Physicians' opinions about medications to treat alcoholism

Aims Medications play a limited role in the treatment of alcoholism. This paper examines physicians’ opinions about and use of two alcoholism medications currently approved in the US—disulfiram and naltrexone—and one alcoholism medication—acamprosate—that might be approved. Design A total of 1388 substance abuse specialist physicians who were members of the American Academy of Addiction Psychiatry or the American Society of Addiction Medicine completed a questionnaire in 2001 (65% response rate). Findings The average percentages of physicians’ patients with alcoholism who were prescribed the following medications were: 13% (naltrexone), 9% (disulfiram), 46% (antidepressants) and 11% (benzodiazepines). Almost all physicians had heard of naltrexone and disulfiram, but their self‐reported level of knowledge about these medications was lower than for antidepressants. Physicians estimated that naltrexone had a small‐to‐medium effect size, which was similar in magnitude to the effect size reported in recent meta‐analyses of randomized clinical trials. Physicians identified the following three courses of action as the most likely to result in greater use of medications to treat alcohol dependence: more research to develop new medications (33%), more education of physicians about existing medications (17%), and increased involvement of physicians in alcoholism treatment (17%). Conclusions Physicians’ low rate of use of naltrexone may reflect its small‐to‐medium effect size.     

Effects of Disulfiram on Positron Emission Tomography and Neuropsychological Studies in Severe Chronic Alcoholism

Disulfiram is an aldehyde dehydrogenase inhibitor that is widely used as an adjunctive agent in the treatment of patients with severe chronic alcoholism. Recent positron emission tomography (PET) studies of local cerebral metabolic rates for glucose (ICMRglc) and benzodiazepine receptor binding in alcoholic patients have shown regional cerebral abnormalities; however, some of the patients were studied while receiving disulfiram, which could influence the biochemical processes under investigation. In a retrospective investigation, we examined the influence of disulfiram administration on the results of PET studies of ICMRglc and benzodiazepine receptor binding and neuropsychological tests of cognition and executive function in patients with severe chronic alcoholism. [¹⁸F]Fluorodeoxyglucose was used to measure ICMRglc in 48 male patients, including 11 receiving and 37 not receiving disulfiram in therapeutic doses. [¹¹C]Flumazenil was used to measure benzodiazepine receptor binding in 17 male patients, including 3 receiving and 14 not receiving disulfiram. All patients studied with FMZ were also examined with fluorodeoxyglucose. PET studies of ICMRglc revealed significantly decreased global values in the patients receiving disulfiram compared with those not receiving disulfiram. PET studies of benzodiazepine receptor binding revealed decreased flumazenil influx and distribution volume in patients receiving disulfiram. The neuropsychological tests demonstrated no differences between the two groups of subjects. The findings suggest that disulfiram may influence the results of PET studies of glucose metabolism and benzodiazepine receptor binding.     

Alcoholism Treatment: A Ten-Year Follow-Up Study

Two hundred male and female patients, selected at random from all patients admitted to an inpatient alcoholism treatment facility in 1973-1974, were surveyed 10 years following treatment. Response rate was 80%, and a validity check was done. Of the 158 unstable responses, 61% reported complete or stable remission of their alcoholism for at least 3 years prior to the survey and 84% reported stable psychosocial status. Successful outcome was possible regardless of severity of drinking history or psychosocial status. Seventy-six percent (76%) of those still alive at follow-up reported remission; at most, 23% of the deceased were reported in remission prior to death. Involvement in Alcoholics Anonymous (AA) predicted abstinence, suggesting successful outcome for patients who undergo a treatment regimen, which bridges patients into AA involvement. Of those respondents who continued to sponsor other AA members throughout the follow-up period, 91% were in remission at the time of survey.     

