Cognitive Behavioral Analysis System of Psychotherapy as a Maintenance Treatment for Chronic Depression

Transcription

1 Journal of Consulting and Clinical Psychology Copyright 2004 by the American Psychological Association 2004, Vol. 72, No. 4, X/04/$12.00 DOI: / X Cognitive Behavioral Analysis System of Psychotherapy as a Maintenance Treatment for Chronic Depression Daniel N. Klein, Neil J. Santiago, and Dina Vivian State University of New York at Stony Brook Janice A. Blalock University of Texas Medical Branch at Galveston Bruce A. Arnow Stanford University School of Medicine David L. Dunner University of Washington School of Medicine James H. Kocsis and John C. Markowitz Cornell University Medical College James P. McCullough Jr. Virginia Commonwealth University A. John Rush and Madhukar H. Trivedi University of Texas Southwestern Medical Center at Dallas Frances E. Borian Bristol-Myers Squibb Rachel Manber University of Arizona School of Medicine Barbara Rothbaum Emory University School of Medicine Michael E. Thase University of Pittsburgh Medical Center Gabor I. Keitner, Ivan W. Miller, and Martin B. Keller Brown University School of Medicine Although the efficacy of maintenance pharmacotherapy for the prevention of recurrence in major depressive disorder (MDD) is well documented, few studies have tested the efficacy of psychotherapy as a maintenance treatment. The authors examined the efficacy of the cognitive behavioral analysis system of psychotherapy (CBASP) as a maintenance treatment for chronic forms of MDD. Eighty-two patients who had responded to acute and continuation phase CBASP were randomized to monthly CBASP or assessment only for 1 year. Significantly fewer patients in the CBASP than assessment only condition experienced a recurrence. The 2 conditions also differed significantly on change in depressive symptoms over time. These findings support the use of CBASP as a maintenance treatment for chronic forms of MDD. In recent years there has been growing recognition that depression is often a recurrent or chronic disorder and that it is insufficient to simply treat depressed patients until their symptoms have remitted (Kupfer, 1991). Current guidelines recommend 4 9 months of continuation treatment after the patient has responded to acute phase treatment to minimize the risk of relapse. For patients with a history of recurrent or chronic depression, at least 1 2 years of maintenance treatment is recommended to reduce the risk of recurrence (American Psychiatric Association, 2000; Depression Guideline Panel, 1993). A number of studies have documented the efficacy of continuation and maintenance pharmacotherapy for recurrent and chronic Daniel N. Klein, Neil J. Santiago, and Dina Vivian, Department of Psychology, State University of New York at Stony Brook; Bruce A. Arnow, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine; Janice A. Blalock, Department of Psychiatry, University of Texas Medical Branch at Galveston; David L. Dunner, Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine; James H. Kocsis and John C. Markowitz, Department of Psychiatry, Cornell University Medical College; Rachel Manber, Department of Psychiatry, University of Arizona School of Medicine; James P. McCullough Jr., Department of Psychology, Virginia Commonwealth University; Barbara Rothbaum, Department of Psychiatry, Emory University School of Medicine; A. John Rush and Madhukar H. Trivedi, Department of Psychiatry, University of Texas Southwestern Medical Center at Dallas; Michael E. Thase, Department of Psychiatry, University of Pittsburgh Medical Center; Frances E. Borian, Bristol-Myers Squibb, New York; Gabor I. Keitner, Ivan W. Miller, and Martin B. Keller, Department of Psychiatry and Human Behavior, Brown University School of Medicine. Janice A. Blalock is now at the Department of Behavioral Science, University of Texas M. D. Anderson Cancer Center; Rachel Manber is now at the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine. This research was supported by Bristol-Myers Squibb. Correspondence concerning this article should be addressed to Daniel N. Klein, Department of Psychology, State University of New York at Stony Brook, Stony Brook, NY dklein@notes.cc.sunysb.edu 681

