A Controlled Trial of Cue Exposure Treatment in Alcohol Dependence

Transcription

1 Page 1 of 14 Journal of Consulting and Clinical Psychology August 1994 Vol. 62, No. 4, by the American Psychological Association For personal use only--not for distribution. A Controlled Trial of Cue Exposure Treatment in Alcohol Dependence D. Colin Drummond Addiction Research Unit, National Addiction Centre Institute of Psychiatry Steven Glautier Addiction Research Unit, National Addiction Centre Institute of Psychiatry ABSTRACT The clinical effectiveness of cue exposure (CE) treatment in alcohol dependence was evaluated in a controlled trial. Thirty-five men who were detoxified and severely alcohol dependent received either CE or relaxation control (RC) treatment. CE Ss had 400 min exposure to the sight and smell of preferred drinks over 10 days in a laboratory setting. RC Ss spent identical time in the laboratory but had relaxation therapy and only 20 min exposure to alcohol cues. During 6-month follow-up, personal interview was achieved with 91% of Ss. CE Ss had a more favorable outcome than the RC Ss in terms of latency (length of time) to relapse of heavy drinking ( p <.01) and total alcohol consumption ( p <.05). Significant predictors of latency to heavy drinking and dependence included skin conductance level ( p <.001). and experimental condition ( p <.01). Results point to the potential importance of cue exposure as a treatment for addictive behavior. This research was supported by Medical Research Council Programme Grant No We thank Colin Taylor and Griffith Edwards for comments on a draft of this article. We thank the staff and patients of the Maudsley Hospital for their helpful cooperation in this study. Correspondence may be addressed to D. Colin Drummond, Division of Addictive Behaviour, St. George's Hospital Medical School, Hunter Wing, Cranmer Terrace, London, United Kingdom, SW17 ORE. Electronic mail may be sent to [email protected] Received: May 4, 1993 Revised: October 25, 1993 Accepted: October 25, 1993 Stimuli (or cues) associated with the ingestion of dependence-producing drugs have been repeatedly shown to have important response-eliciting properties in both animals and humans. There is evidence to support the view that, after repeated drug administration, cues that precede drug ingestion (such as the sight and smell of a glass of beer or the sight of a needle and syringe) elicit conditioned responses (for reviews, see Drummond, Cooper, & Glautier, 1990 ; Niaura et al., 1988 ). Furthermore, in the case of alcohol, the intensity of the response is positively related to the subject's degree of dependence ( Corty, O'Brien, & Mann, 1988, Glautier & Drummond, 1994 ; Kaplan, Meyer, & Stoebel, 1983 ; Laberg, 1986 ). This adds more weight to a conditioning model of responses to pre-ingestion cues: Those with a higher degree of dependence will have experienced a greater frequency of drug-cue pairings and will be more likely to have experienced drug withdrawal, which is viewed as a powerful motivating factor in the maintenance of drug-taking behavior ( Edwards, 1990 ).

2 Page 2 of 14 Such evidence has pointed to the potential of cue exposure as a treatment in drug and alcohol dependence. It has been suggested that repeated exposure to pre-ingestion cues in the absence of drug ingestion will lead to extinction of conditioned responses, thus reducing the likelihood of relapse to drug-taking behavior ( Drummond, Cooper, et al., 1990 ). An alternative strategy has been proposed in which the drug taker is given an initial priming dose of the drug and encouraged to resist the temptation to consume more of an available drug ( Rankin, Hodgson, & Stockwell, 1983 ). Such a treatment aims to enhance self-control of drinking behavior rather than maintaining abstinence and has similarities to cue exposure and response prevention in obsessive compulsive neurosis. Although one priming dose response prevention study with participants dependent on alcohol showed that drinking behavior could be modified in a laboratory setting ( Rankin et al., 1983 ), this method has not been tested in a clinical follow-up study. Indeed, at the time of writing, we did not find a single published clinical trial of the former method of cue exposure in alcohol dependence. The results of cue exposure treatment trials in the case of heroin and nicotine dependence have so far not supported its effectivenss ( Dawe et al., 1993 ; McLellan, Childress, Ehrman, & O'Brien, 1986 ; Raw & Russell, 1980 ). This stands in contrast to the evidence for the effectiveness of cue exposure in the analogous condition of phobic neurosis ( Beech & Vaughan, 1978 ; Mathews, Gelder, & Johnston, 1981 ). In an unpublished manuscript from this controlled trial of cue exposure in individuals with severe alcohol dependence, we compared the effects of exposure to pre-ingestion cues on physiological and subjective responses in a laboratory setting with those of a control procedure involving relaxation training ( Drummond & Glautier, 1993 ). A significiant reduction in subjective tension was found in the cue exposure group, compared with the finding in the control group. Physiological responses were not, however, significantly influenced by cue exposure in comparison with controls, although both groups showed reductions in responsivity over time. In this article we examine the clinical effects of exposure to pre-ingestion cues. The main hypothesis was that cue exposure would reduce the likelihood of relapse following the patient's discharge from the hospital. More particularly, it was predicted that the effect of cue exposure would be an increased latency (or length of time) to initial lapse rather than to full reinstatemnt of dependence, given that the mechanism of treatment proposed