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.     

Functioning of alcohol use disorder criteria among men and women with arrests for driving under the influence of alcohol

Background: Many states require screening of individuals arrested for driving under the influence (DUI) of alcohol to determine recidivism risk and the need for treatment based on severity of alcohol problems. Several screening instruments use DSM‐IV criteria for alcohol abuse and dependence to assess alcohol problems in this population, but whether they adequately measure alcohol problems in individuals with DUIs has not been examined. In addition, gender differences in DUI samples suggest that female offenders have more severe alcohol problems than male offenders. The current study examines differences in alcohol criteria functioning by DUI history and gender using an item response theory (IRT) approach. Methods: Data from diagnostic interviews with 8,605 participants in the Collaborative Study on the Genetics of Alcoholism, including 1,655 who ever reported a DUI arrest (20% women), were used to examine differences in alcohol criteria functioning between men and women with and without DUIs. The factor underlying item response was conceptualized as unidimensional, representing alcohol problem severity. Results: Social/interpersonal problems, larger/longer, and inability/persistent desire to quit displayed greater discrimination of IRT‐defined alcohol problem severity among individuals with DUIs than those without. Irrespective of DUI status, women had a higher threshold than men for time spent drinking or recovering. Women without DUIs had a higher threshold than similar men for social/interpersonal problems. Taken as a whole, the criteria yielded similar amounts of information in all groups. Conclusions: DSM‐IV criteria for alcohol abuse and dependence adequately detect alcohol problem severity in individuals with DUIs, and some are better at detecting severity in this particularly high‐risk group than in individuals without DUIs. However, the criteria as a whole are equally effective in measuring alcohol problem severity among individuals with and without DUIs and may be used with confidence in screening DUI offenders.     

Predictors of 16-year mortality among individuals initiating help-seeking for an alcoholic use disorder

BACKGROUND AND METHODS: We examined rates and predictors of mortality in individuals (47% women) who had just initiated help-seeking for their alcohol use disorders (AUDs) at the start of the study (n=628) and were followed for 16 years. RESULTS: For both women and men, the observed-to-expected mortality ratio (1.4) was lower than rates found in samples of treated individuals with AUDs, suggesting that those initiating help-seeking careers have better chances of long-term survival. Of the individuals for whom cause of death was known, 68% died of alcohol-related causes. Men were more likely to die than were women. When gender was controlled, individuals who were older and unmarried and had more alcohol dependence symptoms at baseline were more likely to die over the 16-year period. When these baseline characteristics were controlled, better drinking outcomes at 1 year were associated with a lower likelihood of subsequent death. The combination of a shorter duration of inpatient/residential care and better drinking outcomes at 1 year was related to a lower probability of death, as was the combination of a longer duration of outpatient care or Alcoholics Anonymous attendance and better drinking outcomes at 1 year. CONCLUSIONS: Efforts should be made to help providers identify individuals who are not responding positively to inpatient or residential treatment and intervene to motivate participation in continuing outpatient care and community 12-step self-help groups to reduce the likelihood of a chronic and fatal AUD course.     

The effect of pre-existing alcohol use disorder on the risk of developing posttraumatic stress disorder: results from a longitudinal national representative sample

ABSTRACT

Background: There is inconsistent evidence in the literature as to whether or not Alcohol Use Disorder (AUD) is a risk factor for Post-Traumatic Stress Disorder (PTSD).

Objectives: We evaluated the risk of developing PTSD after trauma exposure in individuals with AUD. As a secondary analysis, we also tested if alcohol dependence or alcohol abuse separately increased the risk of PTSD development. We also explored the effect of AUD on exposure to various traumas.

Methods: Longitudinal data was obtained from 30,180 individuals with and without AUD from National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) waves I and II. Using propensity score methods, we matched individuals with AUD (alcohol abuse and/or dependence using DSM-IV criteria) to those without AUD at baseline on demographic, familial, and clinical factors to estimate the risk of PTSD development after trauma exposure. Data were adjusted for complex survey methods.

Results: Individuals with AUD had an increased risk of being exposed to various traumas between wave I and II (60.6% vs. 48.3% of controls). Among individuals exposed to trauma between the two waves (N = 14,107), AUD had no effect on subsequent PTSD development after matching and controlling for covariates (OR: 1.00; 95%CI: 0.72–1.39; p = .99). However, those with alcohol dependence only did have an effect on subsequent PTSD development (OR: 1.76; 95%CI: 1.05–2.95; p = .03).

Conclusion: In individuals with alcohol dependence the experience of trauma increases the risk of developing PTSD. These findings suggest that prevention methods from PTSD after trauma exposure for individuals with alcohol dependence are needed.     