2 682 KLEIN ET AL. forms of major depressive disorders (MDDs; Greden, 2001; Keller et al., 1998; Kocsis et al., 1996; Kupfer et al., 1992). In contrast, few studies have examined the efficacy of continuation and maintenance psychotherapy for depression (Rush & Thase, 1998). We are aware of only six controlled studies of continuation and/or maintenance phase psychotherapy for MDD (Blackburn, Eunson, & Bishop, 1986; Blackburn & Moore, 1997; Frank et al., 1990; Jarrett et al., 2001; Klerman, DiMascio, Weissman, Prusoff, & Paykel, 1974; Reynolds et al., 1999). Of the three continuation studies, two used cognitive therapy (CT) and found that CT was as effective as pharmacotherapy (Blackburn et al., 1986) or more effective than assessment only (Jarrett et al., 2001) in preventing relapse. The third continuation study found that interpersonal psychotherapy (IPT) did not have a significant effect on relapse but was associated with better social adjustment (Klerman et al., 1974; Weissman, Klerman, Paykel, Prusoff, & Hanson, 1974). One study combining the continuation and maintenance phases found that CT was as effective as pharmacotherapy in preventing recurrence (Blackburn & Moore, 1997). Finally, the only two maintenance studies both found that IPT was more effective than placebo in preventing recurrence (Frank et al., 1990; Reynolds et al., 1999). In addition, four studies have examined the efficacy of brief psychotherapy following acute phase pharmacotherapy in patients who have recovered or partially recovered from MDD in the prevention of relapse or recurrence (Fava, Grandi, Zielezny, Rafanelli, & Canestrari, 1996; Fava, Rafanelli, Grandi, Conti, & Belluardo, 1998; Paykel et al., 1999; Teasdale et al., 2000). All of these studies found that variants of CT reduced the risk of relapse compared with clinical management with or without continued pharmacotherapy or treatment as usual. The present article reports the results of the psychotherapy arm of the maintenance phase of a multisite study of the acute and long-term treatment of chronic forms of MDD (Keller et al., 2000). The study included four phases. First, in the acute phase, patients were randomized to 12 weeks of treatment with the cognitive behavioral analysis system of psychotherapy (CBASP; McCullough, 2000), nefazodone, which is an atypical antidepressant, or the combination of CBASP and nefazodone. As reported elsewhere (Keller et al., 2000), the response rate was significantly higher in the combination condition (73%) than in each of the two monotherapy conditions (both 48%). Second, nonresponders to each of the monotherapy conditions were crossed over for a 12-week trial of the other monotherapy. Third, responders in each of the three acute treatment conditions and responders in the two crossover conditions received 16 weeks of continuation phase treatment with the same intervention that they had responded to. Finally, patients who maintained their response through the continuation phase entered one of two arms of a 52-week maintenance study. Patients who completed continuation treatment with nefazodone monotherapy or combined treatment entered the pharmacotherapy arm of the maintenance phase and were randomized to nefazodone alone or placebo alone. As reported elsewhere (Gelenberg et al., 2003), patients receiving nefazodone were significantly less likely to experience a recurrence than were patients receiving placebo. Patients who completed the continuation phase on CBASP monotherapy entered the psychotherapy arm of the maintenance phase and were randomized to CBASP or assessment only. We present the results of this latter comparison here. To our knowledge, this is only the third maintenance study of the psychotherapy of depression to date and the first using an approach other than IPT. In addition, as all previous continuation and maintenance psychotherapy studies have focused on MDD in general (Blackburn et al., 1986; Klerman et al., 1974) or recurrent MDD (usually with full recovery between episodes; Blackburn & Moore, 1997; Frank et al., 1990; Jarrett et al., 2001; Reynolds et al., 1999), this is the first study to examine the efficacy of maintenance psychotherapy for chronic forms of MDD. Participants Method This report is based on 82 patients who (a) responded to CBASP alone in the acute phase (n 60) or failed to respond to nefazodone alone but subsequently responded to CBASP alone in the crossover phase (n 22), (b) maintained their response to CBASP alone during the continuation phase, and (c) entered the maintenance phase, in which they were randomized to continue CBASP (n 42) or receive assessments only (n 40). All patients provided informed consent. In the acute phase, 681 outpatients at 12 academic centers were