by conditioning theory was extinction of responsivity. Hence, it was expected that following initial lapse, any benefits accrued through cue exposure would be lost because of reinstatement of conditioned responding. An alternative theory, however, was that the cue exposure subjects would acquire cognitive coping skills and increased selfefficacy in resisting the temptation to drink by virtue of practice in resisting temptation during treatment ( Drummond, Cooper, & Glautier, 1990 ; Marlatt, 1990 ). It was possible that, if such skills were acquired during treatment, they could exert an effect not only on latency to intial lapse but also on the subjects' capacity to exercise control over their alcohol consumption following initial lapse. The study design had two important strengths in relation to testing these hypotheses. First, experimental and control subjects were provided with a similar rationable for treatment, and they received an identical amount of exposure to the therapists and to the laboratory environment. It was felt to be important to control, as far as possible, for the nonspecific effects of treatment ( Bergin & Lambert, 1978 ). Second, the inclusion of subjective and physiological measures of responsivity in the laboratory setting allowed the examination of the elements of treatment that were important in predicting treatment outcome. In the results presented here, we report first on a comparison of clinical outcome between the two treatment groups and then examine the possible factors that are predictive of treatment outcome. The subjects and methods have been described in detail in relation to the laboratory phase of the study in an unpublished manuscript ( Drummond & Glautier, 1993 ) but will be reiterated here in brief. Method

3 Page 3 of 14 Subjects Subjects were recruited from the Maudsley Hospital Alcohol Clinic. Altogether 108 male patients who had been referred to the clinic, mainly by general practitioners, for help with their drinking problems were assessed for their suitability to enter the trial. Sixty-three (58%) were deemed to be unsuitable by virtue of having one or more of the following diagnoses: concurrent severe physical or mental illness, brain damage, social instability, or an insufficiently severe degree of alcohol dependence. All suitable potential subjects ( N = 45) had a core of greater than 25 on the Severity of Alcohol Dependence Questionnaire (SADQ; Stockwell, Hodgson, Edwards, Taylor, & Rankin, 1979 ), a diagnosis meeting the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev.; American Psychiatric Association, 1987 ) criteria for severe alcohol dependence, and a goal of complete abstinence. Of the 45 patients offered entry to the trial, 9 declined and 36 (33% of the screened sample) were admitted. One subject subsequently withdrew from the trial following admission but before commencement of treatment, thus leaving 35 who completed the trial. (See Results section and Tables 1 and 2 for a description of the sample characteristics). Initial Clinical Assessment At first contact in the clinic, all subjects were assessed using a standardized, semistructed interview method that we designed to elicit personal, psychiatric, and drinking histories. We measured alcohol consumption during each of the previous 26 weeks using a standardized interview method ( Drummond, Thom, Brown, Edwards, & Mullan, 1990 ). The SADQ and Alcohol Problems Questionnaire (APQ; Drummond, 1990 ) were administered to provide a measure of the severity of dependence and the occurrence of problems related to drinking, respectively, druing the previous 6 months. The APQ score is used here and consists of the first 23 items of the APQ, applicable to all subjects. Social stability was assessed using the Straus Bacon Index ( Straus & Bacon, 1951 ). On this 5-point scale, subjects receive 1 point for the presenc of each of the following criteria: stable employment over the past 3 years, stable residence for the past 2 years, current residence with at least 1 other individual (not currently living alone), and a current marital (or cohabiting) relationship. This Index has previously been shown to be predictive of treatment outcome (e.g. Vaillant, 1983 ). Mental and physical state examinations were supplemented by blood investigations including urea and electrolytes, liver function, and serology. When patients provided their informed verbal consent to participate in the study, they were placed on the waiting list for admission to the inpatient unit. Admission took place after a mean of 16.7 days (data missing in 4 cases), with no significant difference in wait times between conditions (cue exposure group, M = 16.5 days, SE = 4.6; relaxation control group, M = 17.1 days, SE = 4.4; t (1, 31) = 0.1, p = ns ). Verbal information was supplemented by a written description of the treatment, which the patients took home to read at their leisure. Written consent to participate was not obtained until patients had been admitted and detoxified so that they could consider their participation in a sober state. Treatment Procedure All subjects underwent detoxification with decreasing doses of chlordiazepoxide, which was titrated by the ward staff to the needs of the individual. Routine medical, nursing, and social care was provided as appropriate. All subjects were required to attend ward group therapy twice weekly and encouraged to attend Alcoholics Anonymous once weekly. A standard occupational therapy program was offered to the subjects. Subjects were encouraged not to leave the ward until detoxification was completed. The mean length (days) of inpatient stay did not differ between conditions (cue exposure group, M = 46.2 days, SE = 5.3; relaxation control group, M = 39.3 days, SE = 3.2; t (1, 35) = 1.0, p = ns ).

