Buspirone treatment of anxious alcoholics. A placebo-controlled trial.

BACKGROUND: Symptoms of anxiety are common in alcoholics and may contribute to relapse following initiation of abstinence. Buspirone hydrochloride, a serotonin1A partial agonist, has a pharmacologic profile that may be particularly suited to the treatment of anxious alcoholics. METHODS: We conducted a randomized, 12-week, placebo-controlled trial of buspirone in 61 anxious alcoholics, all of whom also received weekly relapse prevention psychotherapy. Outcomes were measured at the end of treatment and at a 6-month follow-up evaluation. RESULTS: Buspirone therapy was associated with greater retention in the 12-week treatment trial, reduced anxiety, a slower return to heavy alcohol consumption, and fewer drinking days during the follow-up period. CONCLUSIONS: Buspirone appears to have a useful role in the treatment of anxious alcoholics. Further research is needed to clarify which patient characteristics and concomitant treatments result in optimal response to buspirone therapy.

Placebo-controlled trial of fluoxetine as an adjunct to relapse prevention in alcoholics.

OBJECTIVE: The authors tested the hypothesis that fluoxetine, when used in combination with relapse prevention psychotherapy, directly reduces relapse frequency and severity for alcoholics. METHOD: The authors conducted a randomized, placebo-controlled trial of fluoxetine (up to a maximum of 60 mg/day) for 12 weeks in combination with weekly psychotherapy for 101 alcohol-dependent subjects who were not selected on the basis of comorbid major depression. Outcomes were measured at the end of treatment and 6 months after treatment. RESULTS: Placebo-treated subjects were more complaint with the medication regimen and remained in the study longer than fluoxetine-treated subjects. There was significantly less alcohol consumption in both groups during treatment than before treatment. These effects persisted during the posttreatment period. Although fluoxetine treatment had no significant effects on alcohol consumption, it reduced Hamilton Depression Rating Scale scores more than placebo treatment among subjects with current major depression. CONCLUSIONS: Fluoxetine at a dose of 60 mg/day is probably not of use for relapse prevention in alcoholics with mild to moderate alcohol dependence and no comorbid depression. In alcoholics with major depression, the drug may reduce depressive symptoms. Subsequent studies with fluoxetine should probably focus on more severely alcohol-dependent subjects or those with comorbid depression.

Truth or consequences: the validity of self-report data in health services research on addictions.

This paper examines factors that influence the veracity of verbal self-report data in health services research, using a cognitive social-psychological model of the data-gathering process as an organizing framework. It begins by briefly summarizing the consequences that can result from measurement error. Next, a cognitive social-psychological model of the question-answering process is presented. Common assumptions regarding the utility of specific assessment methods are evaluated with particular emphasis on the strengths and weaknesses of alternative data sources. The framework is then applied specifically to understanding the factors that may affect self-report measures in health services research relating to alcohol and other substance use. Overall, self-report procedures can provide useful estimates of consumption in clinical settings when conditions are designed to maximize response accuracy.

The influence of alcohol expectancy priming and mood manipulation on subsequent alcohol consumption.

Studies showing that verbal priming can implicitly affect alcohol consumption have been used to support cognitive models of expectancies. However, because expectancy words reflect affective states as well as drinking outcomes, mediation through an affective pathway remains theoretically plausible (i.e., such words inadvertently may affect mood, which in turn influences drinking). The primary pathway was identified (and expectancy theory was tested) by comparing memory priming (using alcohol expectancy or neutral words) with mood induction (using positive or neutral music); an unrelated experiment paradigm allowed the priming manipulation to implicitly affect drinking. Men in the alcohol priming group drank significantly more than men in each of the other conditions, and, consistent with theory, men with histories of heavier drinking drank the most when primed with alcohol expectancies, indicating that expectancies can function as automatic memory processes.

Estimating measurement error in alcohol dependence symptomatology: findings from a multisite study.

Inter-rater test-retest reliability of alcohol diagnoses and symptom ratings, made by means of a modified version of the Structured Clinical Interview for DSM-III-R (SCID), were evaluated in the context of a multisite clinical trial of alcoholism treatment. Reliability coefficients for the subject's 'worst period' and the 'current period' were compared. The results show that with proper training, reliable diagnostic classification can be achieved across multiple sites. Symptom reliabilities for the current period were higher than the worst period. Respondents with higher discrepancies between test and retest tended to drink more on each drinking occasion, reported more medical detoxifications, changed residence more often, had lower occupational status and were rated by the interviewer as less attentive, motivated and intelligent. Methods to monitor and improve the reliability of diagnostic interviews in addiction research, particularly in multisite studies, are discussed in relation to the findings.

Measurement of drinking behavior using the Form 90 family of instruments.