Fulminant hepatitis and fatal toxic epidermal necrolysis (Lyell disease) coincident with clarithromycin administration in an alcoholic patient receiving disulfiram therapy

Disulfiram is widely used in the treatment of chronic alcoholism. Adverse drug reactions with fatal outcome following disulfiram therapy are infrequent, and hepatic failure accounts for most of them. Since disulfiram is a cytochrome P450 (CYP450) enzyme system inhibitor, numerous interactions with several drugs metabolized in the liver have been reported. Like disulfiram, clarithromycin inhibits a CYP450 isoenzyme, but, despite its widespread use for the treatment of respiratory tract infections, no interactions with disulfiram have been described as yet. We report a case of fatal toxic epidermal necrolysis (Lyell disease) and fulminant hepatitis shortly after starting treatment with clarithromycin in a patient who was receiving disulfiram. This is the first case of such a severe dermatosis in a patient receiving either disulfiram or clarithromycin therapy. The temporal relationship between drug administration and clinical symptoms in this case suggests a probable interaction between the 2 drugs.     

Disulfiram for the treatment of alcoholism. An evaluation in 128 men.

One hundred twenty-eight alcoholic men were assigned randomly to receive either a regular dose of disulfiram (250 mg), a pharmacologically inactive dose (1 mg), or no disulfiram. There were no statistically significant differences among the three treatment groups in total abstinence, percentage of drinking days, days worked, family stability (living with same relative), or percent of scheduled appointments kept. However, 21% of those who received the regular dose of disulfiram and 25% who received the pharmacologically inactive dose remained abstinent, whereas only 12% of those who received no disulfiram did so. These results indicate that disulfiram may be of limited value in the treatment of alcoholism, fear of the disulfiram-ethanol reaction is important in preventing drinking, and patients willing to take disulfiram are more likely to be abstinent if given the drug. We also found that complete abstinence correlated significantly with compliance and obtaining employment.     

Supervised disulfiram in the treatment of alcohol use disorder: a commentary

Background: This commentary discusses the systematic review “The efficacy of disulfiram for the treatment of alcohol use disorder (AUD)” by Jørgensen and colleagues (2011, Alcohol Clin Exp Res DOI: 10.1111/j.1530‐0277.2011.01523.x ). The main focus of the commentary is on long‐term effects, long‐term use, and psychotherapeutic application of supervised disulfiram. Methods: A brief qualitative overview is given of previous and recent clinical studies on disulfiram in alcoholism treatment. Results: The alcohol deterrent disulfiram is an effective pharmacological adjunct to the treatment of AUD when it is administered as supervised low‐dose disulfiram and is integrated in comprehensive biopsychosocial alcoholism therapy. However, the assumed underlying psychological effects of psychotherapeutic disulfiram application have never been properly investigated. Prospective long‐term follow‐up studies are rare and suggest that long‐term effects of disulfiram are associated with long‐term use and/or integration of the medication in cognitive behavior therapy. Conclusions: Evidence from decades of research suggests psychological effects as principal mode of action of supervised disulfiram. Future randomized controlled trials are needed that investigate psychological actions and long‐term outcomes of this alcohol deterrent.     

Techniques to Enhance Compliance with Disulfiram

Pharmacodynamic benefits of disulfiram in the treatment of alcoholism have yet to be clearly demonstrated. Nevertheless, research does suggest that disulfiram may well have positive effects on drinking if medicational compliance procedures are employed. This paper reviews research on four strategies for enhancing disulfiram compliance: implants, incentives, contracts, and patient information. Generalizations about the strategies are drawn and needs for future research are briefly addressed.     

