A multicentre, randomized, double-blind, placebo-controlled trial of naltrexone in the treatment of alcohol dependence or abuse.

The opioid antagonist, naltrexone, is reported, in single centre studies, to improve the clinical outcome of individuals with alcohol dependence participating in outpatient psychosocial programmes. This is the first multicentre controlled study to evaluate the efficacy and safety of naltrexone as adjunctive treatment for alcohol dependence or abuse. Patients who met criteria for alcohol dependence (n = 169) or alcohol abuse (n = 6) were randomly assigned to receive double-blind oral naltrexone 50 mg daily (n = 90) or placebo (n = 85) for 12 weeks as an adjunct to psychosocial treatment. The primary efficacy variable was time to first episode of heavy drinking; secondary efficacy assessments included time to first drink, alcohol consumption, craving, and changes in the serum biological markers gamma-glutamyl transferase (GGT), and aspartate and alanine aminotransferases. Compliance was assessed by tablet counts and, in the naltrexone-treated group, by measurement of urinary concentrations of 6-ss-naltrexol. Forty-nine (58%) patients randomized to placebo and 53 (59%) randomized to naltrexone did not complete the study. In intention-to-treat analyses, there was no difference between groups on measures of drinking. The median reduction from baseline of serum GGT (P: < 0.05) and the reductions in alcohol craving (Obsessive and Compulsive Drinking Scale: OCDS) were greater in the naltrexone group (P: < 0.05), from approximately half-way through the study. Of 70 patients (35 placebo; 35 naltrexone) who met an a priori definition of compliance (80% tablet consumption, attendance at all follow-up appointments), those allocated to naltrexone reported consuming half the amount of alcohol (P: < 0.05), had greater median reduction in serum GGT activity (P: < 0.05), and greater reduction in alcohol craving (OCDS total score: P: < 0.05; Obsessive subscale score: P: < 0.05), compared to patients in the placebo group. Use of naltrexone raised no safety concerns. Naltrexone is effective in treating alcohol dependence/abuse in conjunction with psychosocial therapy, in patients who comply with treatment.

United Kingdom Multicentre Acamprosate Study (UKMAS): a 6-month prospective study of acamprosate versus placebo in preventing relapse after withdrawal from alcohol.

A 6-month randomized controlled study of acamprosate versus placebo in preventing relapse following withdrawal from alcohol was undertaken in 20 centres throughout the UK. Patients diagnosed as alcohol-dependent and detoxified within the preceding 5 weeks were randomly assigned to treatment with either acamprosate (A) 666 mg three times/day or identical placebo (P). A total of 664 patients were screened; 581 were entered into the treatment phase. One-third were episodic drinkers, 84% were male, 44% were unmarried and 48% were unemployed. Medication was first taken on average 24 days after the start of detoxification; 32% of patients had already relapsed by this time. The 6-month study period was completed by 35% of patients; adverse events led to withdrawal of a further 14% (A) and 9% (P) respectively. Compliance was poor in that, by the end of the second week, only 57% of patients were judged to be taking at least 90% of their tablets. The mean total of abstinent days achieved was 77 (A) and 81 (P). Complete abstinence for 6 months was achieved by 12% (A) and 11% (P); drinking remained within controlled limits in a further 3% (A) and 6% (P). An effect of acamprosate on consumption was not seen when subgroups, including those defined by the Lesch typology, were analysed separately. However, the mean percentage reduction in craving for alcohol measured on a visual analogue scale was greater in the acamprosate, than placebo, patients at week 2 and week 4 (P<0.001) and the mean decrease in the Hamilton Anxiety score at the 4th week was greater in the acamprosate than placebo patients (P = 0.017). In comparison with other published trials of acamprosate, patients started study medication after a longer time following detoxification, had more often recommenced drinking before medication was started and had a higher drop-out rate, and this might have contributed to the lack of a treatment effect in this study.

Place of work, communities and municipalities.

The Paris conference recognized that although national social policy and international research were undoubtedly important, a local dimension to research action and planning was essential. The potential for community and municipal action was illustrated in a number of papers which are summarized here. It was also the subject of a publication in the series associated with the European Alcohol Action Plan. The work-place was taken as a significant microcosm of a community, where healthy company policy and an enlightened approach to providing early help and support to individuals with alcohol-related problems is particularly beneficial.

The SECCAT Survey: II. The Alcohol Related Problems Questionnaire as a proxy for resource costs and quality of life in alcoholism treatment. Study of Socio-Economic Consequences and Costs of Alcoholism and Treatment.

An interview was obtained with 212 patients who had, at a point 12 months previously, been in contact with an alcohol problems clinic. Quality of life (SF-36) was measured and for the preceding 6 months the cost of health and social service resource use was estimated, together with the total abstinent (or controlled drinking) days accrued. Alcohol related health, personal and social problems experienced during that period were elicited using a brief 11-item questionnaire, the Alcohol Related Problems Questionnaire (ARPQ). The estimate of costs correlated more strongly with the ARPQ score (r = -0.32, P = 0.0001) than with abstinent days (r = 0.03, n.s.) or controlled drinking months (r = -0.21, P = 0.002). The lack of relation of total abstinent days to cost is partly because abstainers tended to use considerable alcohol problems clinic resources. ARPQ scores indicating more problems were associated with lower quality of life. The ARPQ can serve as a proxy for resource use and quality of life in alcoholism treatment.