randomized to 12 weeks of treatment with CBASP alone, nefazodone alone, or the combination. Patients met Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM IV; American Psychiatric Association, 1994) criteria for a current episode of chronic MDD, MDD superimposed on preexisting dysthymic disorder, or recurrent MDD with incomplete remission and a total duration of continuous illness of at least 2 years. Patients were between the ages of 18 and 75 years and had a score of at least 20 on the 24-item Hamilton Rating Scale for Depression (HRSD-24; Hamilton, 1967) at screening and, after a 2-week drug-free period, at baseline. Exclusion criteria included the following: (a) a history of psychotic, bipolar, or obsessive-compulsive disorder; (b) eating disorders within the past year; (c) substance abuse or dependence in the past 6 months; (d) a high risk for suicide; (e) antisocial, schizotypal, or severe borderline (i.e., high risk for hospitalization) personality disorder; (f) poorly controlled or serious medical disorders; and (g) a history of failing three adequate trials of antidepressant medications from at least two different classes, two different courses of empirically supported psychotherapy for depression, or a trial of electroconvulsive therapy, in the past 3 years. In the acute, crossover, and continuation phases, response was defined as a reduction from the acute phase baseline of at least 50% and a total score of 15 or less on the HRSD-24. Of the 228 patients initially assigned to acute phase treatment with CBASP alone, 89 completed the acute phase, responded, and entered the continuation phase. Of these 89 patients, 60 maintained their response during the continuation phase and were randomized to maintenance CBASP or assessment only. Of the 226 patients initially assigned to acute phase treatment with nefazodone alone, 73 completed the acute phase but failed to respond. Of these 73 patients, 34 completed the 12-week crossover phase, responded to CBASP alone, and entered the continuation phase. Of these 34 patients, 22 maintained their response during the continuation phase and were randomized to maintenance CBASP or assessment only. Treatment Conditions CBASP is an integrative, manualized, time-limited psychotherapy developed to treat chronic depression (McCullough, 2000). It combines elements of behavioral, cognitive, interpersonal, and psychodynamic psychotherapy. The major goals of CBASP include helping patients change their patterns of coping, improve their interpersonal skills, understand the consequences of their behavior, and interact more effectively with others.

3 MAINTENANCE PSYCHOTHERAPY FOR CHRONIC DEPRESSION 683 CBASP is similar to cognitive and behavioral approaches in that it is highly structured, focuses on teaching social problem solving skills, and makes use of regular homework assignments; it is similar to IPT in its focus on interpersonal problems, and it borrows from psychodynamic psychotherapy in that the relationship with the therapist can be used as a tool to help patients become more aware of their impact on others and distinguish between adaptive and maladaptive relationships (McCullough, 2000). The major technique used in CBASP is situational analysis (SA). In SA, patients identify a recent, distressing, interpersonal situation and examine it with the therapist. The process consists of three phases: elicitation, remediation, and generalization. In the elicitation phase, patients describe: (a) the interpersonal event, (b) their interpretation of what occurred, (c) their behavior, (d) the outcome of the event (actual outcome), (e) what they would have liked the outcome to be (desired outcome), and (f) whether the desired outcome was achieved. In the remediation phase, patients work with the therapist to revise their interpretations, behaviors, and/or desired outcome during the situation to increase the probability of achieving the desired outcome. In the generalization phase, patient and therapist review what has been learned and explore how the patient s new understanding and skills could be applied to similar situations in the past and future. Patients received sessions of CBASP during the 12-week acute phase (2 sessions per week during Weeks 1 4, 1 2 sessions per week during Weeks 5 8, and 1 session per week during Weeks 9 12) and 6 sessions of CBASP during the 16-week continuation phase (one session every 2 weeks during Weeks 1 8 and 1 session every 4 weeks during Weeks 9 16). Patients who were