence for alcohol-dependents has been discussed controversially. In the present study we examined in a sample of alcohol-dependent patients whether or not controlled drinking is possible during a three years period following treatment. METHODS: 103 consecutively recruited alcohol-dependent participants (ICD-10) which took part in an abstinence-orientated outpatient treatment were re-interviewed 6, 12, 24, 36 months following treatment (follow-up ratio ca. 90 %). RESULTS: Analysis revealed that 43 % of patients were abstinent during total follow-up period and 12 % of patients were classified as improved at follow-up using the classification proposed by Feuerlein and Kufner. Of these patients, no patient at all was able to practise self-controlled drinking alcohol during the entire follow-up period. CONCLUSIONS: Only four patients had a drinking pattern similar to controlled drinking during a maximum period of 24 months. Though the primary aim of the evaluated outpatient clinic was to achieve abstinence and not controlled drinking, controlled drinking in alcohol-dependent patients nevertheless seems to be a rare phenomenon, which cannot be recommended. Moreover, recent animal models for alcoholism indicate alcoholism being an irreversible pattern.

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Subst Abuse Treat Prev Policy. 2006 Dec 18;1:35.
A follow up study on the efficacy of metadoxine in the treatment of alcohol dependence.
Guerrini I, Gentili C, Nelli G, Guazzelli M.
Bexley Substance Misuse Service, South London and Mausdley NHS Trust, London, UK. i.guerrini@ucl.ac.uk.

ABSTRACT: BACKGROUND: We carried out a three months follow-up study on the efficacy of metadoxine in a cohort of alcoholics admitted to the Alcohol misuse Long-term Treatment (ALT) Unit - University of Pisa (Italy). We analyzed the clinical data, psychometric tests and blood tests of 160 alcoholics on admission and after 3 months of treatment. We compared 58 pts treated with metadoxine (MET) with 102 pts who did not receive (NULL) any drug as an adjunct to the psycho-educational interventions provided by the ALT Unit. RESULTS: At follow-up, the patients in treatment with metadoxine showed a significant improvement in the rate of complete abstinence (44.8% vs. 21.6%; chi square: 8.45, df = 1, p < 0.0037). Furthermore, the number of drop-outs at three months of treatment was also significantly lower in the MET than in the NULL group (17% vs. 57%; chi square of 23.22, df = 1, p < 0.001). CONCLUSION: Our findings support the use of metadoxine in the management of alcohol dependence. However, randomized clinical trials are necessary to confirm and replicate them. This study raises the importance of identifying new pharmacological compounds effective on the outcome of alcoholism in order to help patients to best adhere to treatment programs and to prevent the development of mental and physical complications due to chronic and heavy use of alcohol.

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J Clin Psychopharmacol. 2006 Dec;26(6):610-25.
The status of naltrexone in the treatment of alcohol dependence: specific effects on heavy drinking.
Pettinati HM, O'Brien CP, Rabinowitz AR, Wortman SP, Oslin DW, Kampman KM, Dackis CA.
Center for the Study of Addictions, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6178, USA. Pettinati_H@mail.trc.upenn.edu

BACKGROUND: In almost 2 decades of naltrexone research for treating alcoholism, there have been 29 published randomized placebo-controlled trials of opioid antagonists, primarily naltrexone, for the treatment of alcohol dependence. The present review builds on prior systematic reviews while maximizing the number of included studies to date, for the purpose of resolving inconsistencies in naltrexone's reported efficacy across trials. Clinical trial results in this article are evaluated by the type of outcome measure used to determine naltrexone's treatment advantage, that is, measures related to reducing heavy drinking versus those related to increasing abstinence. METHODS: We conducted a Medline search to identify double-blind studies from 1990 to the present (2006) that evaluated the use of anopiate antagonist for the treatment of alcohol dependence. There were 29 studies identified, representing 5997 alcohol-dependent patients, which met our study inclusion criteria for this review. Studies were evaluated in this review on 4 prespecified drinking outcomes-2 related to "any drinking" and 2 related to "heavy or excessive drinking." RESULTS: In the treatment of alcohol dependence, we found that 19 (70%) of 27 clinical trials that measured reductions in "heavy or excessive drinking" demonstrated an advantage for prescribing naltrexone over placebo, whereas only 9 (36%) of 25 clinical trials that measured abstinence or "any drinking" found an advantage for medication over placebo. CONCLUSION: The majority of double-blind clinical trials in the literature favored prescribing naltrexone for alcohol dependence to reduce heavy drinking. This finding is consistent with our understanding of naltrexone's mechanism of action of decreasing excessive drinking by reducing the reward associated with drinking alcohol. Thus, we conclude that outcome measures related to heavy or excessive drinking are most relevant to defining naltrexone's therapeutic effects. Factors influencing naltrexone response (treatment adherence and distinct patient subgroups) are also discussed.