Antisocial behavioral syndromes and DSM-IV alcohol use disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions

BACKGROUND: Antisocial personality disorder (ASPD), syndromal adult antisocial behavior (AABS) without conduct disorder (CD) before age 15, and CD without progression to ASPD ("CD only") are highly prevalent among adults with alcohol use disorders (AUDs). Among patients in AUD treatment, antisocial behavioral syndromes are associated with more severe AUDs and poorer treatment outcomes. Comparative data concerning associations of antisocial syndromes with clinical characteristics of AUDs and the sociodemographic and clinical correlates of these syndromes among general population adults with AUDs have not previously been available. This study examines prevalences and correlates of antisocial syndromes among adults with lifetime Diagnostic and Statistical Manual--Version IV (DSM-IV) AUDs, and describes associations of these syndromes with clinical characteristics of AUDs, in the general U.S. population. METHODS: This report is based on the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (n=43,093, response rate=81%). Respondents (n=11,843) with lifetime AUDs were classified according to whether they met criteria for ASPD, AABS, "CD only," or no antisocial syndrome. Correlates of antisocial syndromes were examined using contingency table approaches and normal theory analyses of variance. Associations of antisocial syndromes with clinical characteristics of AUDs, including number of lifetime episodes, duration of longest or only episode, and alcohol consumption during period of heaviest drinking were examined using normal theory and logistic regression. RESULTS: Sociodemographic and clinical correlates of antisocial syndromes among respondents with AUDs were consistent with results from prior studies. Antisocial syndromes were significantly associated with phenomenology of AUDs, particularly ASPD with the most severe clinical presentations. Associations with AABS were similar to but more modest than those with ASPD; those with "CD only" were weaker and less consistent. Patterns of associations between antisocial syndromes and clinical characteristics of AUDs were generally similar between men and women. CONCLUSIONS: Antisocial syndromes, particularly ASPD, appear to identify a more pernicious clinical profile of AUDs among adults in the general U.S. population.     

A Call to Action: A Systematic Review Examining the Failure to Include Females and Members of Minoritized Racial/Ethnic Groups in Clinical Trials of Pharmacological Treatments for Alcohol Use Disorder

Alcohol use disorder (AUD) presents a significant public health concern given the high prevalence estimates and numerous deleterious-associated consequences. The FDA currently has approved 3 pharmacological treatments for alcohol use disorder: acamprosate, naltrexone, and disulfiram. Previous research suggests that there may exist differences in the prevalence of and outcomes related to AUD across sex and racial/ethnic groups. Other work indicates that there may be differences in the efficacy of existing pharmacological treatments for AUD across demographic groups. The purpose of the present study was to examine the inclusion of women and members of minoritized racial/ethnic groups in published randomized clinical trials of pharmacological treatments for alcohol use disorder since 1994, in accordance with the NIH Revitalization Act of 1993. PubMed was systematically searched using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The initial search located 842 articles. After exclusion of ineligible articles, 102 remained for analysis. Of those included in the review, only 11.8% reported full sex and racial/ethnic characteristics of their study participants. Of the total sample, 6 articles were specifically examining 1 racial/ethnic group, and 11 were specifically examining 1 sex. Two articles (2.2%) did not report information regarding the sex breakdown of their participants, while 47 (49.0%) did not report any information regarding the racial/ethnic breakdown of their sample. Despite guidelines set forth by NIH, only 5.9% of articles conducted subgroup analyses to examine differences in treatment outcomes by sex or race/ethnicity, and only 16.7% of articles included considerations related to cultural inclusion when discussing study limitations. These results varied by medication type. Results suggest that considerably greater efforts must be put forth by the larger scientific community regarding the inclusion, analysis, and reporting of data focused on women and non-White racial and ethnic groups.     

Predictors of a suicide attempt one year after entry into substance use disorder treatment

BACKGROUND: The present study examined the patient intake and treatment-related risk factors associated with a suicide attempt in the 30 days before a 1-year posttreatment assessment. METHODS: A national sample of 8,807 patients presenting for treatment of substance use disorders (SUDs) in the Department of Veterans Affairs healthcare system were assessed at treatment intake and follow-up. Using the MacArthur Model, the risk and protective factors for suicide attempt were identified at baseline and during treatment. RESULTS: At follow-up, 4% (314/8,807) of the patients reported a suicide attempt within the past 30 days. Baseline predictors of a suicide attempt before follow-up included elevated suicidal/psychiatric symptoms, more recent problematic alcohol use, and longer duration of cocaine use. Contact with the criminal justice system was a protective factor that reduced the likelihood of a future suicide attempt. Greater engagement in SUD treatment was also associated with a reduction in suicide risk. CONCLUSIONS: More involvement in SUD treatment reduced the likelihood of a future suicide attempt in high-risk patients. Substance use disorder treatment providers interested in reducing future suicidal behavior may want to concentrate their efforts on identifying at-risk individuals and actively engaging these patients in longer treatment episodes.     