randomized to continue CBASP in the 52-week maintenance phase received 1 session every 4 weeks for a total of up to 13 sessions. Maintenance CBASP is similar in format and procedures to acute and continuation phase CBASP. Its goals include reviewing, reinforcing, and consolidating the skills that patients acquire in the earlier phases of treatment. In each session, patients complete an SA about a recent problematic interpersonal situation and review it with the therapist, going through the elicitation, remediation, and generalization phases described above. All therapists (N 52) had at least 2 years of clinical experience after earning a doctoral or master s degree, or at least 5 years of experience after earning a master of social work degree. They attended an intensive 2-day workshop conducted by James P. McCullough and met criteria for mastery of CBASP procedures based on a 12-week course of acute phase treatment with two pilot cases. Therapists were supervised by the designated supervisor at each site, who in turn was directly supervised by James P. McCullough. Supervision was conducted weekly during the acute phase and biweekly during the maintenance phase. Sessions were videotaped and reviewed weekly biweekly by the site supervisor or James P. McCullough to assess adherence to the treatment procedures. Adherence was assessed using a rating scale described in McCullough (2000). When nonadherence was identified, it was immediately discussed with the therapist and efforts at remediation were provided. In the assessment only condition, patients saw the project coordinator and an independent evaluator every 4 weeks (see below), which provided them with some attention and continued connection to the project but no active treatment. In addition, they received a small honorarium to compensate for time and travel expenses and to provide an incentive for continued participation in the study despite receiving no treatment. Patients in the CBASP condition were also seen by the independent evaluator every 4 weeks but did not receive an honorarium. All patients were reminded at each visit not to mention anything that might reveal their treatment condition to the independent evaluator. If patients had questions or concerns about the study, they were instructed to raise them with the project coordinator rather than the independent evaluator. In the rare instances that the blind was broken, the patient was seen by a different independent evaluator at subsequent visits. In both conditions, all psychotropic medication and nonprotocol psychotherapy were prohibited. Measures Diagnoses were derived using a modified version of the Structured Clinical Interview for DSM IV (SCID; First, Spitzer, Gibbon, & Williams, 1995) during the screening evaluation prior to entry into the acute phase. The primary outcome measure throughout all phases of the study was the HRSD-24, which was administered by certified raters who were unaware of patients treatment conditions (Keller et al., 2000). The HRSD-24 was supplemented by a self-rated measure, the 30-item Inventory of Depressive Symptoms, Self-Report version (IDS-SR-30; Rush, Guillion, Basco, Jarrett, & Trivedi, 1996). Both measures were administered every 4 weeks during the maintenance phase. If depressive symptoms began to emerge, as evidenced by a HRSD-24 score of 16 or greater, another evaluation was scheduled within 2 weeks. Evaluations continued every 2 weeks until either the symptoms subsided or protocol recurrence criteria were met. Recurrence was defined in the protocol as a HRSD-24 score of 16 or greater on two consecutive visits and a diagnosis of MDD as determined from a DSM IV MDD checklist administered by the independent evaluator. At the second of these visits, the recurrence also needed confirmation by the site s senior investigator on the basis of a clinical interview (Gelenberg et al., 2003). Because some patients had elevated HRSD-24 scores but did not meet MDD criteria, or they discontinued before the confirmatory visit, a committee of senior investigators conducted a masked review of all patient data at the end of the study (Gelenberg et al., 2003). Recurrence was declared if there was consensus among the committee that an episode of MDD had occurred. The committee also indicated the date of the onset of the recurrence. The data were analyzed by use of both the protocol and the consensus definitions of recurrence. Results Descriptive Characteristics of the Sample We conducted two sets of