Dermopathy of Graves' disease (pretibial myxedema): long-term outcome

Little is known about the long-term outcome of patients with thyroid dermopathy, an extrathyroidal manifestation of Graves' disease. Also, it is not known to what degree treatment promotes remission of the lesions. The present report supplies information on the natural course of mild, untreated and severe, treated thyroid dermopathy. In this study, we report on the outcomes of 178 patients seen at our institution between January 1969 and November 1995 with thyroid dermopathy who were followed up for an average of 7.9 yr. Nonpitting edema was the most prevalent form of dermopathy (43.3%), and the pretibial area was the region most commonly involved (99.4%). The majority of patients with dermopathy had ophthalmopathy (97.0%). Topical corticosteroids were the most commonly used treatment (53.9%). Patients with milder forms of dermopathy (40.4%) did not receive any therapy for dermopathy. Twenty-six percent of the patients experienced complete remission, 24.2% had moderate improvement (partial remission), and 50.0% had no or minimal improvement of their dermopathy at last follow-up. Patients who did not receive therapy experienced a significantly (P = 0.03) higher rate of complete remission (34.7%) than those who received local therapy (18.7%), although the combined complete and partial remission rates were not significantly different for the treated and untreated groups (P = 0.3). However, the treated and untreated groups were not comparable because our practice is to use therapy for more extensive and severe cases. All five cases of elephantiasis were in the treatment group and were less likely to have remission because of the severity of their skin condition. Patients receiving treatment were more likely to have dermatologic consultation and histologic diagnosis (P < 0.001). The beneficial effect of topical corticosteroid therapy on long-term remission rates remains to be determined.     

Recovery from alcoholism in cirrhotic patients: A study of 45 cases

In order to determine factors that influenced their recovery from alcoholism, 45 men who attended a liver clinic were studied, employing a detailed questionnaire. All had shown classic signs of cirrhosis, and 84 percent were in frank hepatic failure at the time of hospitalization. In general, they were married, blue-collar workers who drank, on average, for 27 years and either abstained or sharply curtailed their alcohol intake for 3.7 years (range one to 11 yrs) following which their hepatic function improved steadily.They reported that severe medical illness was a critical factor in the decision to stop drinking (87 percent) and that continued medical care was very helpful in their recovery from alcoholism (73 percent). Formal alcoholism treatment seldom was employed. Most stated that they “did it on their own.” Improvement in health, in psychologic state, in marital and social relations reinforced sobriety.The results indicate the potential impact of medical illness on the decision to stop drinking and the need to study further the factors that promote recovery from alcoholism in medical settings.     

A behavioral treatment of alcoholic methadone patients

Alcoholism is a frequent complication of methadone treatment and is one of the few behaviors found to correlate with methadone treatment failure. To eliminate drinking among severely alcoholic patients, we tested the efficacy of incorporating methadone into a behavioral contingency to reinforce disulfiram ingestion. Methadone was dispensed to alcoholic narcotic addicts contingent upon their ingesting disulfiram, and as a control patients were urged to take disulfiram but received methadone regardless of whether they took disulfiram. The results indicated that the reinforced disulfiram treatment was highly successful in controlling alcoholism. In addition, nonstatistically significant trends suggested that the reinforced disulfiram treatment resulted in a superior adjustment, as reflected in arrest rate, unemployment, and illicit drug use. There appeared to be no significant physiologic or behavioral adverse effects.     

Family History of Alcoholism in Women with Generalized Anxiety Disorder Who Have Premenstrual Syndrome: Patient Reports of Premenstrual Alcohol Consumption and Symptoms of Anxiety

This study sought to determine whether family history of alcoholism is related to patient reports of premenstrual alcohol consumption and whether family history of alcoholism is related to severity of anxiety-related symptoms, in women who suffer simultaneously from both premenstrual syndrome and generalized anxiety disorder. Fifty-four women with generalized anxiety disorder and prospectively demonstrated premenstrual syndrome were questioned about family history of alcoholism and alcohol consumption patterns across the menstrual cycle. Seventy-six percent of the sample reported having an alcoholic first- or second-degree relative. Furthermore, 74% of those women having a paternal-side family history of alcoholism, but only 22% of those without such a family history, reported increased alcohol consumption premenstrually. Forty-one of these women were assessed by means of psychiatric rating scales during both the premenstrual and follicular phases of the menstrual cycle. During the premenstrual, but not the follicular, phase of the menstrual cycle, women with a paternal-side family history of alcoholism experienced more severe anxiety-related somatic, but not psychic, symptoms of anxiety, than those without such a family history. These findings suggest that family history of alcoholism may be related to premenstrual alcohol consumption patterns and to the severity of premenstrually experienced somatic symptoms of anxiety in women with premenstrual syndrome, and that these women may be self-medicating with alcohol.     