Alcohol-induced bone marrow damage: Status before and after a 4-week period of abstinence from alcohol with or without disulfiram

Summary The investigation described in this paper has confirmed the existence of alcohol-induced bone marrow damage as a nosological entity in alcohol-dependent individuals. In our patients total abstinence from alcohol without disulfiram or similar drugs led to reversal of the pathological findings in peripheral blood and in bone marrow. In patients undergoing detoxification while taking disulfiram, on the other hand, the pathological bone marrow findings, especially erythropoiesis associated with impaired iron utilization, persisted. The metabolic pathway of disulfiram is discussed. It is probably justifiable to assume that the toxin responsible for alcohol-induced bone marrow damage is the ethanol metabolite acetaldehyde. The persistence of erythropoiesis with impaired iron utilization during abstinence from alcohol and treatment with disulfiram is also of importance in differential diagnosis from the myelodysplastic syndrome (MDS), and especially from refractory anaemia with ring sideroblasts (RARS). For this reason, where the situation is unclear, it is essential that a diagnosis of MDS be supported by specific investigations such as cell cultures, cytogenetic analyses, etc. It is the first time that the toxic, alcohol-like-effect of disulfiram on haematopoiesis is discussed.     

Threshold and optimal cut-points for alcohol use disorders among patients in the emergency department

Background: Current research suggests that Diagnostic and Statistical Manual of Mental Disorder (DSM)‐IV alcohol abuse and dependence form a unidimensional continuum in emergency department (ED) patients in 4 countries: Argentina, Mexico, Poland, and the United States. In this continuum of alcohol use disorder (AUD), there are no clear‐cut distinctions between the criteria for dependence and abuse in the severity dimension based on prior results from item response theory (IRT) analysis. Nevertheless, it is desirable to find a threshold for identifying cases for clinical practice and cut‐points of clinical utility in this continuum to distinguish between patients more or less affected by an AUD, using a scale of symptoms count. Methods: Data from 5,193 patients in 7 ED sites in the same 4 countries (3,191 current drinkers) were used to study the structure, threshold, and possible cut‐points for the diagnoses of AUD. Results: The proposed changes in the DSM‐V, dropping the abuse item “legal problems” and adding an item on “craving,” did not impact the IRT performance and unidimensionality of AUD in this sample. With a total set of 11 items (deleting “legal problems” and adding “craving” to the current set of DSM criteria), an endorsement of 2 or more criteria can be used as the threshold to define those with an AUD in clinical practice. Furthermore, we can distinguish at least 2 levels of clinical severity, 2 to 3 criteria (moderate), and 4 or more criteria (severe). Conclusions: A dimensional approach to AUD using the proposed new set of criteria for the DSM‐V can be used to propose a threshold and levels of severity. More research in different populations and countries is needed to further substantiate a threshold and cut‐points that could be used in new formulations of substance use disorders.     

Gender differences in the performance of a computerized version of the alcohol use disorders identification test in subcritically injured patients who are admitted to the emergency department

OBJECTIVE: The Alcohol Use Disorder Identification Test (AUDIT) has been recommended as a screening tool to detect patients who are appropriate candidates for brief, preventive alcohol interventions. Lower AUDIT cutoff scores have been proposed for women; however, the appropriate value remains unknown. The primary purpose of this study was to determine the optimal AUDIT cutpoint for detecting alcohol problems in subcritically injured male and female patients who are treated in the emergency department (ED). An additional purpose of the study was to determine whether computerized screening for alcohol problems is feasible in this setting. METHODS: The study was performed in the ED of a large, urban university teaching hospital. During an 8-month period, 1205 male and 722 female injured patients were screened using an interactive computerized lifestyle assessment that included the AUDIT as an embedded component. World Health Organization criteria were used to define alcohol dependence and harmful drinking. World Health Organization criteria for excessive consumption were used to define high-risk drinking. The ability of the AUDIT to classify appropriately male and female patients as having one of these three conditions was the primary outcome measure. RESULTS: Criteria for any alcohol use disorder were present in 17.5% of men and 6.8% of women. The overall accuracy of the AUDIT was good to excellent. At a specificity >0.80, sensitivity was 0.75 for men using a cutoff of 8 points and 0.84 for women using a cutoff of 5 points. Eighty-five percent of patients completed computerized screening without the need for additional help. CONCLUSIONS: Different AUDIT scoring thresholds for men and women are required to achieve comparable sensitivity and specificity when using the AUDIT to screen injured patients in the ED. Computerized AUDIT administration is feasible and may help to overcome time limitations that may compromise screening in this busy clinical environment.     