preliminary analyses. First, we compared the 82 patients in the psychotherapy arm of the maintenance study to the remaining 599 patients who entered the study on baseline demographic and clinical characteristics (see Table 1) using chi-square tests for categorical variables and t tests for continuous variables. Yates s correction for continuity was used for chi-square tests on 2 2 tables. None of these comparisons were statistically significant. Second, we compared the 42 patients who were randomized to continue CBASP in the maintenance phase to the 40 patients who were randomized to the assessment only condition on demographic and clinical features. At entry into the acute phase of the study, patients ultimately assigned to the CBASP and assessment only conditions did not differ on age, race, marital status, type of chronic depression diagnosis, HRSD-24 score, age of onset of MDD, duration of index MDD episode, lifetime number of episodes of MDD, history of anxiety disorder, and history of substance use disorder (see Table 2). In addition, the two groups did not differ on HRSD-24 and IDS-SR-30 scores at maintenance phase baseline. Despite randomization, the two groups differed on gender, with a significantly greater proportion of women receiving CBASP, 2 (1, N 82) 6.28, p.01. Patients in the CBASP condition received a mean 11.1 (SD 3.8) psychotherapy sessions during the maintenance phase. Ten patients (23.8%) in the CBASP condition and 11 patients (27.5%) in the assessment only condition dropped out prior to the end of the maintenance phase for reasons other than recurrence, 2 (1, N 82) 0.17, p.90. Correlations between patients HRSD-24

4 684 KLEIN ET AL. Table 1 Comparison of Descriptive Characteristics Between Patients Who Did and Did Not Participate in the Psychotherapy Arm of the Maintenance Study Participated in psychotherapy arm of maintenance study Variable No (N 599) Yes (N 82) scores at entry into the maintenance phase and their final visit, and between their IDS-SR-30 scores at entry and final visit, were.45 ( p.001) and.57 ( p.001), respectively. Recurrence Age, M (SD) 43.0 (10.6) 45.1 (11.4) Gender, n (%) Female 390 (65.1) 55 (67.1) Male 209 (34.9) 27 (32.9) Race, n (%) White 541 (90.3) 75 (91.5) Marital status, n (%) Single 164 (27.4) 21 (25.6) Married cohabiting 251 (41.9) 40 (48.8) Divorced separated 171 (28.5) 20 (24.4) Widowed 13 (2.2) 1 (1.2) Chronic depression diagnosis, n (%) Chronic MDD 207 (34.6) 32 (39.0) Recurrent MDD with incomplete remission between episodes 136 (22.7) 18 (22.0) MDD with dysthymic disorder 124 (20.7) 19 (23.2) Chronic MDD with dysthymic disorder 132 (22.0) 13 (15.9) Acute phase baseline HRSD-24 M (SD) 27.0 (5.1) 26.0 (4.1) Age of onset of MDD in years, M (SD) 26.6 (13.2) 28.2 (12.9) Duration of index MDD episode in years, M (SD) 7.9 (9.5) 7.4 (9.8) Lifetime number of MDD episodes, M (SD) 2.6 (3.7) 2.4 (1.6) History of anxiety disorder, n (%) 200 (33.4) 23 (28.0) History of substance use disorder, n (%) 205 (34.2) 21 (25.6) Note. MDD major depressive disorder; HRSD item Hamilton Rating Scale for Depression. We compared time to recurrence between the CBASP and assessment only groups using survival analysis. Patients who failed to complete the maintenance phase were included in these analyses using all available data up to the time of exiting the study. Using the protocol definition, Kaplan Meier product-limit estimates of the rates of recurrence were 2.6% in the CBASP condition compared with 20.9% in the assessment only condition, log rank test(1) 4.76, p.03 (see Figure 1). Using the consensus definition, we found that the estimated recurrence rates were 10.7% and 32.0% in the CBASP and assessment only conditions, respectively, log rank test(1) 3.99, p.05 (see Figure 2). In both analyses the protective effects of CBASP appeared to emerge after 5 6 months of maintenance treatment. There were two different routes of entry into the maintenance phase: (a) acute to continuation to maintenance and (b) acute to crossover to continuation to maintenance. The number of patients participating in the crossover phase did not differ between the two treatment conditions (see Table 2). In addition, the recurrence rates for patients who participated in the crossover phase and those who responded to CBASP as an initial treatment did not differ, protocol definition, log rank test(1) 0.39, p.53; consensus definition, log rank test(1) 0.19, p.66. Nonetheless, we conducted an additional set of analyses stratifying on the