4 Page 4 of 14 Treatment assignment. Subjects were sequentially assigned to either the cue exposure or the relaxation control group. The cue exposure group ( n = 20) was recruited first, and the relaxation control group ( n = 15) was recruited second. The size of the treatment groups differed because the time available for recruitment expired. Sequential assignment was preferred to random assignment to minimize the possibility of subjects becoming aware that different treatments were used through discussing their treatment with other subjects in the inpatient unit at the same time. Subjects' unawareness of their assignment was of paramount importance in ensuring that as far as possible the two groups were matched in terms of beliefs in the value of the treatment they were to receive. The relaxation control treatment was described to both staff and patients as cue exposure plus relaxation treatment rather than as a control treatment. Treatment rationale. Before the treatments were started, subjects were given a standard treatment rationale that differed between the two treatment groups. The cue exposure group was told that a reason commonly given for relapse was difficulty in resisting the temptation to drink in situations where alcohol was available. The purpose of the study was therefore the assessment of whether the exposure to the sight and smell of alcohol is a helpful treatment. Subjects were told that they could use the treatment sessions as an opportunity to gain confidence in resisting the temptation to drink. The treatment, however, would not necessarily abolish their desire to drink in the future. They were asked not to drink the alcohol presented in the sessions, but we told them that no sanctions would be taken against them should they choose to do so. This was to increase as far as possible the perceived availability of alcohol, while at the same time avoiding presenting them with an overwhelmingly difficult task. Only 1 subject (Subject 7, a cue exposure subject) took a sip of the drink during one session, but then the subjects spat out the alcohol and completed the session per the protocol. The relaxation control group was given the same rationale as the cue exposure group for the cue exposure element of their treatment, but in addition they were told that a reason commonly given for relapse was difficulty with tension in situations where alcohol was available. Therefore, the purpose of the study was the assessment of whether a combination of relaxation training and exposure to the sight and smell of alcohol is a helpful treatment. They were also told that they could use the treatment sessions both to gain confidence in resisting the temptation to drink and to learn relaxation techniques that they could put into practice in difficult drinking situations in the future. The relaxation control group was also given a standard introduction to relaxation therapy as described by Bernstein and Borkovek (1973). Cue hierachy. All subjects were asked to nominate their favorite, most commonly consumed, alcoholic drink (highsalience alcohol stimulus); a second, less commonly consumed, alcoholic drink (low-salience alcohol stimulus); and a soft drink (neutral stimulus) that had little or no alcohol association. These drinks were then used to construct a cue hierarchy for later use in the treatment sessions. Cue responsivity test procedure. All subjects underwent a cue responsivity test procedure on Days 1, 5, 6, and 10 of the 10-day treatment course. This is described in detail in an unpublished manuscript ( Drummond & Glautier, 1993 ) but is reiterated here, in brief. The procedure was conducted in a sound-insulated room with the subject seated in a comfortable chair. The subjects were connected to physiological recording transducers at the

5 Page 5 of 14 beginning of each session. The experimenter was able to observe the subject through a one-way mirror from an adjacent room. Communication between the subject and experimenter was through headphones. At predetermined points, the subject was asked to lift an opaque container that concealed either an alcoholic or a neutral stimulus and then to act out drinking for a period of 5 min without consuming the drink (i.e., picking up, looking at, smelling, and thinking about the drink all without consuming the drink). Finally the subjects were told to replace the drink on the table and to cover it with the opaque container. Both an alcoholic and neutral stimulus were presented on each test day in a counterbalanced order. The low-salience alcohol stimulus was presented on Days 1 and 5, and the high-salience alcohol stimulus was presented on Days 6 and 10. The drink stimuli were presented in the subjects' preferred manner (e.g., a glass of whisky or a can of beer). All test procedures and treatment sessions were conducted by one of two therapists (one research psychologist nurse [Steven Glautier] and one research psychiatrist [D. Colin Drummond]). Each subject had the same therapist throughout treatment, and both therapists administered both treatments to approximately the same number of subjects in each experimental condition. To ensure comparability between therapists in the conduct of treatment and test procedures, therapists followed a detailed written protocol. Furthermore, pilot work carried out before the trial involved both therapists being present during pilot sessions to standardize procedures. Subject compliance with the test and treatment procedures was ensured by having detailed instructions for subjects and a familiarization procedure before the beginning of treatment. Cue exposure treatment. After an initial familiarization session, cue exposure subjects were exposed to alcohol stimuli for a period of 40 min per day, and they were exposed to a neutral stimulus for 10 min per day, as far as possible on 10 consecutive weekdays. On cue responsivity test days, exposure to the alcohol stimulus continued for a period of 35 min, and in the case of the neutral stimulus, for a period of 5 min, after the end of the respective test period. During each exposure period, cue exposure subjects were asked repeatedly to handle the drink stimuli in the same manner as in the test period. So the total duration of alcohol stimulus exposure in the cue exposure group was 400 min (including 200 min with the lowsalience stimulus and 200 min with the high-salience stimulus). The low-salience alcohol cue was always presented for the first block of 5 days, and the high-salience stimulus was presented for the second block of 5 days. At the end