Psychological Versus Pharmacological Treatments of Bulimia Nervosa Predictors and Processes of Change

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1 Page 1 of 16 Journal of Consulting and Clinical Psychology August 1999 Vol. 67, No. 4, by the American Psychological Association For personal use only--not for distribution. Psychological Versus Pharmacological Treatments of Bulimia Nervosa Predictors and Processes of Change G. Terence Wilson Eating Disorders Clinic, Rutgers The State University of New Jersey Katharine L. Loeb Eating Disorders Clinic, Rutgers The State University of New Jersey B. Timothy Walsh New York State Psychiatric Institute Columbia University Erich Labouvie Center for Alcohol Studies, Rutgers The State University of New Jersey Eva Petkova New York State Psychiatric Institute Columbia University Xinhua Liu New York State Psychiatric Institute Columbia University Christine Waternaux New York State Psychiatric Institute Columbia University ABSTRACT This article extends the acute outcome findings from a study comparing psychological and pharmacological interventions for bulimia nervosa ( B. T. Walsh et al., 1997 ) by examining 3 additional domains: predictive factors, therapeutic alliance, and time course of change. One hundred twenty women were randomized to cognitive behavioral therapy (CBT), supportive psychotherapy (SPT) plus antidepressant medication or a placebo, or a medication-alone condition. Results indicate that high baseline frequencies of binge eating and vomiting, as well as a positive history of substance abuse or dependence, are negative prognostic indicators. Although a greater overall therapeutic alliance may increase the likelihood of remission, symptom change over the course of treatment may have as much of an impact on patient ratings of alliance as the reverse. CBT was significantly more rapid than SPT in reducing binge eating and vomiting frequencies. Correspondence may be addressed to G. Terence Wilson, Eating Disorders Clinic, Rutgers, The State University of New Jersey, 41C Gordon Road, Piscataway, New Jersey, Electronic mail may be sent to tewilson@rci.rutgers.edu Received: June 9, 1998 Revised: November 6, 1998 Accepted: November 10, 1998 Antidepressant medication and cognitive behavioral therapy (CBT) have been the two most intensively studied treatments of bulimia nervosa ( Wilson & Fairburn, 1998 ). Antidepressant drugs have consistently proved statistically superior to a pill placebo in reducing binge eating and purging in numerous randomized

2 Page 2 of 16 control trials ( Devlin & Walsh, 1995 ). Different classes of antidepressants appear to be equally effective. However, two uncontrolled studies have suggested that patients who fail to respond to an initial antidepressant drug may respond to another ( Mitchell et al., 1989 ; Walsh, Hadigan, Devlin, Gladis, & Roose, 1991 ). Controlled studies have shown that CBT is more effective than credible comparison treatments that control for the nonspecifics of therapy and superior to behavioral versions of the treatment that omit the explicit focus on modifying attitudes toward body shape and weight ( Fairburn, Jones, Peveler, Hope, & O'Conner, 1993 ). CBT is significantly more effective than, or at least as effective as, any form of psychotherapy with which it has been compared ( Fairburn et al., 1993 ; Garner et al., 1993 ). In direct comparisons, CBT seems to be superior to treatment with a single antidepressant drug ( Agras et al., 1992 ). Combining CBT with antidepressant medication is significantly more effective than medication alone ( Agras et al., 1992 ; Leitenberg et al., 1994 ; Mitchell et al., 1990 ). In contrast, combining CBT and antidepressant medication produces few consistent benefits over CBT alone. However, Agras et al. found that the combination might have a synergistic effect that could be superior to CBT alone on some measures. The combination of CBT and antidepressant medication has been shown to be more effective than CBT alone in reducing depression and anxiety ( Mitchell et al., 1990 ). We completed a study in which we (a) compared the efficacy of CBT with that of psychodynamically oriented supportive psychotherapy (SPT), (b) compared a novel two-stage antidepressant medication treatment with a pill placebo, and (c) evaluated whether a combination of antidepressant medication plus psychological treatment was more effective than medication only. The acute outcome data are reported elsewhere ( Walsh et al., 1997 ). To summarize, CBT was superior to SPT in reducing the frequency of binge eating and vomiting. Patients receiving active medication in combination with psychological treatment experienced greater improvement in binge eating and depression than did patients receiving a placebo and psychological treatment. CBT plus active medication was superior to medication alone, whereas SPT plus active medication was not. In this article, we focus on predictors, processes, and time course of change. No reliable predictors of response either to CBT or to antidepressant medication have been identified ( Wilson & Fairburn, 1998 ). Some studies have found that the lower the patients' previous lowest weight, the worse the outcome with CBT ( Fahy & Russell, 1993 ; Wilson, Rossiter, Kleifield, & Lindholm, 1986 ). Agras, Dorian, Kirkley, Arnow, and Bachman (1987) reported the same finding with imipramine treatment. However, Fairburn et al. (1993) obtained no effect of previous low weight on the effects of CBT. Blouin et al. (1994) found that patients with lower past and present weights showed greater reductions in vomiting frequency. Comorbid personality disorders have been shown to be a negative predictor for both CBT ( Fahy, Eisler, & Russell, 1993 ) and antidepressant medication ( Rossiter, Agras, Telch, & Schneider, 1993 ). However, even here contradictory findings exist ( Ames-Frankel et al., 1992 ; Davis, Olmsted, & Rockert, 1992 ). The therapeutic alliance has been hypothesized to be an important process variable in treatment outcome research. Data indicate that it is a common factor across different forms of psychotherapy and even pharmacological treatment ( Krupnick et al., 1996 ). It is often argued that the therapeutic alliance accounts for more of the variance in outcome than specific treatment methods ( Beitman, Goldfreid, & Norcross, 1989 ). The present study is the first to compare levels of therapeutic alliance and their relationship to treatment outcome for CBT and pharmacological therapy for bulimia nervosa. Time course of change during treatment has both theoretical and practical significance. At the theoretical level, different time courses of improvement between treatments suggest that they are mediated by different