Although drinking behavior is clearly a central dependent variable in alcoholism treatment research, the field has reached no consensus on measurement methodology for alcohol consumption. At least four methods for quantifying consumption have been commonly used in outcome studies: quantity-frequency questions, average consumption grids, timeline follow-back and self-monitoring. The Form 90 family of structured interviews was developed by collaboration among the Project MATCH investigators, combining the strengths of prior assessment methodologies. The development, structure, supporting software and training approaches for the Form 90 instruments are described.

Reliability enhancement and estimation in multisite clinical trials.

Clinical trials, particularly those in addictions research, often rely on self-report data for primary dependent variables, and it is imperative to evaluate and to minimize both random and systematic error. This article describes methods for enhancing and assessing reliability of measurement in multisite clinical research. It begins with an overview of the two major approaches to evaluating the reliability of psychiatric diagnosis and verbal self-reports. A model of the interview process is then described, and the major sources of inconsistency that arise in the data collection process are identified. Based on the model, staff selection criteria, training techniques and quality assurance procedures are recommended for enhancing the reliability of interview assessments, and a research design appropriate for evaluating reliability in multisite clinical investigations is proposed.

Ensuring balanced distribution of prognostic factors in treatment outcome research.

In comparative or matching research involving two or more treatments, the equivalence of the patient groups is of critical importance. In the past, equivalence has either been imposed by matching or balancing, or has been assured statistically by randomization. Matching and balancing, while useful in many contexts, nonetheless have important limitations, as does simple randomization. In recent years, a new tool has been developed that represents a compromise between balancing and randomization. This method, urn randomization, gives clinical investigators new options for improving the credibility of studies at a relatively modest cost. Urn randomization is randomization that is systematically based in favor of balancing. It can be used with several covariates, both marginally and jointly, producing optimal multivariate equivalence of treatment groups for large sample sizes. It preserves randomization as the primary basis for assignment to treatment and is less susceptible to experimenter bias or manipulation of the allocation process by staff than is balancing. Disadvantages include the fact that it is more difficult to implement, and that it violates the simple probability model of simple randomization. A number of research studies on addictions, including client-treatment matching trials, have used urn randomization. A summary of the mechanics of urn randomization is presented, and guidelines for its use in treatment studies are discussed.

Developments in alcoholism treatment research: patient-treatment matching.

This article describes patient-treatment matching, a recent advance in alcoholism treatment research. A general description of the concept is presented and the challenges patient-treatment matching poses for investigators and for treatment providers are described. Project MATCH, a multisite clinical trial designed to test the matching hypothesis is used to illustrate approaches to addressing the research challenge. Two additional avenues of promising patient-treatment matching research, one relating to patient characteristics and the other to pharmacological treatments, are also summarized. The article concludes with a brief prescription for individual providers to implement and test treatment matching strategies in their own clinical practice.

Comorbid psychiatric diagnosis predicts three-year outcomes in alcoholics: a posttreatment natural history study.

OBJECTIVE: To examine the impact of three common comorbid disorders on a variety of outcomes 3 years after inpatient alcoholism treatment. METHOD: Using a prospective cohort design, we examined the frequency and intensity of drinking, the severity of alcohol-related symptoms, global alcohol-related outcome and severity of psychiatric symptoms in a group of 225 (74% male) alcoholics. At the index admission, patients were categorized as to the lifetime presence of major depression, antisocial personality disorder (ASP) and drug abuse/dependence. Multiple linear regression was used hierarchically to step in blocks of predictors in a logical sequence: (1) gender and age; (2) number of comorbid psychiatric diagnoses and the presence or absence of the three individual comorbid psychiatric disorders; and (3) the interaction between gender and each of the three diagnostic groups. RESULTS: Men showed greater intensity of drinking, more alcohol-related symptoms and poorer global alcohol-related outcome. Younger patients also showed more alcohol-related symptoms. Although the number of comorbid diagnoses was correlated with both the intensity of drinking and the severity of psychopathology, each of the specific comorbid diagnoses accounted for unique variance in outcome. Comorbid drug abuse/dependence was associated with more drinking days and more alcohol-related symptoms. In contrast, the presence of comorbid major depression was associated with lower intensity of drinking. Finally, ASP was associated with poorer global alcohol-related outcome. CONCLUSIONS: Outcomes 3 years after alcoholism treatment are related to the presence of specific lifetime comorbid psychiatric diagnoses. Since such disorders may positively influence the course of alcoholism, trials of clinical interventions that target these disorders are warranted.

Levels and patterns of alcohol consumption using timeline follow-back, daily diaries and real-time "electronic interviews".