of each session, the experimenter debriefed the subject before returning him to the inpatient unit, and subjects were advised not to leave the ward immediately after each treatment session to minimize the possibility of encountering a drinking situation outside the unit in an aroused state. Relaxation control treatment. The relaxation control group spent the same amount of time in the laboratory as the cue exposure group. The relaxation control subjects were only exposed to the alcoholic and neutral stimuli only on the test days, for a period of 5 min per stimulus. The remainder of the test sessions was designated a rest period during which subjects were instructed to relax. On the remaining 6 days the relaxation control group underwent Progressive Relaxation Training according to the method of Bernstein and Borkovek (1973) to allow standardization of procedure between subjects. The relaxation control group, therefore, received a total of 20 min exposure to alcoholic stimuli over the 10 treatment days (one twentieth of the cue exposure group alcohol exposure).

6 Page 6 of 14 Discharge and follow-up. In a debriefing session following treatment, all subjects were advised to abstain from alcohol following their discharge from the hospital. Subjects were then discharged, normally within a few days of completing the treatment sessions. All subjects were followed up for 6 months by the therapists, who were aware of the treatment assignment. Follow-up interviews were normally conducted in the outpatient clinic, but if a subject failed to attend appointments the interviewer made repeated visits to the subject's home until contact could be made. In a few cases where it was impossible to interview the subject in person, information about the subject's condition was obtained either by telephone interview with the subject or from the subject's spouse or general practitioner. The interviewer aimed to make contact with the subject at the 1-, 3-, and 6-month points following discharge from hospital. The adequacy of follow-up is detailed later. Measures Cue responsivity data. Physiological and subjective measurements were made during treatment sessions. However, we are concerned here only with the final treatment session (Session 10) measures as predictors of treatment outcome. Data on all test sessions are presented in an unpublished manuscript ( Drummond & Glautier, 1993 ). Physiological measures included skin conductance level, cardiac interbeat interval, finger pulse volume, and forearm electromyogram. All subjects were connected to physiological transducers at the beginning of the sessions. Signals were digitized with a Contact Precision Instruments PsyLab Data Acquisition Unit and stored on an IBM-compatible personal computer. A software program was designed to convert the raw data into mean values for each 30-s period during the cue responsivity test procedures. Beccause the peak response to the stimuli on different physiological measures occurred at different time points during the 5-min periods following exposure, the 30-s period of maximum response was selected for further analysis. Because responses occurred in different directions for different measures ( Drummond, Cooper, & Glautier, 1990 ; Glautier, Drummond, & Remington, 1992 ), maximum skin conductance level and electromyogram responses and minimum interbeat interval and finger pulse volume responses were selected. Responses to the neutral stimulus were subtracted from the response to the alcohol stimulus to produce a response difference score for each measure. All physiological measures used in this experiment were made according to standard protocols in terms of transducer placement. Questionnaires were completed at predetermined points during each test session. The questionnaires consisted of 7-point Likert-type scales ranging from not at all (1) to very much (7) and including these questions: "How much do you want a drink?" (desire) and "How tense do you feel?" (tension). This was the first experiment in which these questionnaires had been used. It was not possible to determine the test retest reliability of the scales because the experiment was designed to bring about change in these measures both within and across sessions. It was possible, however, to establish the validity of the questionnaires. We found that the two scales were significantly correlated with each other, with both physiological measures, and with the SADQ ( Glautier & Drummond, 1994 ), which was consistent with theoretical predictions and previous research findings ( Drummond, Cooper, & Gluatier, 1990 ). Both desire and tension were significantly greater during exposure to alcohol compared with neutral stimuli. Furthermore, we found that changes in tension and desire during treatment were consistent with the theoretical predictions (although this was statistically significant only in the case of tension, Drummond & Glautier, 1993 ). Together these findings suggest that the scales had an acceptable degree of validity. Treatment outcome data. At each of the three follow-up points, detailed information was obtained concerning the subjects' drinking behavior and the occurrence of withdrawal symptoms if drinking had taken place. The method

7 Page 7 of 14 used to collect the drinking history was identical to that described in relation to the intake assessment. Because latency to initial lapse and reinstatement were key variables of interest, the day on which drinking began and those days on which subsequent progression or regression of drinking and symptoms of dependence took place were established by retracing with the subject, their movements and the occurrence of key events (often the occurrence of major news or sporting events, birhdays, anniversaries, etc.). Data from the interviews were used to establish a picture of drinking over the whole 6-month period. The APQ was also administered at, or as closely as possible to, the 6-month pont. Hospital records were examined and any clinical staff (other than the two therapists) who had contact with the subjects during the follow-up period were interviewed to confirm the subjects' account of events. The interviewers also contacted other treatment agencies with whom the subjects had been involved (e.g., rehabilitation centers and probation officers) for the same purpose. Previous research has shown the APQ to have a high degree of test retest reliability as well as both construct and concurrent validity ( Drummond, 1991 ; Williams & Drummond, in press ). The drinking measure used for the pre-intake and follow-up