3 Page 3 of 16 mechanisms of action ( Fairburn et al., 1993 ). CBT should exert its effects by changing eating behavior and attitudes directly; other changes would be secondary. SPT is hypothesized to work indirectly with progressive but delayed effects on eating disorder symptoms such as binge eating and vomiting. From a practical viewpoint, speed of action is an important element of evaluating treatment outcome. Antidepressant medication exerts its effect rapidly ( Devlin & Walsh, 1995 ). CBT is also comparatively quick acting ( Wilson & Fairburn, 1998 ), producing more rapid improvement than supportive expressive psychotherapy ( Garner et al., 1993 ), stress management therapy ( Laessle et al., 1991 ), and interpersonal psychotherapy (IPT; Fairburn et al., 1993 ). Analysis of the time course of treatment effects is important also in another respect. Early response to treatment might prove to be a useful predictor of therapy outcome. Given the lack of reliable predictors of treatment outcome across different clinical disorders, patients' early response to treatment itself has been proposed as an alternative predictor of outcome ( Mathews et al., 1976 ). Analysis of time course may answer the important clinical question of whether therapists can determine when patients who have not improved will be unlikely to respond to more of the same treatment. In their analysis of pharmacological treatment of depression, Quitkin et al. (1996) determined the point until which patients receiving active medication were more likely to be responders at the end of treatment than patients receiving a pill placebo. A similar model might apply to manual-based CBT. For example, studies of CBT for depression show that 60% to 80% of improvement occurs as early as Week 4 ( Ilardi & Craighead, 1994 ). Fennell and Teasdale (1987) found that patients who did not respond (at least 50% reduction in depression) by the end of the first 2 weeks of psychological treatment fared very poorly at posttreatment and over a 1-year follow-up. In the treatment of bulimia nervosa, Jones, Peveler, Hope, and Fairburn (1993) showed that CBT produced reductions in binge eating and purging until Week 8 of their 18-week treatment, after which there was little change. The practical implication of these findings is that if, after an identifiable number of sessions, a patient has not improved at least to some degree with CBT, treatment should be changed. However, this model would not apply to a psychotherapy like SPT with its predicted slower time course ( Wilson, 1998 ). Design Method Patients were women between the ages of 18 and 45 years who met Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev.; DSM III R ; American Psychiatric Association, 1987 ) criteria for bulimia nervosa for at least 1 year. Individuals who were deemed eligible for the study through a telephone screening were invited for an evaluation interview in which eating disorder psychopathology and other Axis 1 disorders were assessed ( n = 209). Respondents who appeared to meet entry criteria were asked to attend a second appointment 1 week later in which a psychiatrist took a medical history and conducted a physical exam ( n = 149). Eligible patients then entered a single-blind placebo washout phase lasting 7 to 10 days. Those who continued to meet entry criteria ( n = 120) were randomly assigned to one of five treatments as shown in Table 1. Treatments Both psychological treatments were conducted on an individual, outpatient basis for a total of 20 sessions over a 4-month period. CBT.

4 Page 4 of 16 This treatment was based on a manual ( Wilson, 1989 ) derived from the treatment approach of Fairburn, Kirk, O'Conner, and Cooper (1986 ). Stage 1 (Sessions 1 8) comprised the following: an explanation of the philosophy and goals of the treatment, daily self-monitoring of eating to identify high-risk situations for binge eating and purging, education about weight regulation and how dieting is linked to binge eating, cognitive restructuring, and instruction and guidance in learning to normalize eating patterns. Stage 2 (Sessions 9 16) consisted of problem solving for coping with high-risk situations for binge eating and purging, an emphasis on more flexible eating patterns and consumption of previously avoided foods, and cognitive restructuring focused on specific concerns about body shape and weight. Stage 3 (Sessions 17 20) was devoted mainly to relapseprevention training. SPT. This treatment was a manual-based, modified version of the short-term psychotherapy used in the Fairburn et al. (1986) study. SPT differed from Fairburn et al.'s method in at least two important respects: (a) It did not include self-monitoring of eating and (b) it was less directive and focal in nature. SPT in the present study was designed to control for nonspecific therapeutic influences inherent in CBT. In contrast to CBT, SPT was nondirective and emphasized patient self-exploration and understanding. No attempt was made to modify eating disorder symptoms directly. In parallel with CBT, there were three stages. Stage 1 (Sessions 1 8) included a detailed history of the development of bulimia nervosa, a personal and family history, and a focus on putative underlying problems that might be responsible for the eating disorder. In Stage 2 (Sessions 9 16) therapists encouraged patients to explore underlying emotional issues and facilitated expression of feelings. Stage 3 focused on termination issues. Medication. Patients first received desipramine for 8 weeks ( mg/day). If binge frequency had not declined by at least 75% or if intolerable side effects occurred, the desipramine was tapered and discontinued over the succeeding 2 weeks and patients then received fluoxetine (60 mg/day). Patients randomly assigned to the placebo condition first received a desipramine placebo and, following the same criteria, were then given a fluoxetine placebo. Patients met weekly with a psychiatrist who assessed medication response and side effects, provided basic education concerning medical aspects of eating disorders, and supported whatever attempts the patient was making to improve without specifically endorsing any particular approach. Therapists One male and two female therapists administered both CBT and SPT. One was a psychiatrist, one a licensed clinical psychologist, and one a licensed social worker obtaining a doctoral degree in clinical psychology. Therapists received biweekly group supervision from experts in each modality, and supervisors regularly reviewed and critiqued randomly selected audiotaped sessions. Two psychiatrists administered treatment within the medication-only condition. Assessment Patients recorded the number of daily binge eating and vomiting episodes in a diary that was collected each week. Eating disorder psychopathology was assessed using the Eating Disorder Examination (EDE; Fairburn

