• Seventy male alcohol-dependent patients participated in a 12-week, double-blind, placebo-controlled trial of naltrexone hydrochloride (50 mg/d) as an adjunct to treatment following alcohol detoxification. Subjects taking naltrexone reported significantly less alcohol craving and days in which any alcohol was consumed. During the 12-week study, only 23% of the naltrexone-treated subjects met the criteria for a relapse, whereas 54.3% of the placebo-treated subjects relapsed. The primary effect of naltrexone was seen in patients who drank any alcohol while attending outpatient treatment. Nineteen (95%) of the 20 placebo-treated patients relapsed after they sampled alcohol, while only eight (50%) of 16 naltrexone-treated patients exposed to alcohol met relapse criteria. Naltrexone was not associated with mood changes or other psychiatric symptoms. Significant side effects (nausea) occurred in two nalterxonetreated subjects, and one naltrexone-treated subject complained of increased pain from arthritis. These results suggest that naltrexone may be a safe and effective adjunct to treatment in alcohol-dependent subjects, particularly in preventing alcohol relapse.

Naltrexone in the treatment of alcohol dependence

ContextAlcohol dependence treatment may include medications, behavioral therapies, or both. It is unknown how combining these treatments may impact their effectiveness, especially in the context of primary care and other nonspecialty settings.ObjectivesTo evaluate the efficacy of medication, behavioral therapies, and their combinations for treatment of alcohol dependence and to evaluate placebo effect on overall outcome.Design, Setting, and ParticipantsRandomized controlled trial conducted January 2001-January 2004 among 1383 recently alcohol-abstinent volunteers (median age, 44 years) from 11 US academic sites with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnoses of primary alcohol dependence.InterventionsEight groups of patients received medical management with 16 weeks of naltrexone (100 mg/d) or acamprosate (3 g/d), both, and/or both placebos, with or without a combined behavioral intervention (CBI). A ninth group received CBI only (no pills). Patients were also evaluated for up to 1 year after treatment.Main Outcome MeasuresPercent days abstinent from alcohol and time to first heavy drinking day.ResultsAll groups showed substantial reduction in drinking. During treatment, patients receiving naltrexone plus medical management (n = 302), CBI plus medical management and placebos (n = 305), or both naltrexone and CBI plus medical management (n = 309) had higher percent days abstinent (80.6, 79.2, and 77.1, respectively) than the 75.1 in those receiving placebos and medical management only (n = 305), a significant naltrexone × behavioral intervention interaction (P = .009). Naltrexone also reduced risk of a heavy drinking day (hazard ratio, 0.72; 97.5% CI, 0.53-0.98; P = .02) over time, most evident in those receiving medical management but not CBI. Acamprosate showed no significant effect on drinking vs placebo, either by itself or with any combination of naltrexone, CBI, or both. During treatment, those receiving CBI without pills or medical management (n = 157) had lower percent days abstinent (66.6) than those receiving placebo plus medical management alone (n = 153) or placebo plus medical management and CBI (n = 156) (73.8 and 79.8, respectively; P<.001). One year after treatment, these between-group effects were similar but no longer significant.ConclusionsPatients receiving medical management with naltrexone, CBI, or both fared better on drinking outcomes, whereas acamprosate showed no evidence of efficacy, with or without CBI. No combination produced better efficacy than naltrexone or CBI alone in the presence of medical management. Placebo pills and meeting with a health care professional had a positive effect above that of CBI during treatment. Naltrexone with medical management could be delivered in health care settings, thus serving alcohol-dependent patients who might otherwise not receive treatment.Trial Registrationclinicaltrials.gov Identifier: NCT00006206

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Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence: The COMBINE Study: A Randomized Controlled Trial

Background: The Alcohol Use Disorders Identification Test Consumption (AUDIT-C) questions have been previously validated as a 3-item screen for alcohol misuse and implemented nationwide in Veterans Affairs (VA) outpatient clinics. However, the AUDIT-C's validity and optimal screening threshold(s) in other clinical populations are unknown.