periods has previously been found (a) to be correlated with both the APQ and the SADQ and (b) to be responsive to treatment interventions in these studies. Data Analyses Two separate sets of analyses were conducted on the outcome data. The first set considered differences in outcome between the two treatment groups. We compared the intake characteristics between the two groups using t tests and chi-square tests, as appropriate, to assess the adequacy of group matching. Any variables that showed differences at ( p <.25), SADQ and Straus Bacon Index, were then included in subsequent analyses of outcome to ensure that even small differences between the groups did not bias the analysis of outcome. Quantity of alcohol consumption during each day of the follow-up period was classified into one of six drinking level categories: Level 0, no drinking; Level 1, >0 and <=10 units of alcohol; Level 2, >10 and <=20 units; Level 3, >20 and <=30 units; Level 4, >30 and <=40 units; Level 5, >40 units (1 unit = 8 g ethanol). Latency in days from the time of discharge to reaching 3 consecutive days of drinking at each level (>0) was computed, thus there were 5 latency scores. If a level was not reached during the follow-up period, a score of 182 was returned. Latency to first morning drink and the emergence of morning withdrawal symptoms were also computed as number of days from the time of discharge to 3 consecutive days of either morning drinking or morning withdrawal symptoms. A total drinking score for the whole 6-month period was computed. Each week of the 26-weeks of follow-up was classified according to the maximum level of drinking on three consecutive days. The number of weeks spent in each level of drinking was multiplied by the median number of units of alcohol for that level, and the posttreatment total drinking score was computed as the sum of the weekly scores. The total drinking scores for the 6-months prior to treatment was computed in the same manner. We subjected each outcome measure to a t test comparing the cue exposure and relaxation control groups to provide an indication of the size of the effect of experimental condition. However, because the latency data are "right-censored" (i.e., not all subjects had relapsed at the 6-month follow-up point), and because marginal differences between the groups were found at intake, a more complex analysis was required. Event history analysis with maximum likelihood logistic regression was the analytic method that we used for this purpose ( Allison, 1984 ). Logistic regression analysis then estimated the effect of explanatory variables (in this case experimental condition, SADQ, and Straus Bacon Index) on the risk of relapse to each drinking level. The SPSSPC logistic regression procedure was used here ( Norusis, 1990 ). The second set of analyses concerned predictors of treatment outcome. Potential predictors of outcome were entered into a regression analysis with backward elimination using the SPSSPC backward

8 Page 8 of 14 procedure with the alpha level set at 0.1. Three types of variable were considered as potential predictors of clinical outcome: pre-treatment factors (Straus Bacon Index, SADQ, pretreatment total drinking score, APQ score, length of drinking problem, family history of drinking problems), treatment factors (experimental condition, length of inpatient stay) and posttreatment factors (cue responsivity measures on Day 10). Adequacy of Matching at Intake Results Tables 1 and 2 show a comparison of sociodemographic and drinking variables between the cue exposure and relaxation control groups at intake. As a whole, the two groups were older, less socially stable, more alcohol dependent, and experiencing a greater level of alcohol-related problems than is typical of attenders at the Maudsley Hospital Alcohol Clinic ( Drummond, Thom, et al., 1990 ). This can be accounted for by our selection for severity of alcohol dependence. It is of interest that overall, 71.5% of the sample had a positive family history of alcohol problems, which is higher than is generally typical of other series. Overall, the results show that the two groups were broadly similar and adequately matched at ( p <.1). At ( p <.25), however, the relaxation control group was more alcohol dependent and more socially stable than the cue exposure group. Because of the potential importance of these variables in terms of outcome, they were included in subsequent analyses, where appropriate. Treatment Outcome Adequacy of follow-up. Follow-up was achieved by personal interview in 32 cases (91.4%) over the 6-month period, 100% follow-up in the relaxation control group and 85% in the cue exposure group. At the 1-, 3-, and 6-month points, personal follow-up was achieved with 93%, 80%, and 69% of the subjects, respectively. In all other cases information on outcome was obtained through a combination of telephone interviews with subjects and interviews with spouses, general practitioners, and other health professionals involved in the subjects' care. In one case (a cue exposure subject), death occurred during follow-up after a relapse. However, information concerning drinking behavior before death was available. Where information was incomplete or equivocal, a poor outcome was assumed, and the appropriate pretreatment values were returned in the case of posttreatment total drinking score, maximum drinking level, and APQ score. In all cases where relapse, full reinstatement, or both had occurred it was possible to establish latency values through a combination of the above information sources. A strict criterion of personal interview with the subject was required to record total abstinence or moderate drinking for any period during the follow-up. Comparison of treatment outcome. Table 3 displays the mean values on the outcome measures for the two treatment groups. In each case, mean latencies were longer in the cue exposure group than in the relaxation control group. Furthermore, the cue exposure group had a lower overall posttreatment total drinking score and APQ score. The t tests indicated that these differences were significant ( p <.05) on all variables except latency to drinking at Levels 1 and 2 and on the APQ score. There was no significant difference between the groups in terms of latency to first drink (cue exposure, M = 61.1, SE = 16.0; relaxation control, M = 45.3, SE = 15.8; t (1, 35) = 0.7, p = ns ) or in the number completely abstinent over the 6-month follow-up period (cue exposure, n = 4; relaxation control, n = 2; χ 2 1, N = 35 = 0.3, p = ns ).

