Effect of tryptophan depletion on alcohol cue-induced craving in abstinent alcoholic patients.

BACKGROUND: The capacity of alcohol cues to precipitate the desire to drink may be an important determinant of relapse to alcohol use in recovering alcohol-dependent patients. This study evaluated whether attenuation of serotonin synthesis via depletion of its precursor tryptophan reduces the magnitude of cue-induced craving for alcohol in recently abstinent alcoholic individuals. METHODS: Alcohol-dependent patients (n = 16), 1 to 3 months after detoxification, who exhibited a 20% or greater increase in reported craving when presented with an alcoholic beverage, completed two additional alcohol cue-exposure test days, 1 week apart. Each cue exposure was preceded by administration of a concentrated amino acid drink that resulted in a rapid and significant decline in plasma free tryptophan (active depletion, no tryptophan supplementation) or a similar drink containing tryptophan (placebo depletion). Tests were conducted in a randomized, double-blind fashion. RESULTS: There were no significant changes in the magnitude of cue-induced craving with active tryptophan depletion compared with placebo. CONCLUSIONS: These data question the dependence of alcohol cue-induced craving in sober alcoholics on the ongoing synthesis of serotonin.

Prospective matching of alcoholic clients to cognitive-behavioral or interactional group therapy.

OBJECTIVE: In earlier work, client sociopathy and global psychopathology were effective variables for treatment matching: clients low on both sociopathy and severity of psychopathology were likely to benefit from interactional group therapy, whereas those scoring high on either of these dimensions benefited more from a coping skills intervention. The present study assessed whether outcomes improve further when clients are assigned to group treatments prospectively based on a matching strategy derived from the previous findings. METHOD: All participants (N = 250, 66% men) met criteria for alcohol dependence or abuse. About half were prospectively assigned to either cognitive-behavioral (CB) coping skills training or interactional therapy, those with higher levels of psychiatric severity or sociopathy were given CB and those who were low on both dimensions were given interactional therapy. The other half were randomly assigned to those treatments, replicating the procedure of the earlier study. Outcome data were collected at the conclusion of treatment and at 3-month intervals for 1 year following. RESULTS: Prospective matching of clients to treatment did not produce superior drinking outcomes compared to random treatment assignment. Randomly assigned clients were more likely to be abstinent at the end of treatment, but this effect disappeared at later follow-ups. Prospectively matched clients had fewer negative consequences of drinking than did those assigned randomly (unmatched). Neither sociopathy nor psychiatric severity was particularly effective for matching. CONCLUSIONS: The matching effects from our previous study were not replicated. Nevertheless, prospective matching did reduce the negative consequences of drinking, consistent with our previous results.

Reactivity to alcohol-related stimuli in the laboratory and in the field: predictors of craving in treated alcoholics.

AIMS: (1) To search for predictors of alcohol craving in treated alcoholics; (2) to evaluate the relationship between craving and drinking immediately after treatment. DESIGN: Alcoholic patients in treatment underwent cue-reactivity trails in the laboratory and then recorded craving in the field using hand-held computers. Laboratory craving was correlated with craving in the field, and moods and situations recorded in the field were correlated with contemporaneous craving ratings using a multi-level correlational design. SETTING: A VA Medical Center substance abuse treatment program provided the treatment and laboratory settings. The patients' home environment was the field setting. PARTICIPANTS: Male alcohol-dependent veterans (N = 26) treated in a VA inpatient or intensive outpatient program. INTERVENTION: Participants underwent two cue-reactivity laboratory sessions prior to discharge to measure craving. Following discharge, participants recorded drinking and cravings eight times per day for 21 consecutive days. MEASUREMENTS: Craving ratings in the laboratory and multiple recordings per day of surroundings, craving and mood state in the field. FINDINGS: Desire to drink in the laboratory accounted for 8-10% of the variance in later drinking and urges to drink recorded in the field--a modest correlation. Frequency of positive urges in the field was significantly correlated with drinking frequency. Those who reported urges in the field had greater alcohol dependence and higher trait anger and anxiety scores than non-reporters. CONCLUSIONS: Craving is related to drinking immediately following treatment, and is most likely in those who have more severe dependence and greater mood disturbance. These individuals may benefit most from interventions for coping with cravings after treatment.