5 Page 5 of 16 & Cooper, 1993 ), which yields subscales that assess the severity of dietary restraint, concern about eating, concern about shape, and concern about weight over the previous 4 weeks. Patients were also asked to complete the following self-report questionnaires at pretreatment, at specified intervals during the study, and at termination: the Body Shape Questionnaire (BSQ; Cooper, Taylor, Cooper, & Fairburn, 1987 ), the Beck Depression Inventory (BDI; Beck, Ward, Mendelson, Mock, & Erbaugh, 1961 ), the Symptom Checklist 90 (SCL-90; Derogatis, 1977 ), and a visual analog scale to rate the treatments' logic and relevance. The Helping Relationship Questionnaire (HRQ; Luborsky, 1984 ), a patient-rated measure of therapeutic alliance, was obtained at Session 5, at Session 12, and at termination (Session 20). The HRQ measures two main aspects of the therapeutic relationship: (a) the experience of being understood and receiving a helpful attitude and (b) the experience of being involved in a collaborative effort with the therapist. It has predicted treatment outcome in focal psychotherapy ( Luborsky, McLellen, Diguer, Woody, & Seligman, 1997 ) and was used in the present study to assess the quality and relative contributions to treatment outcome of the therapist patient relationship across the different therapies. In cases of premature termination when patients complied with a final evaluation, the HRQ from this last session was used, provided that the visit occurred past Session 12. This questionnaire was submitted by patients directly to research assistants, not therapists, to minimize the possibility of biased ratings. The presence of Axis I disorders was assessed using the Structured Clinical Interview for DSM III R ( Spitzer, Williams, & Gibbon, 1987 ). Statistical Analyses A p value of.05 was used as the standard for statistical significance for all analyses. The statistical strategies used to study predictor variables, the role of the therapeutic alliance, and time course during treatment are described in their respective sections below. Predictor Variables Results Fifteen pretreatment variables were considered for status as factors predictive of outcome in this study: weekly binge eating and vomiting frequencies as obtained by patient diaries; EDE Restraint, Shape Concern, and Weight Concern subscale scores; BSQ score; age; body mass index (BMI); duration of bulimia nervosa; history of anorexia nervosa; patients' baseline ratings of the degree to which they viewed their assigned treatment as "logical" and "relevant"; the Global Symptom Index (GSI) of the SCL-90; past or present mood disorder (major depression or dysthymia); and a history of alcohol or drug abuse or dependence. These variables were subjected to a principal-component analysis, which yielded a six-factor solution. For each factor, loadings greater than.50 were considered significant. Factor 1, the Shape Weight factor, included the BSQ (.81), the EDE Shape Concern (.91) and Weight Concern (.82) subscales, and the BMI (.54). The mean of these four variables, adjusted for discrepant standard deviations, was later entered as the representative variable for this factor. Factor 2, the Duration of Bulimia Nervosa factor, included duration of bulimia nervosa (.92) and age (.92), the former of which was used as the representative variable for this factor. Factor 3, The Attitude Toward Treatment factor, included the patients' baseline ratings of the degree to which they viewed their assigned treatment as logical (.93) and relevant (.93). The mean of these two variables was later entered as the predictor corresponding to this factor. Factor 4, the Binge Vomit factor, included baseline binge eating (.81) and vomiting (.84) frequencies. The mean of these two variables,

6 Page 6 of 16 adjusted for differences in standard deviation, was entered as the covariate for the analyses described below. Factor 5, the General Psychopathology factor, included history of mood disorder (.60) and the GSI (.77). Factor 6 had no cohesive pattern. The variables that did not load on Factors 1 5, the EDE Restraint subscale, history of anorexia nervosa, and history of substance abuse, were entered individually as predictors. For the purposes of this set of analyses, we defined outcome in three ways: (a) completion of treatment, (b) presence or absence of remission from binge eating and vomiting within the last 2 weeks of treatment, and (c) the sum of weekly binge eating and vomiting frequencies derived from the patient's self-monitoring over the last 2 weeks of treatment. We performed logistic regression analyses with the two dichotomous outcome variables (remission and completion of treatment) and regression analyses with the continuous measure of outcome (termination frequencies). Backward stepwise elimination procedures were applied. Three treatment contrasts (CBT vs. SPT, medication vs. placebo, and medication only vs. therapy plus medication) were entered as covariates along with the Binge Vomit factor. Completion of treatment. The greater a patient at Session 1 rated her assigned treatment as logical and relevant, the more she was likely to remain in the study ( p =.04, odds ratio [OR] = 1.02, 95% confidence interval [CI] = ]). The ORs of the nonsignificant predictors ranged from 0.45 to The largest nonsignificant OR (2.48) was found for history of anorexia nervosa, in a counterintuitive direction: A positive history was (nonsignificantly) associated with an increased likelihood of completion of treatment ( p =.12) Remission. Only therapy assignment emerged as a significant predictor of outcome, with CBT increasing the likelihood of remission ( p =.02, OR = 4.81, 95% CI = ). In addition, there was a trend for the Binge Vomit factor to predict remission ( p =.06, OR = 0.94), with higher frequencies decreasing the chance of remission. The ORs of the nonsignificant predictors ranged from 0.24 to End-of-treatment binge eating plus vomiting frequencies. The Binge Vomit factor ( p =.0001), therapy assignment ( p =.02, favoring CBT), positive history of anorexia nervosa ( p =.05), and positive history of substance abuse ( p =.04) were all significantly associated with outcome in the expected directions. The nonsignificant predictors accounted for only 0.04% of the total variance, cumulatively. The Role of the Therapeutic Alliance The medication-only cell was excluded from these analyses. There were three reasons for this: (a) One psychiatrist administered treatment exclusively within this cell, a design issue that would confound any treatment-condition differences with psychiatrist differences; (b) there was less psychiatrist patient contact in this cell than there was therapist patient contact in the other conditions, which is another confound; and (c) the course of the medication-only treatment differed from the others because patients who could not tolerate desipramine during the first medication phase were accelerated to Session 14 to begin fluoxetine. Thus, 92 participants, each assigned to one of three therapists, were included here. As in the previous analyses, outcome was defined in three ways: completion of treatment, remission, and binge eating plus vomiting frequency at termination. The analyses (regression or logistic regression) that we used were also