Life-Table Analysis of Abstinence in a Study Evaluating the Efficacy of Disulfiram

Data from a study evaluating the efficacy of disulfiram for the treatment of alcoholism were analyzed by life-table methods. Previous analysis by more commonly used statistical tests showed a trend favoring disulfiram treatment, but the results were not statistically significant. Life-table methods are the appropriate techniques for analyzing longitudinal studies because they evaluate response to treatment over time rather than at one point in time. Analysis of our data using these methods revealed that disulfiram, combined with medical care and counseling, was superior to medical care and counseling alone in 128 men followed for 1 yr. This report demonstrates: (A) the advantage of life-table methods for evaluating treatment outcome data in alcoholism studies; and (B) the importance of disulfiram treatment in alcoholic patients similar to those we studied.     

Chemical Monitoring of Disulfiram Compliance: A Study of Alcoholic Outpatients

Poor compliance with disulfiram (Antabuse) therapy may reduce its efficacy in the treatment of alcoholism. This study was designed to examine two questions: (a) Could use of a chemical test for disulfiram ingestion be used clinically to improve disulfiram compliance and if so, (b) could improved disulfiram compliance contribute to improved compliance with other aspects of treatment? The results suggest that disulfiram compliance rates can be increased by clinical use of chemical monitoring data; however in this sample increased compliance with disulfiram did not correlate with improvements in other aspects of treatment compliance.     

Wegener granulomatosis: an analysis of 158 patients.

OBJECTIVE: To prospectively study the clinical features, pathophysiology, treatment and prognosis of Wegener granulomatosis. DESIGN: Of the 180 patients with Wegener granulomatosis referred to the National Institute of Allergy and Infectious Diseases during the past 24 years, 158 have been followed for 6 months to 24 years (a total of 1229 patient-years). MEASUREMENTS: Characteristics of clinical presentation, surgical pathology, course of illness, laboratory and radiographic findings, and the results of medical and surgical treatment have been recorded in a computer-based information retrieval system. SETTING: The Warren Magnuson Clinical Center of the National Institutes of Health. MAIN RESULTS: Men and women were equally represented; 97% of patients were white, and 85% were more than 19 years of age. The mean period of follow-up was 8 years. One hundred and thirty-three patients (84%) received "standard" therapy with daily low-dose cyclophosphamide and glucocorticoids. Eight (5.0%) received only low-dose cyclophosphamide. Six (4.0%) never received cyclophosphamide and were treated with other cytotoxic agents and glucocorticoids. Ten patients (6.0%) were treated with only glucocorticoids. Ninety-one percent of patients experienced marked improvement, and 75% achieved complete remission. Fifty percent of remissions were associated with one or more relapses. Of 99 patients followed for greater than 5 years, 44% had remissions of greater than 5 years duration. Thirteen percent of patients died of Wegener granulomatosis, treatment-related causes, or both. Almost all patients had serious morbidity from irreversible features of their disease (86%) or side effects of treatment (42%). CONCLUSIONS: The course of Wegener granulomatosis has been dramatically improved by daily treatment with cyclophosphamide and glucocorticoids. Nonetheless, disease- and treatment-related morbidity is often profound. Alternative forms of therapy have not yet achieved the high rates of remission induction and successful maintenance that have been reported with daily cyclophosphamide treatment. Despite continued therapeutic success with cyclophosphamide, our long-term follow-up of patients with Wegener granulomatosis has led to increasing concerns about toxicity resulting from prolonged cyclophosphamide therapy and has encouraged investigation of other therapeutic regimens.     