Day treatment versus enhanced standard methadone services for opioid-dependent patients: a comparison of clinical efficacy and cost.

OBJECTIVE: This study examined the differential efficacy and relative costs of two intensities of adjunctive psychosocial services--a day treatment program and enhanced standard care--for the treatment of opioid-dependent patients maintained on methadone hydrochloride. METHOD: A 12-week randomized clinical trial with 6-month follow-up was conducted in a community-based methadone maintenance program. Of the 308 patients who met inclusion criteria, 291 began treatment (day treatment program: N=145; enhanced standard care: N=146), and 237 completed treatment (82% of those assigned to the day treatment program and 81% of those receiving enhanced standard care). Two hundred twenty of the patients participated in the 6-month follow-up (75% of those in the day treatment program and 73% of those in enhanced standard care provided a follow-up urine sample for screening). Both interventions were 12 weeks in duration, manual-guided, and provided by master's-level clinicians. The day treatment was an intensive, 25-hour-per-week program. The enhanced standard care was standard methadone maintenance plus a weekly skills training group and referral to on- and off-site services. Outcome measures included twice weekly urine toxicology screens, severity of addiction-related problems, prevalence of HIV risk behaviors, and program costs. RESULTS: Although the cost of the day treatment program was significantly higher, there was no significant difference in the two groups' use of either opiates or cocaine. Over the course of treatment, drug use, drug-related problems, and HIV risk behaviors decreased significantly for patients assigned to both treatment intensities. Improvements were maintained at follow-up. CONCLUSIONS: Providing an intensive day treatment program to unemployed, inner-city methadone patients was not cost-effective relative to a program of enhanced methadone maintenance services, which produced comparable outcomes at less than half the cost.

Inducing craving for alcohol in the laboratory.

Research on the mechanisms of craving often involves inducing craving in subjects in controlled settings. This article describes techniques that have been used to induce craving for alcohol, including (1) exposing subjects to actual alcoholic beverages, (2) exposing subjects to visual representations of alcoholic beverages, (3) manipulating the subjects' mood states, and (4) controlling environmental settings. The intensity of craving can be rated by the subjects themselves or can be assessed by clinicians through behavioral observations or the measurement of certain physiological responses. Success in inducing craving in the laboratory, however, has been inconsistent. Ultimately, researchers may need to monitor subjects' craving responses in actual environmental settings.

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.

Internal validity of Project MATCH treatments: discriminability and integrity.

Project MATCH (Matching Alcoholism Treatments to Client Heterogeneity) is a multisite collaborative project designed to evaluate patient-treatment interactions in alcoholism treatment. To evaluate whether major threats to the internal validity of the independent (treatment) variable in Project MATCH could be ruled out, we investigated several aspects of treatment integrity and discriminability. In this study, 1,726 alcohol-dependent participants at 10 sites were randomized to 3 treatments: cognitive-behavioral treatment (CBT), motivational enhancement therapy (MET), and 12-step facilitation (TSF). Participants received treatment either as outpatients or as aftercare following a more intensive inpatient or day hospital treatment. For both the outpatient and aftercare arms of the study, treatments were discriminable in that therapists implemented each of the treatments according to manual guidelines and rarely used techniques associated with comparison approaches. Participants received a high level of exposure to their study treatments, and the intended contrast in treatment dose between MET and the 2 more intensive treatments (CBT and TSF) was obtained. Alcoholics Anonymous involvement was significantly higher for participants assigned to TSF versus MET or CBT, whereas the treatments did not differ in utilization of other nonstudy treatments. Nonspecific aspects of treatment such as therapist skillfulness and level of the therapeutic alliance were comparable across treatment conditions.