The SECCAT survey: I. The costs and consequences of alcoholism.

The SECCAT survey assessed the Socio-Economic Costs and Consequences of Alcoholism Treatment. Basic demographic and health service resource use data (for a previous 6-month period) were obtained fro a cohort of 586 eligible patients who had had treatment at the Alcohol Problems Clinic (APC) in Edinburgh. The cohort was 75% male with a mean age of 46.0 years. Seventy-six per cent had an initial diagnosis of alcohol dependence and 21% alcohol abuse. Use of health services was highly variable. Thirty-six per cent agreed to be interviewed to provide data on their level of abstinence, on resource use, on quality of life (SF-36), on socio-economic characteristics and key adverse events. These 212 individuals had similar age and sex ratios to the full cohort, but alcohol abusers were under-represented. Nineteen patients reported no days of abstinence and 41 were abstinent over the whole 6-month period. Patients experienced a much poorer quality of life than a normal population in terms of all dimensions of the SF-36. The average total health care costs of the interviewed patients were 1134 pounds of which 38% were related to treatment at the APC. Analysis suggests that alcohol-dependent patients make substantially more costly use of resources than abusers and experience a much poorer quality of life. No clear relationship of cost to degree of abstinence has been found. There is a clear and consistent relationship of SF-36 scores and drinking behavior.

Preventive strategies for alcohol-related problems.

Preventive strategies for alcohol-related problems need to be in keeping with their socio-political context. Prohibition is inappropriate except where it has widespread support within the culture. Preventive strategies focus on the population and/or high risk groups and behaviours. Primary prevention can be achieved by control policies, education and provision of alternatives. Fiscal measures are of proven value. Legislative approaches influence availability and context of drinking, such as drinking and driving. Advertising control, server training and server liability are further approaches. Encouraging the provision of alternative beverages and promoting alcohol-free environments is a further approach which should be seen as part of an integrated community response. Secondary prevention linked with early recognition of hazardous drinking at primary level is of known efficacy and would form part of a coordinated strategy.

Disulfiram treatment of alcoholism.

To assess the efficacy of supervised disulfiram as an adjunct to out-patient treatment of alcoholics, a randomised, partially blind, six-month follow-up study was conducted in which 126 patients received 200 mg disulfiram or 100 mg vitamin C under the supervision of a nominated informant. In the opinion of the (blinded) independent assessor, patients on disulfiram increased average total abstinent days by 100 and patients on vitamin C by 69, thus enhancing by one-third this measure of treatment outcome. Mean weekly alcohol consumption was reduced by 162 units with disulfiram, compared with 105 units with vitamin C, and the disulfiram patients reduced their total six-month alcohol consumption by 2572 units compared with an average reduction of 1448 units in the vitamin C group. Serum gamma-GT showed a mean fall of 21 IU/I in patients on disulfiram but rose by a mean of 13 IU/I with vitamin C. Unwanted effects in the disulfiram group led to a dose reduction in seven patients and to treatment withdrawal in four (and in one vitamin C patient). Two-thirds of the disulfiram group asked to continue the treatment at the end of the study. There were no medically serious adverse reactions.

Consistency of reported levels of alcohol-related problems in the community.

Regular drinkers identified in a general population survey of adults in the Lothian region were followed up 3 or 4 years later, with respect to alcohol-related problems. Using a variety of analytic methods, a moderate degree of temporal consistency in problems was found, for total number of problems, and for individual problems, with feeling ashamed of having done something while drunk being the most consistent.

Comparison of two benzodiazepines in the treatment of alcohol withdrawal: effects on symptoms and cognitive recovery.

Forty newly admitted alcohol-dependent patients were randomly allocated to equivalent 6-day regimes of either lorazepam or diazepam, to compare involvement in physical, emotional and cognitive state during the first 8 days in hospital. Diazepam provided a more comfortable withdrawal period and was associated with slightly better cognitive functioning on the eighth day.

Medical admissions in men: the risk among drinkers.

Information on alcohol consumption was elicited by the same method from men in a general population survey and from male medical inpatients in a hospital serving that population. A measure of risk controlling for age, the logarithm of the odds ratio, showed that for liver disorders, upper gastrointestinal disorders, myocardial infarction, other cardiovascular disorders, and respiratory disorders, rising consumption of alcohol was related to increased risk of hospital admission relative to abstention. The risk of admission for the remaining heterogeneous category of disorders was lower than that for abstention, perhaps reflecting the effect of chronic illness on drinking habits, and also suggesting that the link between alcohol consumption and medical diagnoses is not simply due to greater frankness about drinking in hospital inpatients.