Methods: This cross-sectional validation study compared screening questionnaires with standardized interviews in 392 male and 927 female adult outpatients at an academic family practice clinic from 1993 to 1994. The AUDIT-C, full AUDIT, self-reported risky drinking, AUDIT question #3, and an augmented CAGE questionnaire were compared with an interview primary reference standard of alcohol misuse, defined as a Diagnostic and Statistical Manual, 4th ed. alcohol use disorder and/or drinking above recommended limits in the past year.

Results: Based on interviews with 92% of eligible patients, 128 (33%) men and 177 (19%) women met the criteria for alcohol misuse. Areas under the receiver operating characteristic curves (AUROCs) for the AUDIT-C were 0.94 (0.91, 0.96) and 0.90 (0.87, 0.93) in men and women, respectively (p=0.04). Based on AUROC curves, the AUDIT-C performed as well as the full AUDIT and significantly better than self-reported risky drinking, AUDIT question #3, or the augmented CAGE questionnaire (p-values <0.001). The AUDIT-C screening thresholds that simultaneously maximized sensitivity and specificity were ≥4 in men (sensitivity 0.86, specificity 0.89) and ≥3 in women (sensitivity 0.73, specificity 0.91).

Conclusions: The AUDIT-C was an effective screening test for alcohol misuse in this primary care sample. Optimal screening thresholds for alcohol misuse among men (≥4) and women (≥3) were the same as in previously published VA studies.

AUDIT-C as a Brief Screen for Alcohol Misuse in Primary Care

A clinical practice guideline for treating tobacco use and dependence: 2008 update. A U.S. Public Health Service report

Telephone services can provide information and support for smokers. Counselling may be provided proactively or offered reactively to callers to smoking cessation helplines. Objectives To evaluate the effect of proactive and reactive telephone support via helplines and in other settings to help smokers quit. Randomized or quasi-randomized controlled trials in which proactive or reactive telephone counselling to assist smoking cessation was offered to smokers or recent quitters were used. Sixty-five trials met the inclusion criteria. Among smokers who contacted helplines, quit rates were higher for groups randomized to receive multiple sessions of proactive counselling (nine studies, >24,000 participants, risk ratio (RR) for cessation at longest follow up 1.37, 95% confidence interval (CI) 1.26 to 1.50). There was mixed evidence about whether increasing the number of calls altered quit rates but most trials used more than two calls. Two studies comparing different counselling approaches during a single quitline contact did not detect significant differences. Of three studies that provided access to a hotline two detected a significant benefit and one did not. Telephone counselling not initiated by calls to helplines also increased quitting (44 studies, >24,000 participants, RR 1.29, 95% CI 1.20 to 1.38). In the subgroup of studies offering 1-2 calls the effect was small and not significant. A further seven studies were too diverse to contribute to meta-analyses and are discussed separately.

Telephone counselling for smoking cessation.

OBJECTIVE: Neuropsychiatric symptoms are commonly associated with chronic hepatitis C virus infection, its sequelae, and its treatment. In particular, interferon, a primary component of treatment for chronic hepatitis C, has been strongly associated with depressive symptoms. This review summarizes current knowledge about the etiology, course, and treatment of neuropsychiatric problems associated with hepatitis C and interferon alpha (IFN-α) treatment. METHOD: Studies were identified by computerized searches, and further references were obtained from bibliographies of the reviewed articles. RESULTS: Chronic infection with the hepatitis C virus is a common and growing problem, often affecting persons with psychiatric and substance use problems. Although changes in cognition, mood, and personality have been described in association with hepatitis C and with IFN-α treatment, there has been little systematic study of these changes. CONCLUSIONS: Psychiatrists should become familiar with the clinical spectrum as...