Psychiatric management of the hepatitis C patient

Opinion statement Patients with hepatitis C virus (HCV) infection have a higher prevalence of psychiatric illness compared with the general US population, and the prevalence of HCV infection in patients with severe mental illness ranges between 8% and 19%, which is four to nine times that of the general US population (1.8%). Given the association between HCV infection and psychiatric illness, gastroenterologists are on the front line of identifying comorbid psychiatric and substance use disorders and conducting a psychosocial pretreatment risk-benefit assessment for HCV infection. The use of interferon-α (IFN)-based therapies in combination with ribavirin (RBV) to eradicate HCV has been associated with frequent neuropsychiatric adverse effects (eg, affective, anxiety, cognitive, and psychotic symptoms) that compromise the management of both HCV patients with and those without a preexisting history of psychiatric illness. Consequently, gastroenterologists have been reluctant to engage patients with HCV and comorbid psychiatric illness in antiviral treatment due to concerns about exacerbating or precipitating neuropsychiatric symptoms. Despite the clinical challenge that HCV treatment of patients with comorbid HCV and psychiatric illness presents, recent research indicates that HCV treatments can be safely administered to patients with psychiatric illness provided that there is a comprehensive pretreatment assessment, a risk-benefit analysis, and ongoing follow-up of neuropsychiatric symptoms during antiviral therapy. The process of pretreatment assessment involves screening patients for psychiatric and substance use disorders, educating patients about the treatment process, and addressing available psychosocial support. Most psychotropic medications (antidepressants, mood stabilizers, antipsychotics, and neuroleptics) are thought to be safe to use in the management of patients with HCV and psychiatric illness and for the management of IFN- and RBV-induced neuropsychiatric adverse effects. Nonetheless, the prophylactic use of psychotropic medications to prevent IFN- and RBV-induced neuropsychiatric adverse effects remains a controversial topic. The use of IFN and RBV in patients with HCV and severe mental illness can be done safely with expert psychiatric follow-up. In this review, we discuss the process of pretreatment assessment of patients with HCV and psychiatric illness and specifically address IFN- and RBV-induced depression in patients receiving HCV treatment.     

The Effects of Major Depression on Alcoholism

Some patients come into treatment with clear cases of both major depression (MDD) and alcoholism. Although assumptions are often made about the relationships of these two conditions, little empirical information exists on the effects of changes in MDD on the course of alcoholism in patients presenting at psychiatric facilities. The authors used survival analysis with time-dependent covariates to investigate the effects of remissions and relapses of MDD on the 5-year course of alcoholism in 127 dual diagnosis patients. Changes in the status of MDD bad strong, significant effects on the course of alcoholism. Improvement in MDD status increased the chances of remission in alcoholism and reduced the chances of alcoholism relapse. The status of MDD appears to have an effect on the course of alcoholism in patients with severe affective disorders.     

Combined Efficacy of Acamprosate and Disulfiram in the Treatment of Alcoholism: A Controlled Study

This study presents the results of a multicenter investigation of the efficacy of acamprosate in the treatment of patients with chronic or episodic alcohol dependence. One hundred eighteen patients were randomly assigned to either placebo or acamprosate, and both groups were stratified for concomitant voluntary use of disulfiram. Treatment lasted for 380 days, with an additional 360-day follow-up period. The primary efficacy parameters evaluated were: relapse rate and cumulative abstinence duration (CAD). Results were analyzed according to Intention-To-Treat principles using χ², t , and multiple regression analyses where appropriate. After 30 days on study medication, 40 of 55 (73%) acamprosate-treated patients were abstinent, compared with 26 of 55 (43%) placebo-treated patients ( p = 0.019). The treatment advantage remained throughout the study medication period and was statistically significant until day 270 ( p = 0.028). Twenty-seven percent of patients on acamprosate and 53% of patients on placebo had a first drink within the first 30 days of the study. The mean CAD was 137 days (40% abstinent days) for the patients treated with acamprosate and 75 days (21% abstinent days) for the placebo group ( p = 0.013). No adverse interaction between acamprosate and disulfiram occurred, and the subgroup who received both medications had a better outcome on CAD than the those on only one or no medication. Acamprosate was well tolerated. Diarrhea was the only significant treatment-induced effect. It was concluded that acamprosate was a useful and safe pharmacotherapy in the long-term treatment of alcoholism. Concomitant administration of disulfiram improved the effectiveness of acamprosate.     