9 Page 9 of 14 The results of the logistic regression analyses of the latencies ( Table 4 ) showed broadly similar effects of experimental condition when we compared them with the simple t tests, but the results of the logistic regression analyses are more supportive of an advantage of cue exposure over relaxation control treatment. Six out of seven of the analyses are significant ( p <.05). At Level 1, experimental condition accounts for 5% of the variance in outcome (controlling for Straus Bacon Index and SADQ score) and rises to 14% of variance in Level 3 relapse. Straus Bacon Index is a significant predictor of relapse in all cases, whereas SADQ score is not. Predictors of Treatment Outcome The purpose of this phase of the analysis was twofold. First, because of the potentially large number of factors that might influence outcome, we examined the relative importance of cue responsivity compared with other factors in this regard. Second, such an analysis allows an exploration of the possible mechanism of treatment effects. The results of multiple regression analyses of predictors of treatment outcome with backward elimination are displayed in Table 5. The pretreatment factors of family history and social stability were significant predictors of latency to the lower levels of drinking (from Level 1 to Level 4) and together accounted for between 20% and 40% of the variance in outcome. The direction of the effects shows that those with a family history of alcohol abuse and with lower social stability have a shorter latency to relapse. Level of alcohol-related problems was a significant predictor at Levels 3, 4, and 5 and of posttreatment problems. Those with a higher pretreatment APQ score had a shorter relapse latency and a higher posttreatment APQ score. Responsivity, on the other hand (particularly in the form of skin conductance level), became an important predictor of treatment outcome in terms of latency to heavier drinking and the onset of reinstatement of withdrawal symptoms. Skin conductance accounted for between 6% and 22% of the variance in outcome, moving from Level 3 to Level 5, and between 26% and 27% of the variance in latency to morning drinks and withdrawal, respectively. Finger pulse volume accounted for between 20% and 21% of the variance in latency to reinstatement of morning drinking and withdrawal symptoms. Severity of dependence was not a significant predictor of any of the outcome variables. In general, the results suggest that initial lapse tends to be predicted by pretreatment factors, whereas reinstatement tends to be predicted by responsivity. Experimental condition was a significant predictor of all outcome variables, when level of responsivity was controlled for, with the exception of latency to Level 1 drinking and posttreatment APQ score. The direction of the effect of experimental condition was the same as in the results of the previous analyses, namely that the cue exposure groups has a longer latency to relapse and a lower posttreatment total drinking score. The effect of experimental condition as a predictor variable is first apparent at Level 2 where it accounts for 7% of the outcome variance, and it increases to account for 14% of the variance in latency to very heavy (Level 5) drinking. Overall, experimental condition accounted for a significant amount of outcome variance in its own right (i.e., when responsivity is controlled for). Discussion The results of this study suggest that overall, the cue exposure group had a more favorable outcome than did the control group in terms of latency of reinstatement of heavier drinking and dependence and in the overall quantity of alcohol consumed during follow-up. The results with respect to latency to initial lapse (Level 1) also favor the cue exposure group, but they fall short of significance. The same is the case for the experience of alcohol-related problems. It appears therefore that the effects of cue exposure become increasingly apparent after the point of initial lapse. It was also found in the regression analyses