OBJECTIVE: This study was designed to compare the Timeline Follow-Back (TLFB) to daily and real-time assessments of drinking. Our purpose was to evaluate overall correspondence and day-to-day agreement between these two methods among both problem and moderate drinkers. METHOD: In Study 1, problem drinkers (n = 20) reported their alcohol consumption daily during 28 days of brief treatment. In Study 2, moderate drinkers (n = 48), recruited from the community, used a palm-top computer to record their drinking for 30 days. In both studies participants completed the TLFB covering the recording period. RESULTS: Participants in Study 1 reported fewer drinking days, fewer drinks per drinking day and fewer total drinks per day on the TLFB, and those in Study 2 reported fewer drinks per drinking day, fewer ounces per drinking day, fewer total drinks per day and fewer total ounces per day. The magnitude of the difference, however, was modest. There was considerable between-person variation in day-to-day correspondence of TLFB and the daily and real-time reports. Neither person characteristics (gender, education and income) nor the distributional characteristics of drinking (including average consumption, variation) predicted concordance between TLFB and real-time reports. CONCLUSIONS: The Timeline Follow-Back method captured overall levels of drinking quite well compared to a 28-day daily diary and a 30-day electronic interview. Vast individual differences in day-to-day correspondence suggest that the TLFB may be less useful for detecting patterns of consumption.

"Getting by (or getting high) with a little help from my friends": an examination of adult alcoholics' friendships.

OBJECTIVE: Researchers have devoted much attention to the influence of social support on positive health outcomes, including efficacy of alcoholism treatment. Yet relatively little research has examined the structure (e.g., quantity or frequency of interactions) and quality (e.g., subjective appraisals of value or adequacy) of alcoholics' relationships. In addition, few studies have explored adult alcoholics' friendships, despite research suggesting that friendships influence treatment outcomes. The current study examined friendship characteristics of Project MATCH participants. METHOD: Participants (1,183 men, 380 women) described the structure and quality of their friendships at baseline and posttreatment. Friendships with drinkers and nondrinkers were examined in relation to baseline and follow-up drinking levels, as well as participant gender, age and parental history of alcohol problems. RESULTS: Significant changes were found in all aspects of friendships with both drinkers and nondrinkers from baseline to the 6-month posttreatment interview. For example, although approximately half of alcoholics friendships were with drinkers at baseline, that proportion decreased following treatment, whereas the proportion of friendships with nondrinkers increased. There was support for the hypothesis that changes in both friendship quality and structure would predict follow-up drinking levels. CONCLUSIONS: This study offers persuasive evidence for the importance of quality and, especially, structure of friendships to adult alcoholics' drinking behavior. Results also suggest differences in friendships depending on gender and across the lifespan. Such individual differences may have implications for prevention and treatment.

Self-reports of physical, sexual and emotional abuse in an alcoholism treatment sample.

OBJECTIVE: There is a growing appreciation that emotional, physical and sexual abuse events are frequently part of the life histories of individuals in treatment for alcohol disorders. The present study examines reports of lifetime abuse in a clinical trial for treatment of alcohol dependency. METHOD: Data were obtained from baseline assessments conducted with participants (N = 1,726; 1,307 men) entering Project MATCH, a multisite clinical trial conducted at nine geographically dispersed research sites. Differences on a broad range of participant characteristics were examined by gender and by reported abuse type. RESULTS: More than half (59%) of the participants reported lifetime abuse. Women were more likely (77%) to report abuse than were men (54%). A lower proportion of men than women (6% vs 31%) reported experiencing both physical and sexual abuse. Gender differences were found on the majority of psychosocial measures. Comparisons of the psychosocial measures by abuse type generally indicated that participants without abuse histories had better functioning than did participants reporting abuse. CONCLUSIONS: The high frequency of lifetime abuse in this geographically dispersed sample underscores the necessity for including assessment of emotional, physical and sexual abuse with alcoholism treatment seeking populations. Participants reporting such events may require other treatment in addition to that for alcohol dependency.

Telescoping of landmark events associated with drinking: a gender comparison.

OBJECTIVE: The literature suggests that women exhibit "telescoped" development of (i.e., faster progression to) alcoholism, with fewer years drinking than men. The purpose of this study was to use data gathered in the course of a large clinical trial to further examine this issue. METHOD: Subjects in this retrospective study were from a pool of 1,307 men and 419 women enrolled in Project MATCH, a multisite alcohol treatment matching study. MATCH subjects were recruited from both outpatient and aftercare settings over a 2-year period. Age-of-onset for landmark events in the development of alcoholism were determined from self-report and clinical interviews given at baseline entry into the study. Gender differences in age-of-onset variables were assessed within both outpatient and aftercare settings. Gender differences in progression times between successive landmarks were also examined. Differences were tested with both multivariate and univariate ANOVA techniques. RESULTS: Women generally began getting drunk regularly at a later average age than men (26.6 versus 22.7 years, p< or =.001), began experiencing their first drinking problems at a later average age than men (27.5 versus 25.0 years, p< or =.001) and exhibited loss of control over their drinking at a later average age than men (29.8 versus 27.2 years, p< or =.001). However, these gender differences were most pronounced for older individuals and attenuated for younger subjects. Women also progressed faster than men, on average, between first getting drunk regularly and first encountering drinking problems (0.9 versus 2.3 years, p< or =.001) and between first loss of drinking control and onset of worst drinking problems (5.5 versus 7.8 years, p< or =.001). Women also exhibited shorter average progression times between first getting drunk regularly and first seeking treatment (11.6 versus 15.8 years, p< or =.001), although this effect was negligible for younger subjects. CONCLUSIONS: Telescoping is a relatively robust phenomenon in treatment-seeking alcoholics and indicates that women are more likely to progress faster through the landmark events in the development of alcoholism than are men.