7 Page 7 of 16 conducted as above, unless otherwise noted. We initially conducted a set of analyses to determine whether any therapist main effects or Therapist Treatment interaction effects were present. We used logistic regressions to model dropout and remission status as functions of psychological treatment (two levels) and therapist (three levels) and their interaction; we used a 2 3 analysis of covariance for termination binge eating plus vomiting frequency as a dependent measure. In addition, we conducted a 2 3 analysis of variance (ANOVA) with overall therapeutic alliance (the mean HRQ score of the three assessment points) as the dependent variable. The second question that we addressed was whether the therapeutic alliance differed among the interventions early in treatment (Session 5), midway through treatment (Session 12), at the end of treatment, or overall (the mean HRQ score of the three time points). Three effects were examined: psychological treatment assignment, medication assignment, and their interaction. The third question was whether our measure of the therapeutic alliance predicted outcome, either in the overall sample or differentially by treatment assignment. For these analyses, mean HRQ score was entered as the predictor. The fourth issue addressed was the temporal relationship between symptom change and level of therapeutic relationship; that is, at each assessment point, was the therapeutic alliance predicted by prior symptom change or predictive of subsequent symptom change ( DeRubeis & Feeley, 1990 )? For this question, dropout and remission status were not applicable, as they are variables established only at termination. Symptom change scores were computed at the three HRQ assessment points. Symptom change scores represent the residuals from regressing either (a) the change in binge eating plus vomiting frequencies that occurred by the present session on the baseline frequencies (for prior change) or (b) the change from the present session to termination on the current frequency (for subsequent change). At Sessions 5 and 12, both prior and subsequent change scores were derived. At termination, only prior symptom change was analyzed. The five change scores were each correlated with the HRQ score corresponding to the relevant time point. This was done for the overall sample of patients receiving psychotherapy and by treatment assignment (CBT vs. SPT and medication vs. placebo). Question 1: Were therapist effects present? There were no significant main effects of therapist for the three outcome measures or for mean HRQ score. The Treatment Therapist interaction terms were also not significant, indicating that therapists were equally effective in administering the different treatments and maintained similar levels of therapeutic alliance in CBT and SPT. Question 2: Did the treatments differ on the HRQ? There were no significant differences in HRQ score between treatments at Session 5 or at termination. At Session 12, a significant Therapy Medication effect was found, F (1, 72) = 4.80, p =.03; for SPT, the therapeutic alliance was higher with medication than without. CBT exhibited the opposite pattern, with alliance being higher in the placebo cell. There were no significant differences in overall alliance (mean HRQ across the three time points) between treatments. Table 2 displays the overall alliance scores by randomization. Question 3: Did the HRQ predict outcome? The only significant finding was that mean HRQ score predicted remission status in the overall sample ( p =.03), with greater alliance increasing the likelihood of remission. Although alliance did not significantly

8 Page 8 of 16 predict binge eating and vomiting frequencies as the outcome variable, treatment condition did. Of note are the corresponding squared semipartial correlations, which indicate each factor's unique contribution to the overall variance: for mean HRQ, 2%; for psychotherapy assignment, 6%; and for medication assignment, 4%. Question 4: What was the temporal relationship between HRQ scores and symptom change? In the overall sample, prior symptom change predicted HRQ score at Session 12 ( r =.22, p =.05). No relationship was found between HRQ score and prior or subsequent symptom change in the CBT or SPT conditions when examined separately. In the active-medication cells, alliance predicted subsequent symptom change at Session 5 ( r =.34, p =.04) but was predicted by prior symptom change at termination ( r =.39, p =.02). In the placebo condition, prior symptom change predicted HRQ score at Session 12 ( r =.31, p =.05). Time Course We investigated time course changes with two different approaches. The medication-only cell was excluded from these analyses because patients in this condition were accelerated to Session 14 if they experienced intolerable side effects to desipramine during the first medication phase, rendering their time course unique. Survival analyses were used to identify the speed of action of the different therapies. For these analyses, the event was improvement, defined as a 75% reduction in baseline binge eating and vomiting for a minimum of 2 weeks, which was then sustained until the end of the trial or until the patient dropped out. We decided a priori to study the effect of three theoretically relevant baseline covariates: body shape concern, dietary restraint, and depression. Each covariate was dichotomized using a median split: for the BSQ, less than or equal to 140 or greater than 140; for the EDE Restraint subscale, less than or equal to 3.2 or greater than 3.2; and for the BDI, less than or equal to 20 or greater than 20. We assessed the effect of each of the covariates with Cox proportional hazards modeling, which included psychological therapy and medication. We studied the effect of the covariates on the time to response by fitting the most complex model containing the three-way interaction Therapy Medication Covariate and successively eliminating the nonsignificant terms (backward elimination). Second, for a more fine-grained but exploratory analysis of change during treatment, we examined only those patients who had either completed all assessments at the scheduled intervals or those patients who had missed few enough assessments (three or fewer) to justify imputing those data points. Data imputation was accomplished by applying the mean of the surrounding data points. As with the survival analyses, patients who received medication alone were excluded. The resulting sample consisted of 67 patients, or 73% of the original sample size of 92 patients. We compared this group of completers with the remainder of the patient sample using t tests to determine if there were any pre- or posttreatment differences on the following variables: binge eating and vomiting frequencies, the BSQ, the BDI, the GSI, and the BMI. We then conducted polynomial repeated measures ANOVAs assessing psychotherapy and medication effects on both weekly binge eating and vomiting frequencies. Pretreatment (evaluation) binge eating and vomiting frequencies were entered as covariates for these analyses. Survival analyses. For vomiting, there were significant main effects favoring CBT and medication. The hazard ratio for CBT versus SPT was 4.73 (95% CI = ); for active medication versus pill placebo, the hazard ratio was 2.01 (95% CI = ). Figure 1 presents the Kaplan-Meier survival curves for the different