10 Page 10 of 14 of predictors of outcome that experimental condition and responsivity independently predicted outcome in terms of latency to reinstatement of heavier drinking and dependence. Together these findings suggest that the mechanism of cue exposure may be more complex than that proposed by a model in which treatment effects are simply mediated by responsivity. Possible mechanisms for the clinical effects of cue exposure are discussed later. As in previous follow-up studies of dependent drinkers, pretreatment social stability and level of alcohol-related problems both emerged as significant predictors of treatment outcome ( Armor, Polich, & Stambul, 1978 ; Gibbs & Flanagan, 1977 ; Orford & Edwards, 1977 ; Vaillant, 1983 ). Dependence, on the other hand, did not significantly predict outcome. The finding of family history of drinking problems as a significant predictor of outcome was unexpected. Family history has been found to predict the development of alcohol problems rather than the clinical outcome ( Vaillant, 1983 ). It is of interest, however, that responsiveness to alcohol cues has previously been shown to be related to a family history of alcohol problems ( Newlin, 1985 ). Furthermore, Schuckit (1984, 1985) reported differences in physiological and subjctive responsiveness to the effects of alcohol between nonclinical subjects with a family history of drinking problems and controls. Whatever the reason for our finding of the predictiveness of family history, it certainly warrants further investigation. What confidence can be placed in the findings of thus study? Although the study had a relatively small sample size, it is not the case that the advantage of cue exposure was manifest in only one out of a series of outcome measures. Significant differences were found on most of the measures used. Furthermore, although several statistical tests were performed in a relatively small sample, they were designed to test a priori hypotheses rather than representing a "fishing" exercise. Nevertheless, one should be cautious in interpreting results that approach significance in view of the sample size. The fact that the two groups did not differ significantly in terms of alcohol-related problems (although this pointed in the same direction as other measures) may be because such problems do not depend simply on the level of alcohol consumption in a given period ( Drummond, 1990 ). However, overall, the results provide a coherent picture in terms of differences between the groups. Are the observed statistically significant differences in outcome also clinically significant? Significant treatment effects emerged in latency to reach Level 2 drinking (drinking more than 10 units per day for 3 consecutive days) as well as being reflected in the posttreatment total drinking score for the 6-month follow-up period. If complete abstinence was regarded as the only acceptable outcome, we would have to say that cue exposure showed no advantage over control treatment. However, there are many outcomes that fall short of complete abstinence but represent significant improvements in drinking behavior ( Hesselbrock, Babor, Hesselbrock, Meyer, & Workman, 1983 ). Therefore, it would be wrong to reject a treatment outright because it does not meet a strict criterion of complete abstinence if it otherwise provides significant benefits. This is particularly so in a condition where few treatments, if any, have been shown to be beneficial. We conclude that statistically significant increases in latency to Level 2 drinking and above, and an overall reduction in posttreatment total drinking score represent clinically significant harm-reduction outcomes because there is considerable evidence that the harmful effects of drinking increase in proportion to the level of alcohol consumption. What does this study tell us of the mechanism of cue exposure? Both treatment assignment and responsivity (in the form of skin conductance level on the final day of treatment) are independently predictive of treatment outcome. Thus the effects of cue exposure do not appear to be simply mediated by responsivity (as we have measured it). Furthermore, the earlier section of the study into the effects of cue exposure in the laboratory setting ( Drummond & Glautier, 1993 ) did not demonstrate significant effects of treatment on physiological responsivity, including skin conductance. However, differences in subjective tension did emerge during the course of treatment.

