Naltrexone in the treatment of alcohol dependence.

BACKGROUND: Although naltrexone, an opiate-receptor antagonist, has been approved by the Food and Drug Administration for the treatment of alcohol dependence, its efficacy is uncertain. METHODS: We conducted a multicenter, double-blind, placebo-controlled evaluation of naltrexone as an adjunct to standardized psychosocial treatment. We randomly assigned 627 veterans (almost all men) with chronic, severe alcohol dependence to 12 months of naltrexone (50 mg once daily), 3 months of naltrexone followed by 9 months of placebo, or 12 months of placebo. All patients were offered individual counseling and programs to improve their compliance with study medication and were encouraged to attend Alcoholics Anonymous meetings. RESULTS: There were 209 patients in each group; all had been sober for at least five days before randomization. At 13 weeks, we found no significant difference in the number of days to relapse between patients in the two naltrexone groups (mean, 72.3 days) and the placebo group (mean, 62.4 days; 95 percent confidence interval for the difference between groups, -3.0 to 22.8). At 52 weeks, there were no significant differences among the three groups in the percentage of days on which drinking occurred and the number of drinks per drinking day. CONCLUSIONS: Our findings do not support the use of naltrexone for the treatment of men with chronic, severe alcohol dependence.

Determinants of functional outcome and healthcare costs in bipolar disorder: a high-intensity follow-up study.

BACKGROUND: Review of published studies reveals few data regarding determinants of the poor functional outcome and high healthcare costs that are characteristic of bipolar disorder. In order to identify potential mechanisms, critical to designing optimal treatment strategies, this longitudinal study investigated (a) the degree to which disease outcome is correlated with functional outcome and direct treatment costs, and (b) whether similar demographic or clinical characteristics predict disease and functional outcome and healthcare costs. METHODS: Disease and functional outcome were assessed in bimonthly structured interviews over 48 weeks in 43 outpatient veterans with bipolar disorder. Direct mental health treatment costs from the VA perspective were determined from the VA database and patient interview. Regression analysis was used to determine association among the three outcome domains, and to identify clinical or demographic variables that predicted each of the three domains. RESULTS: Functional outcome was correlated with depressive, but not manic, symptoms during follow-up. Costs were not correlated with any measure of disease or functional outcome. Several demographic, but not clinical, characteristics predicted functional outcome. In contrast, several clinical, but not demographic, characteristics predicted symptom status. No predictors were associated with direct treatment costs. LIMITATIONS: Subjects were predominantly male veterans of relatively homogeneous social class, followed prospectively for approximately one year in a clinic designed specifically to minimize barriers to care. CONCLUSIONS: Data from this and prior studies indicate that ongoing depressive symptoms are strongly associated with functional outcome, although substantial variance remains unexplained. Optimal models to explain functional outcome and healthcare costs will need to address factors besides simply disease severity and chronicity. The authors present a heuristic paradigm for understanding both the research and therapeutic aspects of these findings.

Prevention and Treatment of Hypertension Study (PATHS): effects of an alcohol treatment program on blood pressure.

OBJECTIVE: To determine whether blood pressure is reduced for at least 6 months with an intervention to lower alcohol intake in moderate to heavy drinkers with above optimal to slightly elevated diastolic blood pressure, and whether reduction of alcohol intake can be maintained for 2 years. DESIGN: A randomized controlled trial. METHODS: Six hundred forty-one outpatient veterans with an average intake of 3 or more alcoholic drinks per day in the 6 months before entry into the study and with diastolic blood pressure 80 to 99 mm Hg were randomly assigned to a cognitive-behavioral alcohol reduction intervention program or a control observation group for 15 to 24 months. The goal of the intervention was the lower of 2 or fewer drinks daily or a 50% reduction in intake. A subgroup with hypertension was defined as having a diastolic blood pressure of 90 to 99 mm Hg, or 80 to 99 mm Hg if recently taking medication for hypertension. RESULTS: Reduction in average weekly self-reported alcohol intake was significantly greater (P<.001) at every assessment from 3 to 24 months in the intervention group vs the control group: levels declined from 432 g/wk at baseline by 202 g/wk in the intervention group and from 445 g/wk by 78 g/wk in the control group in the first 6 months, with similar reductions after 24 months. The intervention group had a 1.2/0.7-mm Hg greater reduction in blood pressure than the control group (for each, P = .17 and P = .18) for the 6-month primary end point; for the hypertensive stratum the difference was 0.9/0.7 mm Hg (for each, P = .58 and P = .44). CONCLUSIONS: The 1.3 drinks per day average difference between changes in self-reported alcohol intake observed in this trial produced only small nonsignificant effects on blood pressure. The results from the Prevention and Treatment of Hypertension Study (PATHS) do not provide strong support for reducing alcohol consumption in nondependent moderate drinkers as a sole method for the prevention or treatment of hypertension.