9 Page 9 of 16 treatments. There was no interaction between psychological therapy and medication. The hazard ratio for CBT plus medication versus CBT plus pill placebo was the same as the overall hazard ratio for medication versus placebo (i.e., 2.01, 95% CI = ). For binge eating, the only main effect was CBT versus SPT, with a hazard ratio of 1.88 (95% CI = ). Time to remission on medication did not differ significantly from time to remission on the pill placebo. There were significant interactions between psychological treatment and level of depression, as well as medication and level of depression, in their effect on the time to 75% sustained reduction of baseline vomiting frequencies. The effects of both psychological therapy and medication were different depending on the baseline BDI scores (see Figure 2 ). The hazard ratio for active medication versus placebo was 1.22 (95% CI = ) for low BDI scores but 6.79 (95% CI = ) for high BDI scores. The comparable scores for CBT versus SPT were 2.91 (95% CI = ) and (95% CI = ), respectively. The pattern for binge eating was different. There were significant interactions between psychological therapy and both BSQ and EDE Restraint scores but not between psychological therapy and BDI scores; on the first two measures, the greater the severity at baseline, the less the superiority of CBT versus SPT. The hazard ratio for response on CBT versus SPT was 3.54 (95% CI = ) with BSQ less than 140 and only 1.04 (95% CI = ) with BSQ greater than 140. On dietary restraint, the hazard ratio was 3.37 (95% CI = ) for lower EDE Restraint scores but only 1.12 (95% CI = ) for higher EDE Restraint scores. Repeated measures ANOVAs. Sixty-four of the 2,144 data points (3%) were imputed. No statistically significant differences were found between patients included in these analyses and those with four or more missing data points during the course of treatment on baseline levels of binge eating and vomiting. For binge eating, a quadratic trend significantly favored CBT over SPT, F (1, 63) = 4.04, p =.05, indicating that CBT produced a more rapid reduction initially than did SPT. There were no time-course differences between medication and placebo. Between-subjects main effects were found for psychotherapy in the binge eating analyses, F (1, 63) = 9.56, p =.003, with CBT emerging as superior to SPT, and for both psychotherapy, F (1, 63) = 10.28, p =.002, and medication, F (1, 63) = 4.63, p =.04, in the vomiting analyses. Inspection of data revealed that CBT produced much of its effect by Session 5. Seventy-six percent of CBT-produced posttreatment improvement in binge eating frequency and 69% of CBT improvement in vomiting was evident by Week 3. To further explore the nature of this early response to treatment, we conducted two additional sets of polynomial repeated measures ANOVAs for binge eating and vomiting. In the first set, we analyzed the changes from Session 1 to Session 5 (Weeks 1 3), exploring both psychotherapy and medication effects. The second set of ANOVAs examined improvement rates from Session 7 to Session 20 (Weeks 4 16). In addition to comparing treatment conditions, these analyses divided patients on the basis of their symptom status at Week 3. Patients whose frequencies were improved 50% or greater were considered early responders. Interaction terms were included to investigate the relationship between treatment condition and response status. Significant linear effects for Time Therapy Assignment were found within the early phase of treatment (Weeks 1 3) for both binge eating, F (1, 63) = 11.20, p =.001, and vomiting, F (1, 63) = 8.24, p =.006. These results favored CBT over SPT. In addition, a linear effect for Time Medication Status was found for vomiting, F (1, 63) = 4.51, p =.04, with active medication emerging as superior to, or faster than, the placebo. Between-subjects effects were not significant in these early weeks.

10 Page 10 of 16 Twenty-three (72%) of the 32 patients who received CBT were designated early responders on the basis of their binge eating frequency; the same number of patients had decreased their vomiting frequency by at least 50% by the 3rd week of treatment. For SPT, 11 of the 35 patients (31%) met the binge eating response criterion and 10 (29%) met the vomiting response criterion. Twenty of the 32 (63%) patients assigned to the active-medication condition responded early in terms of binge eating improvement, and 19 (59%) improved early in terms of vomiting frequency. For the placebo co standard and the same number met the vomiting criterion. Within the second phase of treatment, significant linear effects for Time Improvement were found for binge eating, F (1, 60) = 4.61, p =.04, and for Time Therapy Improvement for both binge eating, F (1, 60) = 4.97, p =.03, and vomiting, F (1, 60) = 12.06, p =.001. In addition, a cubic effect for Time Medication Assignment was found for binge eating, F (1, 60) = 4.92, p =.03, and a quadratic effect for Time Medication Status was found for vomiting, F (1, 60) = 4.97, p =.03. Figure 3 shows that within CBT, early responders remained superior to the other patients over the course of treatment. In contrast, within SPT, the improvement of early responders deteriorated. For CBT, 61% of the patients classified as "rapid" responders on the measure of binge eating and 22% classified as "slow" responders achieved remission in terms of binge eating at posttreatment. For vomiting, the corresponding percentages were 61% and 11%, respectively. The comparable figures for SPT were 27% and 29%, respectively, for binge eating and 30% and 20%, respectively, for vomiting. For active medication, 60% of the participants categorized as rapid responders on the measure of binge eating and 33% categorized as slow responders achieved remission in terms of binge eating at posttreatment. Discussion Among patients with bulimia nervosa, higher frequencies of binge eating and vomiting and a positive history of substance abuse or dependence appear to predict a poor response to treatment. Patients' initial view of therapy as relevant to their particular problems may increase the likelihood that they will remain in treatment. Previous research has yielded inconsistent findings regarding these predictor variables. Garner et al. (1990) reported that pretreatment binge eating frequency, but not purging frequency, was related to treatment outcome: the higher the frequency, the worse the outcome. Conversely, Davis et al. (1992) found that a higher frequency of vomiting, but not binge eating, predicted poor outcome. Previous studies have not found a history of substance abuse to be a negative predictor of response to treatment ( Mitchell, Pyle, Eckert, Hatsukami, & Soll, 1990 ; Strasser, Pike, & Walsh, 1992 ). Most importantly, the results did not reveal any treatment-specific predictor variables that would permit matching of patients to either CBT or antidepressant medication. A limitation of the present study was the lack of measures of Axis II personality disorders that have been shown to predict a poorer response to therapy ( Rossiter et al., 1993 ). Identifying reliable predictors of response to specific treatments will require much larger sample sizes than that of the present study and the other even smaller scale studies in the research literature. Patients' ratings of the therapeutic alliance were a positive predictor of remission within the overall sample. No interaction was found between HRQ scores and treatment condition, indicating that this relationship did not differ across therapies. Thus, contrary to Carroll, Nich, and Rounsaville's (1997) findings with cocaine addicts, the therapeutic alliance did not exert a greater influence on outcome in a relatively unstructured control therapy (SPT) than in a highly specific psychological intervention like CBT. Krupnick et al.'s (1996) analyses of the National Institute of Mental Health (NIMH) Treatment of Depression Collaborative