Dose-related ethanol-like effects of the NMDA antagonist, ketamine, in recently detoxified alcoholics.

BACKGROUND: This study evaluated the dose-related ethanol-like subjective effects of the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine hydrochloride in recently detoxified alcoholics. METHODS: Twenty male inpatients meeting DSM-III-R criteria for alcohol dependence and who had not consumed alcohol for 10 to 27 days prior to the study completed 3 test days that involved the intravenous infusion of ketamine hydrochloride (0.1 mg/kg or 0.5 mg/kg) or saline solution under randomized double-blind conditions. Ethanol-like subjective effects were assessed using the Sensation Scale; the Biphasic Alcohol Effects Scale; visual analog scales to measure "high" and degree of similarity to ethanol, cocaine, and marijuana; a scale assessing the number of standard alcohol drinks producing similar subjective effects; and visual analog scales measuring ethanol craving. RESULTS: Ketamine produced dose-related ethanol-like effects on each scale measuring its similarity to ethanol. Its effects were more similar to the sedative or descending limb effects of ethanol than to the stimulant or ascending limb effects. Ketamine effects also were more like ethanol than marijuana or cocaine. Ethanol-like effects were more prominent at the higher ketamine dose, a dose rated as similar to greater levels of ethanol intoxication. However, ketamine did not increase craving for ethanol. CONCLUSION: The production of ethanol-like subjective effects by ketamine supports the potential clinical importance of NMDA receptor antagonism among the mechanisms underlying the subjective effects of ethanol in humans.

Ecological momentary assessment (EMA) with treated alcoholics: methodological problems and potential solutions.

Ecological Momentary Assessment, a methodology by which information can be obtained about phenomena as they occur in a person's natural environment, was used to assess the antecedents to relapse in treated alcohol abusers. Alcoholic participants (N = 27) were asked to record their urge to drink alcohol and their mood state, situation, and alcohol use on 5- x 7-in. record cards in response to 8 random prompts per day for 21 consecutive days after discharge from a Veterans Affairs inpatient treatment center. The purpose of the research was to determine the extent to which drinking urges occurred in the patient's home environment after treatment and to identify the mood states and alcohol-related stimuli associated with urges. Field recordings were prompted by a programmable wrist watch. Results suggested that compliance with procedures was excellent and that the occurrence of drinking and of drinking urges was relatively rare. However, significant methodological problems were brought to light that may have compromised the results. These problems are presented and potential solutions are proposed.

Alcohol cue reactivity, negative-mood reactivity, and relapse in treated alcoholic men.

Relapsed alcoholic individuals frequently report that negative emotional states trigger their return to drinking. A parametric laboratory study was conducted to assess the separate and combined effects of exposure to alcohol-related stimuli and induced negative moods in abstinent alcoholic persons. The authors also sought to determine if reactivity to alcohol cues or reactivity to negative mood induction predicted relapse soon after treatment. Men with alcoholism (N = 50) undergoing inpatient treatment participated in a guided imagery procedure designed to induce negative moods and were then exposed to either their favorite alcoholic beverage or to spring water. Results indicated that both alcoholic beverage presentation and negative affect imagery led to increased subjective reporting of desire to drink. These effects were additive but not multiplicative (i.e., the interaction of mood state with beverage type was not significant). Reported urge to drink during the trial that combined negative mood imagery with alcoholic beverage exposure predicted time to relapse after inpatient discharge.

Serotonergic and noradrenergic dysregulation in alcoholism: m-chlorophenylpiperazine and yohimbine effects in recently detoxified alcoholics and healthy comparison subjects.