basis of crossover participation. Pooled over the two strata, the two treatment conditions differed significantly on time to recurrence according to both the protocol definition, log rank test(1) 4.23, p.04, and the consensus definition, log rank test(1) 3.77, p.05. Finally, although the two treatment conditions differed on gender distribution, gender did not predict recurrence using the protocol definition, log rank test(1) 2.35, p.13, or consensus definition, log rank test(1) 0.91, p.34. Nonetheless, we conducted a final set of analyses stratifying on gender. Pooled over the two strata, the differences between treatment conditions on recurrence rates were reduced to trend levels of statistical significance, log rank test(1) 2.93, p.09, and log rank test(1) 3.17, p.08, for the protocol and consensus definitions, respectively. Depressive Symptoms We also compared the two treatment conditions on change in interview- and self-rated depressive symptoms over time using mixed effects linear growth curve models, with time in weeks as the within-subjects (or Level 1) variable, and treatment condition, crossover participation, and gender as the between-subjects (or Level 2) variables (Raudenbush & Bryk, 2001). HRSD-24 and IDS-SR-30 scores were square-root transformed to reduce skew. Level 2 variables were centered at their grand mean. The intercept, which was centered at entry into the maintenance phase, and slope were treated as random effects. Treatment condition, crossover participation, and gender were treated as fixed effects. Robust standard errors were used. All variables were entered simultaneously so that any effect of treatment condition on the slope of depressive symptoms was over and above the effects of crossover

5 MAINTENANCE PSYCHOTHERAPY FOR CHRONIC DEPRESSION 685 Table 2 Descriptive Characteristics of the Sample Variable CBASP (N 42) Assessment only (N 40) Age, M (SD) 44.2 (11.7) 46.0 (11.1) Sex, n (%) Female 34 (81.0) 21 (52.5)* Male 8 (19.0) 19 (47.5) Race, n (%) White 38 (90.5) 37 (92.5) Marital status, n (%) Single 14 (33.3) 7 (17.5) Married cohabiting 19 (45.2) 21 (52.5) Divorced separated 9 (21.4) 11 (27.5) Widowed 0 (0.0) 1 (2.5) Chronic depression diagnosis, n (%) Chronic MDD 15 (35.7) 17 (42.5) Recurrent MDD with incomplete remission between episodes 10 (23.8) 8 (20.0) MDD with dysthymic disorder 11 (26.2) 8 (20.0) Chronic MDD with dysthymic disorder 6 (14.3) 7 (17.5) Acute phase baseline HRSD-24, M (SD) 26.1 (4.0) 26.0 (4.3) Age of onset of MDD in years, M (SD) 27.0 (12.4) 29.5 (13.5) Duration of index MDD episode in years, M (SD) 7.7 (9.6) 7.1 (10.2) Lifetime number of MDD episodes, M (SD) 2.5 (1.6) 2.4 (1.5) History of anxiety disorder, n (%) 12 (28.6) 10 (25.0) History of substance use disorder, n (%) 9 (21.4) 12 (30.0) Participation in crossover phase, n (%) 10 (23.8) 12 (30.0) Maintenance baseline HRSD-24, M (SD) 6.6 (3.8) 6.2 (4.4) End of maintenance HRSD-24, M (SD) 6.3 (5.6) 10.3 (8.2) Maintenance baseline IDS-SR-30, M (SD) 9.7 (6.8) 10.0 (6.5) End of maintenance IDS-SR-30, M (SD) 9.1 (7.7) 13.2 (8.5) Note. CBASP Cognitive behavioral analysis system of psychotherapy; MDD major depressive disorder; HRSD item Hamilton Rating Scale for Depression; IDS-SR item Inventory of Depressive Symptoms, Self-Report version. * p.01. participation and gender. Patients who failed to complete the maintenance phase were included in these analyses using all available data up to the time of exiting the study. Baseline and endpoint HRSD-24 and IDS-SR-30 scores are presented in Table 2, and estimated linear trends over time are presented in Figures 3 and 4. Nontransformed scores are presented to facilitate interpretation. In the model for the HRSD-24, there was a small negative correlation between the intercept and the slope (r.08). The effects of treatment condition, crossover participation, and gender on the intercept were nonsignificant. However, there was a significant linear effect of treatment condition on time, B.01035, SE.00312, t 3.31, df 78, p.001, which is analogous to a Treatment Time interaction in a repeated measures analysis of variance. The effects of crossover participation and gender on time were not significant (see Figure 3). In the model for the IDS-SR-30, a small negative correlation between the intercept and the slope (r.14) was again evident. The effects of treatment condition, crossover participation, and gender on the intercept were nonsignificant. The linear effect of treatment condition on time was