Self-reports by alcohol and drug abuse inpatients: factors affecting reliability and validity.

The reliability and validity of self-report data regarding substance abuse has often been questioned. To determine how best to enhance the veracity of self-report, three factors which might affect self-report veracity were examined: alcohol status at time of interview; level of cognitive functioning; and method of self-report data collection. Subjects were 234 admissions to an inpatient substance abuse treatment unit. Self-report data were collected via both personal interview on the day of admission and and questionnaire within the first week of stay. Self-reports concerned use of alcohol, cocaine, and marijuana in the days preceding admission. Test-retest reliability for the questionnaire data produced reliability coefficients of 0.88, 0.91, and 0.88, for alcohol, cocaine, and marijuana, respectively. Variation in inter-test interval had virtually no effect upon reliability coefficients. Interview data were compared to toxicologic analyses of blood and urine samples collected on admission. Overall, this comparison showed self-reports to be valid, with a 97% agreement between verbal report and laboratory data for alcohol, 93% for cocaine, and 84% for marijuana. The comparison of interview data with questionnaire responses also showed self-reports to be valid: 90% agreement for alcohol, 93% for cocaine, and 81% for marijuana. Level of cognitive function did not influence the validity of self-reports for any of the three substances. Recent consumption of alcohol also had no statistically significant effect on the validity of self-reported marijuana use, regardless of the operational form of validity tested. However, BAC-negative subjects produced a significantly greater validity coefficient for self-reported cocaine use (kappa = 0.87) than did BAC-positive patients (kappa = 0.43), when interview data were compared with toxicologic measures. A similar finding was not uncovered when interview and questionnaire data were compared. An interaction between admission alcohol status and cognitive function was uncovered for cocaine self-reports when interview data was compared with toxicologic measures. The rate of agreement for alcohol-negative subjects is quite high for both cognitively impaired and unimpaired subjects (M = 93% and M = 94%, respectively) as well as for alcohol-positive, cognitively unimpaired subjects (M = 94%), but not for alcohol-positive, cognitively impaired subjects (M = 67%). Results are discussed in terms of threats to the validity of self-report and strategies for the optimization of response accuracy.

Assessment of medication compliance in alcoholics through UV light detection of a riboflavin tracer.

Compliance with the medication regimen in treatment trials for alcoholism appears to be a key determinant of treatment outcome. However, there is no consensus as to the best method to assess medication compliance. This study examines the feasibility of using ultraviolet light detection of a urinary riboflavin tracer to determine compliance with medication therapy. Six sets of urine specimens (with n ranging from 15 to 38) were rated independently by two judges. Test-retest reliability was high: 90 and 95% agreement for two judges. Inter-rater reliability ranged from 73 to 95% agreement between judges (mean = 88%), with correspondence kappa values ranging from 0.46 to 0.85 (mean = 0.69). Diaries, capsule counts, and spectrofluorimetric data were used to validate judges' ratings in four trials, including one in which subjects were alcohol-dependent participants in one of three pharmacotherapy trials. Rating accuracy was influenced by dosage, time interval between ingestion and urine collection, and previous dosing. Overall, ratings tended to be accurate, with incorrect judgments limited to specimens with low concentrations of urinary riboflavin. The results indicate that ultraviolet light detection of urinary riboflavin is a useful method for the assessment of patient compliance with medication regimens, including compliance of patients assigned to receive placebo in clinical trials of medications for alcoholism treatment.

Compliance with treatment and follow-up protocols in project MATCH: predictors and relationship to outcome.

Treatment and follow-up session attendance data from Project MATCH, a multisite clinical trial investigating patient-treatment matching, were analyzed to study compliance. High rates of compliance to both therapy and research protocols were achieved, enhancing treatment integrity and data quality. Strong baseline predictors of compliance did not emerge, and the small relationships found were consistent with reports from previous studies. Attendance at therapy sessions was moderately correlated with research follow-up participation. Treatment compliance predicted drinking outcome, underscoring the importance of retaining patients in treatment. Future studies should examine the associations between compliance and structural features of the treatment environment, treatment delivery, and context-features that are often under the control of the clinician/investigator.