11 Page 11 of 16 Research Program (TDCRP; Elkin et al., 1989 ) showed that the therapeutic alliance accounted for more of the variance in response to treatment than the specific therapies, which were not significantly related to outcome. Results like these are often put forward in support of the claim that the therapeutic relationship is more important than particular treatments that are essentially equivalent in their effects ( Beitman et al., 1989 ). The present findings suggest otherwise. The specific therapies were significantly related to outcome and accounted for more of the variance than the therapeutic alliance, which contributed only 2%. This is consistent with our overall finding that CBT was significantly more effective than SPT ( Walsh et al., 1997 ). Unlike our study, the psychological treatments in the NIMH TDCRP did not differ from each other. Importantly, the present study revealed no overall differences between CBT and SPT in patients' ratings on the HRQ. This strengthens the conclusion that the superiority of CBT over SPT can be attributed to factors specific to the treatment itself. Significant positive correlations between measures of the therapeutic alliance and treatment outcome are often interpreted as evidence of the predictive if not causal properties of the former. In the present study, analysis of the temporal relationship between these two variables showed that, if anything, it was prior symptom change that more consistently influenced patient ratings of the therapeutic alliance than vice versa. This is similar to findings from the treatment of depression using CBT ( DeRubeis & Feeley, 1990 ). A consistent finding was that CBT was significantly more rapid than SPT in reducing binge eating and vomiting frequencies over the course of treatment. The survival analyses showed significant main effects for CBT versus SPT for both vomiting and binge eating. The repeated measures analysis of treatment completers showed that CBT was significantly more rapid in its effect than SPT on both binge eating and vomiting. Using a similar analysis only of completers, Jones et al. (1993) also reported the same pattern of results for binge eating and vomiting frequencies. Taken in conjunction with the end-point analyses reported in our previous article, in which CBT was significantly more effective than SPT on both the 2-week selfmonitoring and 4-week EDE measures of binge eating and vomiting ( Walsh et al., 1997 ), it is safe to conclude that CBT is faster and more effective than SPT in the treatment of bulimia nervosa. CBT's impact on vomiting was influenced by patients' pretreatment level of depression. The more depressed the patients, the more rapid the effect of CBT versus SPT. This difference could be interpreted as showing the greater efficacy of CBT relative to SPT among patients with more severe psychopathology. However, the interactions between CBT and pretreatment levels of shape and weight concerns suggest the opposite. The more severe these features of the core psychopathology of bulimia nervosa, the less the relative superiority of CBT over SPT. However, these results must be interpreted cautiously. They are not obtained with vomiting as the measure of outcome and need to be replicated before we can view them with confidence. Findings on the time course for antidepressant medication versus pill placebo are less robust. The two conditions did not differ in the completer analysis, possibly because of the reduced sample size. The survival analysis of time to response showed a significantly more rapid effect of medication versus placebo on vomiting but not binge eating. As in the case of CBT, the effect of antidepressant medication was moderated by patients' level of depression. Antidepressant medication was superior to the pill placebo only among the more depressed patients. Baseline levels of depression have not predicted the effects of antidepressant medication in prior studies ( Devlin & Walsh, 1995 ). Nonetheless, given the well-established antidepressant effect of the two drugs used in this study, the finding that the medication was most efficient in those patients with high BDI scores makes clinical sense. As in research on CBT for the treatment of depression ( Ilardi & Craighead, 1994 ), CBT in the present