statistically significant, B.01081, SE.00367, t 2.95, df 77, p.004. However, there were no significant effects of crossover participation and gender on time (see Figure 4). As can be seen in Figures 3 and 4, on both the HRSD-24 and IDS-SR-30, levels of depressive symptoms increased over time among patients in the assessment only condition but decreased over time in patients in the CBASP condition. Discussion The present study adds to the small but growing literature indicating the benefits of continuation and maintenance psychotherapy for recurrent and chronic forms of MDD. We randomized patients who had responded to an intensive 12-week acute phase course of CBASP and maintained their response through a 16- week continuation phase to 52 weeks of maintenance phase CBASP (with sessions conducted every 4 weeks) or assessment only. Patients in the maintenance CBASP condition had a 3 10 times lower rate of recurrence depending on the definition of recurrence used. The CBASP and assessment only conditions also differed significantly on the direction of change of depressive symptoms. Patients receiving assessment only experienced a small increase in symptoms over time, whereas patients receiving CBASP exhibited a small reduction in symptoms over time. The latter effect suggests that the benefits of maintenance CBASP may go beyond recurrence prevention and include continued (albeit slight) reduction of subthreshold symptoms. The results of this study are consistent with previous studies demonstrating that continuation CT is associated with a significantly lower probability of relapse (Jarrett et al., 2001) and maintenance IPT is associated with a significantly lower likelihood of recurrence (Frank et al., 1990; Reynolds et al., 1999) compared with placebo or assessment only in patients with recurrent MDD. The present study extends this literature by reporting a third

6 686 KLEIN ET AL. Figure 1. Kaplan Meier survival curves comparing cognitive behavioral analysis system of psychotherapy (CBASP) with assessment only using protocol definition of recurrence. Solid line indicates the CBASP condition; dashed line indicates the assessment only condition; cross-hatches indicate censored observations. The two curves differ significantly, log rank test 4.76, df 1, p.03. Figure 3. Mixed effects growth curve model comparing cognitive behavioral analysis system of psychotherapy (CBASP) with assessment only on estimated nontransformed 24-item Hamilton Rating Scale for Depression (HRSD-24) scores, with gender and participation in the crossover phase as covariates. Linear effect of treatment condition on time, t 3.31, df 78, p.001. maintenance study using a different approach to psychotherapy (CBASP) and focusing on patients with chronic forms of MDD. It is difficult to directly compare relapse and recurrence rates across studies because of differences in samples, study designs, durations and types of treatment, definitions of recurrence, and data analytic strategies. It is also hazardous to compare the recurrence rates in the psychotherapy and pharmacotherapy arms of the maintenance phase of the present study because patients who entered the maintenance phase from different acute and continuation phase treatments may represent somewhat different populations with differing risks for recurrence (a phenomenon referred to as a differential sieve by Hollon, Shelton, & Loosen, 1991). Nonetheless, it is of interest that the recurrence rate (consensus definition) in the placebo condition of the pharmacotherapy arm of the maintenance study (48%; Gelenberg et al., 2003) was higher than for the assessment only condition in the psychotherapy arm of the study (32%; see Results). It is tempting to speculate that acute Figure 2. Kaplan Meier survival curves comparing cognitive behavioral analysis system of psychotherapy (CBASP) with assessment only using consensus definition of recurrence. Solid line indicates the CBASP condition; dashed line indicates the assessment only condition; cross-hatches indicate censored observations. The two curves differ significantly, log rank test 3.99, df 1, p.05. Figure 4. Mixed effects growth curve model comparing cognitive behavioral analysis system of psychotherapy (CBASP) with assessment only on estimated nontransformed 30-item Inventory of Depressive Symptoms, Self-Report version (IDS-SR-30) scores, with gender and participation in the crossover phase as covariates. Linear effect of treatment condition on time, t 2.95, df 77, p.004.