Follow-up of 180 alcoholic patients for up to 7 years after outpatient treatment: impact of alcohol deterrents on outcome

OBJECTIVE: (1) To perform a 9-year study of abstinence, lapse, and relapse in 180 chronic alcoholic patients, participants of the Outpatient Longterm Intensive Therapy for Alcoholics (OLITA); (2) To investigate the role of supervised alcohol deterrents (AD) in relapse prevention and as an adjunct for maintenance of long-term abstinence. METHOD: This prospective open treatment study evaluates the long-term course of drinking outcomes and AD use of 180 chronic alcoholics consecutively admitted from 1993 to 2002. Subsamples are compared for (1) sham-AD versus verum-AD (disulfiram/calcium carbimide), (2) coped lapses versus finally detrimental lapses versus malignant relapses, and (3) AD use for 13 to 20 versus >20 months. RESULTS: In this 9-year study, the cumulative probability of not having relapsed was 0.52, and that of not having consumed any alcohol was 0.26. Despite long-term use, disulfiram/calcium carbimide was well tolerated. Patients on sham-AD (due to contraindications to verum-AD) showed higher cumulative abstinence probability than patients on verum (S = 0.86 vs. S = 0.49, p = 0.03). Detrimental lapses and malignant relapses occurred earlier than successfully coped lapses (p < 0.001); patients with detrimental lapse and with malignant relapse had fewer days of AD intake and less subsequent days without AD than patients with coped lapse (p < 0.001). The cumulative abstinence probability was S = 0.75 for patients with long-term intake compared with S = 0.50 for patients who stopped AD between months 13 and 20 (p < 0.001). CONCLUSIONS: An abstinence rate of >50% in this 9-year study strongly supports the concept of comprehensive, long-term outpatient treatment of alcoholics. Supervised, guided intake of AD, also over extended periods, can be used as a predominantly psychologically acting ingredient of successful alcoholism therapy.     

Attention-deficit/hyperactivity disorder risk for heavy drinking and alcohol use disorder is age specific

BACKGROUND: This study was designed to assess age specificity in the risk for heavy drinking and alcohol use disorder (AUD) among adolescents and young adults with Attention-Deficit/Hyperactivity Disorder (ADHD) diagnosed in childhood. METHOD: Children diagnosed with ADHD (n=364 probands) were interviewed an average of 8 years later in the Pittsburgh ADHD Longitudinal Study, either as adolescents (11-17 years old) or as young adults (18-28 years of age). Demographically similar age-matched participants without ADHD were recruited as adolescents (n=120) or as adults (n=120) for comparison with the probands. Alcohol involvement was assessed comprehensively to include measures of heavy drinking that are standard in alcoholism research and prognostic of later alcohol-related problems. RESULTS: Results revealed age specificity in the association such that episodic heavy drinking (measured as 5+ drinks per occasion), drunkenness, DSM-IV AUD symptoms, and DSM-IV AUD were elevated among 15- to 17-year-old probands, but not among younger adolescents. Among young adults, drinking quantity and AUD were elevated among probands with antisocial personality disorder. Childhood predictors indexing antisocial behavior were also examined. CONCLUSIONS: The age- specificity of these findings helps to explain prior inconsistencies across previous studies regarding risk for alcohol-related outcomes among children with ADHD.     

Severity of acute illness is associated with baseline readiness to change in medical intensive care unit patients with unhealthy alcohol use

Background: Unhealthy alcohol use predisposes to multiple conditions that frequently result in critical illness and is present in up to one‐third of patients admitted to a medical intensive care unit (ICU). We sought to determine the baseline readiness to change in medical ICU patients with unhealthy alcohol use and hypothesized that the severity of acute illness would be independently associated with higher scores on readiness to change scales. We further sought to determine whether this effect is modified by the severity of unhealthy alcohol use. Methods: We performed a cross‐sectional observational study of current regular drinkers in 3 medical ICUs. The Alcohol Use Disorders Identification Test was used to differentiate low‐risk and unhealthy alcohol use and further categorize patients into risky alcohol use or an alcohol use disorder. The severity of a patient’s acute illness was assessed by calculating the Acute Physiologic and Chronic Health Evaluation II (APACHE II) score at the time of admission to the medical ICU. Readiness to change was assessed using standardized questionnaires. Results: Of 101 medical ICU patients who were enrolled, 65 met the criteria for unhealthy alcohol use. The association between the severity of acute illness and readiness to change depended on the instrument used. A higher severity of illness measured by APACHE II score was an independent predictor of readiness to change as assessed by the Stages of Change Readiness and Treatment Eagerness Scale (Taking Action scale; p < 0.01). When a visual analog scale was used to assess readiness to change, there was a significant association with severity of acute illness (p < 0.01) that was modified by the severity of unhealthy alcohol use (p = 0.04 for interaction term). Conclusions: Medical ICU patients represent a population where brief interventions require further study. Studies of brief intervention should account for the severity of acute illness and the severity of unhealthy alcohol use as potential effect modifiers.