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Expert Opin Pharmacother. 2006 Dec;7(17):2341-53.
New pharmacological approaches for the treatment of alcoholism.
Soyka M, Roesner S.
Private Hospital Meiringen, P.O.Box 612, CH-3860 Meiringen, Switzerland. michael.soyka@pm-klinik.ch

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.

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Qual Health Res. 2006 Nov;16(9):1252-66.
"I thought there was no hope for me": a behavioral intervention for urban mothers with problem drinking.
de Guzman R, Leonard NR, Gwadz MV, Young R, Ritchie AS, Arredondo G, Riedel M.
Center for Drug Use and HIV Research, Institute for AIDS Research, National Development and Research Institutes, Inc., New York, USA.

In this article, the authors evaluate the effects of a behavioral intervention for mothers with problem drinking who were infected with, or at risk for, HIV. They randomly selected 25 mothers from a larger longitudinal randomized controlled intervention trial for a qualitative interview. The authors found that mothers' participation in the program was facilitated by the development of a strong therapeutic alliance with the intervention facilitator and the use of a harm reduction approach toward alcohol and/or drug abuse. Mothers also reported that training in coping skills and the emphasis on parent-adolescent relationships were beneficial for program engagement and behavior change. The authors conclude from these results that treatment approaches that take into account the complexity of urban mothers' lives and substance use patterns can successfully engage and treat these women at high risk for adverse outcomes.

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Expert Opin Pharmacother. 2006 Oct;7(15):2169-73.
Which treatment for alcohol dependence: naltrexone, acamprosate and/or behavioural intervention?
Doggrell SA.
School of Science, Faculty of Education, Health and Science, Charles Darwin University, Darwin, Northern Territory 0909, Australia. sheila.doggrell@cdu.edu.au

Alcoholism is the third leading cause of preventable mortality and morbidity in the US. In the COMBINE (Combined Pharmacotherapies and Behavioural Interventions) study, the co-primary end points were the percentage of days abstinent and the time to first heavy drinking day after 16 weeks, and 1 year. The biggest difference observed in COMBINE was that seen between combined behavioural intervention (CBI; percentage of abstinent days = 66.6%) and CBI and medical management with placebos (79.8%). This illustrated a major effect of the medical management of nine sessions and/or the placebo pills. Acamprosate had no effect alone or in combination with naltrexone. At 16 weeks with medical management, there were 75.1% of the patients who were abstinent for placebos, and this was improved by naltrexone, CBI, and naltrexone with CBI (80.6, 78.2 and 77.1%, respectively). There was a follow up after 1 year, which showed that, with medical management, the amount of those who were abstinent for placebos was 61.4%, and this was improved by naltrexone, CBI, and naltrexone with CBI (66.2, 66.6 and 67.3%, respectively), but this improvement no longer reached statistical significance. After 1 year, there was no difference between groups in the overall frequency of hospitalisation, emergency treatment for alcohol problems, use of medication for drinking or emotional problems and detoxification. Being part of a study for alcohol dependence is known to increase the percentage of abstinent days. In COMBINE, this percentage was high in the group having medical management and placebo pills, and naltrexone or additional behavioural therapy only had modest additional effects.

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J Psychoactive Drugs. 2006 Sep;38(3):211-7.
Comparing treatments of alcoholism on craving and biochemical measures of alcohol consumptionst.
Nava F, Premi S, Manzato E, Lucchini A.
Department of Addiction Medicine, Drug Abuse Unit (Ser.T.), Hospital of Castelfranco Veneto, Via Ospedale, 18, 31033 Castelfranco Veneto-Treviso, Italy. felnava@tin.it

An open randomized study was conducted to compare different treatments of alcoholism on ethanol intake, craving, and on biochemical measures of alcohol consumptions. Eighty-six alcoholics were abstinent for a mean of two weeks prior to random assignment to g-hydroxybutyrate (GHB, 50 mg/kg of body weight t.i.d), naltrexone (NTX, 50 mg/day) or disulfiram (DSF, 200 mg/ day) treatment for 12 months. All treatments were equally effective in reducing alcohol intake and in maintaining abstinence. In all patients, the treatments were able to reduce both craving and the altered biological markers of alcohol abuse. The maximum effects were observed in GHB-treated patients. The results of the present study suggest that GHB might act both as anticraving and cellular protector agent.
 

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