OBJECTIVE: This study compared serotonergic (5-HT) and noradrenergic reactivity in recently detoxified alcoholic patients and healthy comparison subjects. METHOD: Participants were 22 male inpatients who met DSM-III-R criteria for alcohol dependence and who were abstinent for 12-26 days and 13 male healthy comparison subjects. Subjects completed 3 days of testing over 2 weeks under double-blind conditions that involved the intravenous infusions of m-chlorophenylpiperazine (mCPP), yohimbine, or a saline placebo. Drug effects on mood, physiologic responses, and plasma levels of cortisol, prolactin, and 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured. RESULTS: Both mCPP and yohimbine infusion increased nervousness, vital signs, and plasma cortisol, prolactin, and MHPG levels relative to placebo Cortisol responses to mCPP were blunted in the alcoholic patients relative to the comparison subjects. Cortisol and prolactin responses to yohimbine were greater in the alcoholic patients, whereas their pulse increases after yohimbine infusion were blunted. No group differences emerged in MHPG, nervousness, or blood pressure responses to either drug. CONCLUSIONS: This study documents persistent alterations in neuroendocrine responsivity of both 5-HT and noradrenergic systems in alcoholic patients after detoxification. Blunted cortisol responses to mCPP in these recently detoxified patients may reflect reductions in 5-HT2 receptor function. The absence of altered MHPG responses to yohimbine in the alcoholic patients suggests that presynaptic noradrenergic responsivity is not persistently altered in these patients. In contrast, the enhanced cortisol responses and reduced pulse responses to yohimbine in alcoholic patients may reflect down-regulation of postsynaptic noradrenergic receptors.

Differences between responders and nonresponders to cocaine cues in the laboratory.

Previous research has shown that a majority of drug-dependent subjects respond to drug cues in the laboratory with increased craving; however, approximately one-third are not cue responsive. The current study examined differences between responders and nonresponders to cocaine cues in a sample of 69 cocaine-dependent methadone patients. Subjects completed questionnaires assessing selected dimensions of addiction and participated in a cue-reactivity protocol that assessed both cocaine craving and cocaine aversion in response to cues. Four groups of subjects were identified on the basis of their cue responses: (a) increased craving plus decreased aversion; (b) increasing craving only; (c) decreased aversion only; (d) no increase in craving and no decrease in aversion ("nonresponders"). No group differences were found in severity of cocaine dependence, depression, or on any demographic variable, with the exception of parental status. Group differences were found on measures of cocaine expectancies and self-efficacy. There is a discussion of the bearing of these findings upon explanations offered in the literature for nonreactivity to drug cues.

Quality of life as an outcome variable in alcoholism treatment research.

Although a number of approaches to measuring alcohol consumption are available, these alone do not reflect the full range of changes that may be associated with response to treatment for alcohol abuse and dependence. What constitutes a sufficient index of response to alcohol treatment? At the very least, research should measure negative consequences of alcohol consumption, although they may be difficult to specify beyond the client's own perception. Associations between alcohol consumption and dimensions of life quality may be negative or positive in value and may be broadly or narrowly conceptualized, depending upon the aims of the study. Although models exist for the conceptualization and measurement of many aspects of quality of life in alcoholism and other fields, much remains to be specified. Still to be accomplished is a careful examination of the interrelationships between alcohol consumption and specific dimensions of life quality, particularly as these interrelationships are affected by time since treatment and client characteristics among other potential mediators and moderators. Project MATCH has attempted a broad assessment of dimensions of life quality beyond alcohol consumption. These variables are viewed as secondary, rather than primary, measures of treatment outcome. The extent to which Project MATCH's strategy was effective is a question that will be answered when we examine the interrelationships among the various dimensions of outcome and the differential effects of treatments on these outcome dimensions.

Designing studies to investigate client-treatment matching.

The process of designing studies of client-treatment matching involves a number of methodological complexities. Besides the large number of potential client characteristics and a range of possible outcome variables, a variety of treatment attributes can be matched including modality, intensity, duration, format, setting, therapist and goal. Hindsight matching designs (which can include hypothesis testing) examine interactions between client characteristics and treatments to which they were not intentionally matched. Foresight matching designs involve a prospective experimental test of a matching hypothesis, comparing the outcomes of cases matched by specific decision rules with other cases not so matched. Under certain conditions, these hindsight and foresight matching designs are logically equivalent. Mathematical modeling of clinical judgment offers yet another promising avenue for future studies of matching schemas. Glaser's core-shell strategy provides a practical model for implementing clinical systems and research on matching within ongoing services.