Neuropsychiatric Symptoms Associated With Hepatitis C and Interferon Alpha: A Review

A Prospective Study of Neuropsychiatric Symptoms Associated With Interferon-α-2b and Ribavirin Therapy for Patients With Chronic Hepatitis C

Objective: Fear of jeopardizing drinking outcomes has resulted in a reluctance to treat tobacco dependence concurrently with alcohol dependence, in spite of the high prevalence of smoking among patients with alcohol dependence. The objective of this study was to compare the effects of smoking treatment and intensive treatment for alcohol dependence, delivered concurrently, with delayed smoking treatment on smoking and alcohol use. Method: For the study, 1,943 patients in intensive treatment for alcohol dependence or abuse were screened for participation. Of these, 499 smokers were enrolled and randomized to concurrent (during alcohol treatment) or delayed (6 months later) smoking intervention. The smoking intervention included individual behavioral counseling and nicotine replacement. The main smoking outcome measure was 7-day point prevalent tobacco abstinence, and the main drinking outcome was 6-month prolonged abstinence from alcohol; both measured 18 months after study enrollment. Results: Participant...

A randomized trial of concurrent versus delayed smoking intervention for patients in alcohol dependence treatment.

Background Medically ill alcoholics often do not respond to conventional alcoholism treatment or decline physician referrals. Integrated outpatient treatment (IOT), a new treatment specifically designed for this population, combines comprehensive medical care with alcoholism interventions. Objective To compare the efficacy of IOT with that of standard treatment approaches. Methods One hundred five male veterans with severe medical complications caused by alcoholism and recent drinking were randomly assigned to receive IOT or referral to standard alcoholism and medical treatment and were evaluated over 2 years. Integrated outpatient treatment patients received medical care and alcoholism interventions once or twice monthly. Patients in the control group were referred for alcoholism treatment, but few accepted. However, patients in the control group did engage in outpatient medical care. Results At baseline, the mean±SD age of the control group was 57.2±10.0 years, compared with 52.8±11.5 years in the IOT group ( P =.04). The groups were well matched in other respects. The mean±SD number of visits over 2 years for the IOT patients was 42.2±29.1, compared with 17.4±15.6 for the control patients ( P P =.02). Nearly twice as many control patients (30% [n=16]) as IOT patients (18% [n=9]) died, but the results of Cox survival analysis were not significant. There were no differences in symptoms of alcohol dependence, quality of life, or life problems. The incremental cost of IOT was approximately $1100 per patient per year. Conclusions Standard medical care alone was surprisingly effective in inducing abstinence in surviving medically ill alcoholics. Integrated outpatient treatment significantly increased both engagement and abstinence for a modest annual cost. Further refinement and testing of IOT is indicated.

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A Randomized Trial of Integrated Outpatient Treatment for Medically Ill Alcoholic Men

We assessed the efficacy of lithium carbonate in the treatment of 457 male alcoholics in a double-blind, placebo-controlled Department of Veterans Affairs Cooperative Study. Alcoholics either without depression or with a history of major depression, current major depression, or dysthymic disorder were studied. Two hundred eighty-six alcoholics without depression and 171 alcoholics with depression began the 52-week outpatient study; 172 alcoholics (60.1%) without depression and 108 alcoholics (63.2%) with depression completed the study. Among both all alcoholics who began the study and a subgroup who completed the study, no significant differences between alcoholics who took lithium and those who took placebo were found for the following outcome measures: number of alcoholics abstinent, number of days of drinking, number of alcohol-related hospitalizations, changes in rating of severity of alcoholism, and change in severity of depression. Similarly, no significant differences were found when only the 82 alcoholics compliant in taking lithium and the 89 alcoholics compliant in taking placebo were considered. In our study, lithium treatment did not affect the course of alcoholism in either depressed or nondepressed alcoholics. ( JAMA . 1989;262:1646-1652)

Mark L. Willenbring

Papers

Neuropsychiatric Symptoms Associated With Hepatitis C and Interferon Alpha: A Review

A Prospective Study of Neuropsychiatric Symptoms Associated With Interferon-α-2b and Ribavirin Therapy for Patients With Chronic Hepatitis C

A randomized trial of concurrent versus delayed smoking intervention for patients in alcohol dependence treatment.

A Randomized Trial of Integrated Outpatient Treatment for Medically Ill Alcoholic Men

Lithium Treatment of Depressed and Nondepressed Alcoholics