12 Page 12 of 16 study had a rapid effect on binge eating and vomiting. By Session 5, CBT was significantly superior to SPT and remained so over the full course of treatment. Following Fennell and Teasdale's (1987) analysis of time course of CBT for depression, we divided patients who had received CBT or SPT into rapid versus slow responders on the basis of whether or not they showed a 50% or more reduction in binge eating and vomiting by Session 5. Consistent with Fennell and Teasdale's findings, our rapid CBT responders tended to continue to do better on average over the full course of therapy than the slow responders (see Figure 3 ). In contrast, the improvement of rapid SPT responders tended to deteriorate over the course of treatment in similar fashion to Fennell and Teasdale's control group's improvement. We speculate that the initial response to SPT was akin to a placebo effect that then dissipated over time. Jones et al. (1993) found that both CBT and IPT produced an immediate reduction in binge eating and purging in the first few sessions, with only participants in the CBT condition continuing to improve beyond that initial change. Although results from the present study show continuing differences between rapid and slow responders to CBT, they do not provide clear guidance about when to decide that the treatment is ineffective for a particular patient. For example, 22% of the slow responders receiving CBT had ceased binge eating at posttreatment and 11% had stopped vomiting. Thus, at least some slow responders can benefit substantially from continuing with the full course of CBT. Nevertheless, future studies using larger sample sizes might well explore this question of when to decide that the patient will not respond to treatment. It might be that a later session would provide a more discriminating but still time-saving decision point. Finally, future research might usefully focus on examining who are these early responders to CBT and what it is during the first few sessions that sets them apart from patients who respond more slowly. In the treatment of depression, Fennell and Teasdale (1987) and Ilardi and Craighead (1994) pointed to the value of early compliance with homework assignments as providing immediate positive feedback about the feasibility of change. Identifying putative mechanisms of change such as these would not only help explain the early response to treatment of some patients but might also suggest means to improve CBT for all patients. References Agras, W. S., Dorian, B., Kirkley, B. G., Arnow, B. & Bachman, J. (1987). Imipramine in the treatment of bulimia: A double-blind controlled study. International Journalof Eating Disorders, 6, Agras, W. S., Rossiter, E. M., Arnow, B., Schneider, J. A., Telch, C. F., Raeburn, S. D., Bruce, B., Perl, M. & Koran, L. M. (1992). Pharmacologic and cognitive behavioral treatment for bulimia nervosa: A controlled comparison. American Journal of Psychiatry, 149, American Psychiatric Association. (1987). Diagnostic and statistical manual of mental disorders ((3rd ed., rev.).washington, DC: Author.) Ames-Frankel, J., Devlin, M. J., Walsh, B. T., Strasser, T. J., Sadik, C., Oldham, J. & Roose, S. P. (1992). Personality disorder diagnoses in patients with bulimia nervosa: Clinical correlates and changes with treatment. Journalof Clinical Psychiatry, 53, Beck, A. T., Ward, C. H., Mendelson, M., Mock, J. & Erbaugh, J. (1961). An inventory for measuring depression. Archives of General Psychiatry, 4, Beitman, B. D., Goldfried, M. R. & Norcross, J. C. (1989). The movement toward integrating the psychotherapies: An overview. American Journal of Psychiatry, 146, Blouin, J. H., Carter, J., Blouin, A. G., Tener, L., Schnare-Hayes, K., Zuro, C., Barlow, J. & Perez, E. (1994). Prognostic indicators in bulimia nervosa treated with cognitive behavioral group therapy. International Journal ofeating Disorders, 15,

13 Page 13 of 16 Carroll, K. M., Nich, C. & Rounsaville, B. J. (1997). Contribution of the therapeutic alliance to outcome in active versus control psychotherapies. Journal of Consulting andclinical Psychology, 65, Cooper, P. J., Taylor, M. J., Cooper, Z. & Fairburn, C. G. (1987). The development and validation of the Body Shape Questionnaire. International Journal of EatingDisorders, 6, Davis, R., Olmsted, M. P. & Rockert, W. (1992). Brief group psychoeducation for bulimia nervosa: II. Prediction of clinical outcome. International Journal of Eating Disorders, 11, Derogatis, L. R. (1977). SCL-90-R: Administration, scoring and procedures manual for the revised version. (Baltimore: Johns Hopkins School of Medicine) DeRubeis, R. J. & Feeley, M. (1990). Determinants of change in cognitive therapy for depression. Cognitive Therapy andresearch, 14, Devlin, M. J. & Walsh, T. (1995). Medication treatment for eating disorders. Journal of Mental Health, 4, Elkin, I., Shea, T., Watkins, J. T., Imber, S. D., Sotsky, S. M., Collins, J. F., Glass, D. R., Pilkonis, P. A., Leber, W. R., Docherty, J. P., Fiester, S. J. & Parloff, M. B. (1989). National Institute of Mental Health Treatment of Depression Collaborative Research Program: General effectiveness of treatments. Archives of General Psychiatry, 46, Fahy, T. A., Eisler, I. & Russell, G. F. M. (1993). A placebo-controlled trial of d-fenfluramine in bulimia nervosa. British Journal of Psychiatry, 162, Fahy, T. A. & Russell, G. F. M. (1993). Outcome and prognostic variables in bulimia nervosa. International Journal of Eating Disorders, 14, Fairburn, C. G. & Cooper, P. J. (1993). The Eating Disorder Examination.(In C. G. Fairburn & G. T. Wilson(Eds.), Binge eating: Nature, assessment, and treatment (pp ). New York: Guilford Press.) Fairburn, C. G., Jones, R., Peveler, R. C., Hope, R. A. & O'Connor, M. (1993). Three psychological treatments for bulimia nervosa: A comparative trial. Archives of GeneralPsychiatry, 48, Fairburn, C. G., Kirk, J., O'Connor, M. & Cooper, P. J. (1986). A comparison of two psychological treatments for bulimia nervosa. Behaviour Research and Therapy, 24, Fennell, M. J. V. & Teasdale, J. D. (1987). Cognitive therapy for depression: Individual differences and the process of change. Cognitive Therapy and Research, 11, Garner, D. M., Olmsted, M. P., Davis, R., Rockert, W., Goldbloom, D. & Eagle, M. (1990). The association between bulimic symptoms and reported psychopathology. International Journal ofeating Disorders, 9, Garner, D. M., Rockert, W., Davis, R., Garner, M. V., Olmsted, M. P. & Eagle, M. (1993). Comparison of cognitive behavioral and supportive expressive therapy for bulimia nervosa. American Journal of Psychiatry, 150, Ilardi, S. S. & Craighead, W. E. (1994). The role of nonspecific factors in cognitive behavior therapy for depression. Clinical Psychology, 1, Jones, R., Peveler, R. C., Hope, R. A. & Fairburn, C. G. (1993). Changes during treatment for bulimia nervosa: A comparison of three psychological treatments. Behaviour Research and Therapy, 31, Krupnick, J. L., Sotsky, S. M., Simmens, S., Moyer, J., Elkin, I., Watkins, J. & Pilkonis, P. A. (1996). The role of the therapeutic alliance in psychotherapy and pharmacotherapy outcome: Findings in the National Institute of Mental Health Treatment of Depression Collaborative Research Program. Journal ofconsulting and Clinical Psychology, 64, Laessle, R. G., Beumont, P. J. V., Butow, P., Lennerts, W., O'Connor, M., Pirke, K. M., Touyz, S. W. & Waadi, S. (1991). A comparison of nutritional management with stress management in the treatment of bulimia nervosa. British Journalof Psychiatry, 159, Leitenberg, H., Rosen, J. C., Wolf, J., Vara, L. S., Detzer, M. J. & Srebnik, D. (1994). Comparison of