Substitution of methotrexate for cyclophosphamide in Wegener granulomatosis: a 12-year single-practice experience

We conducted a retrospective review to assess outcomes of therapy in patients with newly diagnosed Wegener granulomatosis (WG) using methotrexate (MTX) for mild to moderate disease and short-term treatment with cyclophosphamide (CYC) followed by MTX for severe disease. Patients with WG were included if their initial plan of therapy and subsequent care were directly supervised by the Cleveland Clinic Center for Vasculitis Care and Research. Severe disease (immediately life-threatening or involving critical organs) was initially treated with CYC and glucocorticoids. Mild to moderate disease was initially treated with MTX and glucocorticoids if serum creatinine was less than 2 mg/dL. Following initial improvement of severe disease, treatment was changed to MTX if serum creatinine was originally less than 2 mg/dL or had diminished to less than 2 mg/dL. Disease activity was determined at each visit and later converted to a Birmingham Vasculitis Activity Score, as modified for Wegener granulomatosis (BVAS/WG). Laboratory monitoring of disease and treatment toxicity was initially weekly and never less than monthly.Eighty-two (32%) of 253 patients with WG referred to the Center for Vasculitis Care and Research met eligibility criteria. Ineligible patients did not have new-onset disease or were not able to be followed principally in our center. Seventy percent of patients (57/82) initially had severe disease and received a short course of CYC for remission induction. In over half of these patients, illness was judged to be severe because of pulmonary hemorrhage; rapidly progressive glomerulonephritis, including need for dialysis; or neurologic abnormalities.All patients improved: remission was achieved in 50% (41/82) of patients within 6 months and in 72% (59/82) within 12 months. Sustained remission (BVAS/WG = 0 for at least 6 consecutive months) was ultimately achieved in 78% (64/82) of patients. Among the 75 (91%) patients who achieved remission of any duration, 45% relapsed within 1 year and 66% relapsed within 2 years following remission. Eighty-two percent of relapsed patients achieved subsequent remissions after additional treatment. About three-quarters of relapses were mild and promptly responded to treatment.Seventeen percent of patients developed serious infections. CYC-associated cystitis or bladder cancer did not occur in any patients. At least 1 form of permanent morbidity from WG alone was noted in 74.0% of patients. Three patients (3.7%) died over a median follow-up period of 4.5 years; no deaths were due to active disease.Although treatment was primarily directed toward achieving clinical improvement and not calculated to achieve marked lymphopenia, patients in whom treatment produced lymphocyte counts of 1000/mm was associated with a hazard ratio for relapse of 3.0, although the latter difference was not statistically significant.In patients with WG, a strategy that limits or avoids CYC therapy produced a frequency of remission comparable to that achieved with conventional CYC protocols, excellent survival, and avoidance of long-term CYC toxicity. However, relapses were common and incremental permanent morbidity occurred in most patients. While not a goal of therapy, when treatment produced marked lymphopenia, prolonged remissions were more likely.     

Candidates for liver transplantation with alcoholic liver disease: Psychosocial aspects

In Europe, 30% to 50% of liver transplantations are currently due to alcoholic liver disease(ALD). In the United States, this percentage is 17.2%. Post-transplantsurvival and other predictors of clinical course do not differ significantly from those in other types of transplanted patients, as long as there is no relapse of drinking. However, 20%-25% of these patients lapse or relapse to heavy drinking post-operatively, which has been associated with an increased risk of liver damage and mortality. It is therefore crucial to design specific selection and follow-up strategies aimed at this particular type of patient. Several good and poor prognosis factors that could help to predict a relapse have been suggested, among them the duration of abstinence, social support, a family history of alcoholism, abuse diagnosis versus alcohol dependence, non-acceptance of diagnosis related to alcohol use, presence of severe mental illness, nonadherence in a broad sense, number of years of alcoholism, and daily quantity of alcohol consumption. In this article, we discuss these and other, more controversial factors in selecting ALD patients for liver transplantation. Abstinence should be the main goal after transplantation in an ALD patient. In this article, we review the several definitions of post-transplant relapse, its monitoring and the psychopharmacological and psychotherapeutic treatment.