Assessment issues and strategies in alcoholism treatment matching research.

Sensitive and comprehensive client assessment entails complex conceptual and methodological considerations. Such activity is at the heart of matching clients to appropriate treatments. This article begins by specifying the goals and functions of assessment to support matching. This is followed by a discussion of the strategies employed in Project MATCH to identify matching and outcome variables. The assessment battery used in Project MATCH is next described. Finally, an overview of issues surrounding administration of assessment measures is provided. Particular attention is given to the topics of sequencing and timing of measures.

Relationship between role-play measures of coping skills and alcoholism treatment outcome.

Alcoholic clients were given role-play tests, involving various social and drinking-related scenarios, before and after two types of aftercare treatment. The assessments were used both to evaluate the effects of treatment and to determine whether any dimensions of pretreatment role-play performance interact with treatment type to predict treatment outcome. Eighty-nine patients were randomly assigned to aftercare group treatment involving either interactional therapy or coping skills training. Clients in both treatments experienced declines in their urge to drink during the role-play scenes from pre- to posttreatment, and these declines were related to reductions in heavy drinking. Three pretreatment role-play variables interacted with type of treatment to predict outcome: observer-rated skill, observer-rated anxiety, and self-reported urge to drink. In general, those patients who did better in the role plays had better drinking outcomes following interactional therapy. Those who experienced more difficulty in the role plays fared best with coping skills training. The results suggest that role-play measures could be used for patient-treatment matching, although it remains to be determined whether they will be superior to more easily assessed patient characteristics.

Types of alcoholics, II. Application of an empirically derived typology to treatment matching.

Data from 79 male alcoholics who were randomly assigned to either coping skills training or interactional group psychotherapy were used to replicate a multidimensional, empirically derived typology and to evaluate the typology's usefulness in matching patients to treatment. Consistent with previous cluster analysis research, indicators of risk for alcoholism, alcohol dependence, drinking history, and psychopathological impairment distinguished alcoholics along two broad dimensions of vulnerability and severity, with one subtype (type B alcoholics) manifesting an earlier onset of problem drinking, more familial alcoholism, greater dependence on alcohol, and more symptoms of antisocial personality than the other subtype (type A alcoholics). Analyses of outcome indicated that type A alcoholics fared better in interactional treatment and more poorly with coping skills training. Conversely, type B alcoholics had better outcomes with the coping skills treatment and worse outcomes with interactional therapy. Differences in treatment response were maintained for 2 years from the beginning of aftercare treatment.

Measuring treatment process in coping skills and interactional group therapies for alcoholism.

An instrument designed to measure components of two distinct alcoholism aftercare treatments was developed and evaluated for reliability and validity. Trained judges reliably rated audiotaped samples of coping skills and interactional group therapy sessions. Coping skills groups engaged in significantly more education and skill training, problem solving, and role playing. Interactional groups showed more interpersonal learning, expression/exploration of feelings, and here-and-now focus. Groups that employed more education and skill training, less expression and exploration of feelings, and less here-and-now focus were associated with fewer members reporting subsequent drinking-related problems. None of the ratings of group activities was related to abstinence.

Matching alcoholics to coping skills or interactional therapies: two-year follow-up results.

Ninety-six subjects were recruited from an inpatient alcoholism treatment program and randomly assigned to aftercare group treatment with either coping skills training or interactional therapy. Survival analyses using 2-year outcome data provided evidence for the durability of matching interaction effects. The data supported a priori hypotheses that individuals scoring high on measures of sociopathy or global psychopathology have better outcomes in coping skills treatment, whereas patients low on these dimensions have better outcomes in interactional treatment. Contrary to the original hypothesis, patients with cognitive impairment had better outcomes in interactional treatment, and patients without cognitive impairment did better in coping skills treatment.