14 Page 14 of 16 cognitive behavior therapy and desipramine in the treatment of bulimia nervosa. Behaviour Research and Therapy, 32, Luborsky, L. (1984). Principles of psychoanalytic psychotherapy (. New York: Basic Books) Luborsky, L. A., McLellen, A. T., Diguer, L., Woody, G. & Seligman, D. A. (1997). The psychotherapist matters: Comparison of outcomes across twenty-two therapists and seven patient samples. Clinical Psychology: Science and Practice, 4, Mathews, A. M., Johnston, D. W., Lancashire, M., Munby, M., Shaw, P. M. & Gelder, M. G. (1976). Imaginal flooding and exposure to real phobic situations: Treatment outcome with agoraphobic patients. British Journal of Psychiatry, 129, Mitchell, J. E., Pyle, R. L., Eckert, E. D., Hatsukami, D., Pomeroy, C. & Zimmerman, R. (1989). Response to alternative antidepressants in imipramine nonresponders with bulimia nervosa. Journal of Clinical Psychopharmacology, 9, Mitchell, J. E., Pyle, R. L., Eckert, E. D., Hatsukami, D., Pomeroy, C. & Zimmerman, R. (1990). A comparison study of antidepressants and structured intensive group psychotherapy in the treatment of bulimia nervosa. Archives of GeneralPsychiatry, 47, Mitchell, J. E., Pyle, R., Eckert, E. D., Hatsukami, D. & Soll, E. (1990). The influence of prior alcohol and drug abuse problems on bulimia nervosa treatment outcome. Addictive Behaviors, 15, Quitkin, F. M., McGrath, P., Stewart, J. W., Ocepek-Welikson, K. O., Taylor, B. P., Nunes, E., Deliyannides, D., Agosti, V., Donovan, S. J., Petkova, E. & Klein, D. F. (1996). Chronological milestones to guide drug change. Archives of General Psychiatry, 53, Rossiter, E. M., Agras, W. S., Telch, C. F. & Schneider, J. A. (1993). Cluster B personality disorder characteristics predict outcome in the treatment of bulimia nervosa. International Journal of Eating Disorders, 13, Spitzer, R. L., Williams, J. B. & Gibbon, M. (1987). Structured Clinical Interview for the DSM III R (SCID). (New York: New York State Psychiatric Institute, BiometricsResearch.) Strasser, T. J., Pike, K. M. & Walsh, B. T. (1992). The impact of prior substance abuse on treatment outcome for bulimia nervosa. Addictive Behaviors, 17, Walsh, B. T., Hadigan, C. M., Devlin, M. J., Gladis, M. & Roose, S. P. (1991). Long-term outcome of antidepressant treatment for bulimia nervosa. American Journal ofpsychiatry, 148, Walsh, B. T., Wilson, G. T., Loeb, K. L., Devlin, M. J., Pike, K. M., Roose, S. P., Fleiss, J. & Waternaux, C. (1997). Medication and psychotherapy in the treatment of bulimia nervosa. American Journal of Psychiatry, 154, Wilson, G. T. (1989). Cognitive behavioral treatment for bulimia nervosa. (Unpublished manuscript, Rutgers,The State University of New Jersey.) Wilson, G. T. (1998). Manual-based treatment and clinical practice. Clinical Psychology: Science andpractice, 5, Wilson, G. T. & Fairburn, C. G. (1998). Treatment of eating disorders.(in P. E. Nathan & J. M. Gorman (Eds.), Treatments that work (pp ). New York: Oxford University Press.) Wilson, G. T., Rossiter, E., Kleifield, E. & Lindholm, L. (l986). Cognitive behavioral treatment of bulimia nervosa: A controlled evaluation. Behaviour Research and Therapy, 24, Table 1. Design of Study of Medication and Psychological Treatment in the Treatment of Bulimia Nervosa: The Five Treatment Conditions

15 Page 15 of 16 Table 2. Mean Helping Relationship Questionnaire (HRQ) Scores by Treatment Condition Figure 1. Kaplan-Meier survival curve: Time to 75% persistent reduction of weekly baseline vomiting frequency (log-rank test = 26.4 on 3 df s, p =.0001). CBT = cognitive behavioral therapy; active = active medication; SPT = supportive psychotherapy. Figure 2. Kaplan-Meier survival curves: Time to 75% persistent reduction of weekly baseline vomiting frequency (for BDI < 20, log-rank test = 7.4 on 3 df s, p =.0609; for BDI > 20, log-rank test = 32.7 on 3 df s, p =.0001). BDI = Beck Depression Inventory; CBT = cognitive behavioral therapy; active = active medication; SPT = supportive psychotherapy. Figure 3. Weekly vomiting frequency for Weeks 4 16 (Sessions 7 20) by psychological treatment (CBT or SPT) and response status (rapid or slow). CBT = cognitive behavioral therapy; SPT = supportive psychotherapy.