11 Page 11 of 14 It has previously been suggested that a potential mechanism of cue exposure is in relation to the acquisition of coping skills ( Drummond, Cooper, & Glautier, 1990 ; Marlatt, 1990 ). It may be the case that subjects developed increased self-efficacy and were able to apply effective coping skills in resisting heavier drinking after a drinking episode had begun. This conclusion is compatible with the findings of Rankin et al's (1983) priming dose treatment study. Our study raises the question of whether a person who drinks could apply cognitive coping skills after a lapse to 10 to 20 units of alcohol per day. This seems unlikely if drinking at Level 2 was continuous and taking place over a prolonged period. However, the latency measures only indicate length of time to 3 consecutive days of drinking at a particular level: They tell us nothing about drinking thereafter. Hence, it is possible to speculate that some cue exposure subjects stopped or reduced their drinking after an initial lapse, thus delaying or preventing progression to a higher drinking level. Overall, no simple mechanism is supported by the results, and we do not present the situation as being a test of classical conditioning versus cognitive models of cue exposure's effects: The study was not designed to do this. Furthermore we see these two models as being complementary rather than competitive. The findings do however highlight several important future research questions. The aim of this study was to evaluate the effects of cue exposure in a tightly controlled protocol to allow for a valid comparison of cue exposure with a credible control therapy given for an equal duration. It may be more important in practice to deliver cue exposure in a more individually tailored way, as is commonly practiced with cue exposure treatment for phobic neurosis. Furthermore, no specific cognitive therapy was used in this study because of its potential to interfere with physiological recording of responsivity and because it would have added another treatment dimension to examine. It is possible that the effects of cue exposure may be enhanced by encouraging the development of specific cognitive coping in the context of the cue exposure sessions. It may also be advantageous in terms of subsequent generalization, for researchers to conduct cue exposure treatment in the natural drinking environment ( Blakey & Baker, 1980 ; Drummond, Cooper, & Glautier, 1990 ). Finally, this study points to three methodological approaches that could assist in the development of further cue exposure clinical research and in treatment outcome research in the addictions field generally. Our analysis of outcome in terms of latency to drinking at increasing levels and of reinstatement of dependence provides a more detailed method of studying outcome than a simple comparison of relapse versus abstinence or overall consumption during follow-up. Indeed the process of relapse itself warrants further investigation in this way, because it extends the distinction between lapse and relapse ( Marlatt, 1985 ). Second, we argue that this study shows the importance of using adequate controls when studying treatment effects, particularly in cue exposure research. Third, we have illustrated the value of regression analysis as a means of assessing treatment outcome by observing that there are many factors, in addition to treatment assignment, that are important determinants of outcome. This further highlights the dangers of relying too heavily on a simple unitary treatment approach toward a complex and multifaceted problem such as alcohol dependence. References Allison, P. D. (1984). Event history analysis: Regression for longitudinal event data. (Beverly Hills: Sage) American Psychiatric Association. (1987). Diagnostic and statistical manual of mental disorders (3rd ed. re.).(washington, DC: Author) Armor, D. J., Polich, J. M. & Stambul, H. B. (1978). Alcoholism and treatment. (New York: Wiley) Beech, H. R. & Vaughan, M. (1978). Behavioural treatment of obsessional states. (New York: Wiley) Bergin, A. E. & Lambert, M. J. (1978). The evaluation of therapeutic outcomes.(in S. L. Garfield & A. E. Bergin (Eds.) Handbook of Psychotherapy and Behavior Change: An Empirical Analysis (2nd ed.,

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14 Page 14 of 14 Table 4. Table 5.