7 MAINTENANCE PSYCHOTHERAPY FOR CHRONIC DEPRESSION 687 and continuation CBASP may have lowered the risk of recurrence in the assessment only condition during the maintenance phase. However, we reported elsewhere that there was no significant long-term advantage for acute and continuation phase combination (nefazodone plus CBASP) treatment compared with acute and continuation phase treatment with nefazodone alone during the maintenance phase (Gelenberg et al., 2003). Thus, the question of whether CBASP has long-term effects that persist after the termination of treatment remains open. Our study had a number of strengths, including a rigorously diagnosed sample, random assignment to treatment condition at the beginning of the maintenance phase, a no treatment control condition, independent evaluations by blinded raters, a wellspecified treatment approach, a large number of psychotherapists, and the use of both interview and self-report measures of depression. However, the study also had a number of limitations. First, the number of participants was modest, although the size of each of the groups was larger than the treatment groups in all of the previous psychotherapy continuation and maintenance studies other than that of Jarrett et al. (2001), whose Ns were very similar to ours. Second, because of the modest sample size and large number of sites in this multisite trial, we were unable to examine site effects. However, few Site Treatment interactions have been identified in the other phases of this study (Gelenberg et al., 2003; Keller et al., 2000). Third, despite randomizing patients to treatment condition at the beginning of the maintenance phase, the two treatment groups differed on gender. Although gender was not related to recurrence, stratifying on gender reduced the effects of treatment condition on time-to-recurrence to trend levels. However, the mixed effects growth curve models of depressive symptoms remained significant even after controlling for gender. Fourth, the comparison condition consisted of assessments without any formal treatment. Thus, it is unclear whether our findings are specific to CBASP, extend to other antidepressant treatments (psychosocial or pharmacological), or are due to greater contact time and attention. Studies using active and placebo comparison conditions are needed to address these questions. Fifth, we did not conduct a formal interrater reliability study of the SCID or HRSD-24 assessments. However, the independent evaluators completed an intensive training workshop on both instruments, and the evaluators were certified by an expert rater at another site on the basis of videotapes of a SCID and a HRSD-24 assessment that the rater conducted with a patient with chronic depression. Sixth, many patients failed to respond to acute or crossover phase CBASP, failed to maintain their response to continuation phase CBASP, or dropped out of the study prior to the maintenance phase. Specifically, only 82 of the 301 patients (27.2%) who were randomized to receive CBASP alone in the acute phase or were crossed over to CBASP after failing to respond to acute phase nefazodone alone were eligible for, and participated in, the maintenance study. Although the patients who participated in the CBASP arm of the maintenance study did not differ from the remaining patients in the original sample on any major demographic or clinical variable, it is important to bear in mind that our findings can be generalized only to the subgroup of patients with chronic forms of MDD with a sustained response to CBASP. Seventh, 21 of the 82 patients (25.6%) entering the maintenance phase dropped out of the study at some point before recurrence or completion. Although we used data analytic techniques that made use of all data up to the point of dropout, we cannot rule out the possibility that the findings were biased in unknown ways by these early exits. Finally, this was an efficacy study conducted in academic settings with a number of inclusion and exclusion criteria. Thus, it remains to be seen whether the results will generalize to the broader population of chronically depressed patients treated in community settings. Although the present findings are encouraging, further work is necessary to compare the efficacy and cost-effectiveness of different types of maintenance psychotherapies and to compare maintenance psychotherapy with maintenance pharmacotherapy and with the alternative strategy of initiating a brief course of psychotherapy after treating patients to full or partial remission with medication (Fava et al., 1996, 1998; Paykel et al., 1999; Teasdale et al., 2000). 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