Initial Severity and Differential Treatment Outcome in the National ...

Copyright 1995 by the American Psychological Association, Inc. 0022-006X/95/J3.00

Journal of Consulting and Clinical Psychology 1995, Vol.63, No.5,841-847

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This document is copyrighted by the American Psychological Association or one of its allied publishers. This article is intended solely for the personal use of the individual user and is not to be disseminated broadly.

Initial Severity and Differential Treatment Outcome in the National Institute of Mental Health Treatment of Depression Collaborative Research Program Robert D. Gibbons

Irene Elkin University of Chicago

University of Illinois at Chicago

Brown University and Veterans Affairs Medical Center

M. Trade Shea

Stuart M. Sotsky George Washington University Medical Center

John T. Watkins Center for Cognitive Therapy

University of Pittsburgh

Paul A. Pilkonis

Donald Hedeker University of Illinois at Chicago Random regression models (RRMs) were used to investigate the role of initial severity in the outcome of 4 treatments (cognitive-behavior therapy [CBT], interpersonal psychotherapy [IPT], imipramine plus clinical management [IMI-CM], and placebo plus clinical management [PLA-CM]) for outpatients with major depressive disorder seen in the National Institute of Mental Health Treatment of Depression Collaborative Research Program. Initial severity of depression and impairment of functioning significantly predicted differential treatment effects. A larger number of differences than previously reported were found among the active treatments for the more severely ill patients; this was due, in large part, to the greater power of the present statistical analyses.

Both the psychotherapy and the psychopharmacology literatures suggest that the initial level of symptoms and functioning, or severity of illness, can affect treatment outcome for various disorders (Garfield, 1994; Joyce & Paykel, 1989). Despite some ambiguity in the literature, the general direction of findings might lead one to expect somewhat better outcome for more severely depressed (nonpsychotic) outpatients in pharmaco-

Irene Elkin, School of Social Service Administration, University of Chicago; Robert D. Gibbons, Department of Psychiatry and Department of Biometry, School of Public Health, University of Illinois at Chicago; M. Tracie Shea, Department of Psychiatry and Human Behavior, Brown University, and Veterans Affairs Medical Center; Stuart M. Sotsky, George Washington University Medical Center; John T. Watkins, Center for Cognitive Therapy, Atlanta, Georgia; Paul A. Pilkonis, School of Medicine, University of Pittsburgh; Donald Hedeker, Department of Biometry, School of Public Health, University of Illinois at Chicago. The National Institute of Mental Health (NIMH) Treatment of Depression Collaborative Research Program is a multisite program initiated and sponsored by the Psychosocial Treatments Research Branch, Division of Extramural Research Programs (and later by the Mood, Anxiety, and Personality Disorders Research Branch, Division of Clinical Research), NIMH, Rockville, Maryland.

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therapy and for less severely depressed in psychotherapy. In the National Institute of Mental Health (NIMH) Treatment of Depression Collaborative Research Program (TDCRP), the possible differential role of severity in the different treatment conditions studied (cognitive-behavior therapy [CBT], interpersonal psychotherapy [IPT], imipramine plus clinical management [IMI-CM], and placebo plus clinical management [PLA-CM]) was considered of such importance that secondary analyses investigating the role of this variable were included in the first report of outcome findings (Elkin et al., 1989).' These preliminary results suggested that initial severity may play an important role in differential treatment effects. The purpose of the present article is to present further analyses of the relationship between initial severity of illness and outcome at termination of treatment, with recently developed, more powerful statististical procedures. Random regression models (RRMs) have already been applied to data for the total sample in the TDCRP, undifferentiated in terms of initial se1

The term cognitive behavior therapy is used throughout this article, as it has been in all previous reports of the TDCRP, although it should be clear that the therapy was conducted as described by A. T. Beck in the book Cognitive Therapy of Depression (Beck, Rush, Shaw, & Emery, 1979).

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verity of illness (Gibbons et al, 1993). We used the same statistical approach in the analyses reported here, taking initial severity into account. Method


Design The design and procedures of the TDCRP have already been described in some detail (Elkin et al., 1989). We, therefore, present only a brief overview here. The TDCRP was a collaborative clinical trial in which an identical research protocol was conducted at three research sites (George Washington University, the University of Pittsburgh, and the University of Oklahoma). The design of the TDCRP was thus a 3 (Research Sites) X 4 (Treatment Conditions) factorial design, with 250 patients randomly assigned to the four treatment conditions: CBT, IPT, IMI-CM, and PLA-CM.2 IMI-CM served as a standard reference treatment; PLA-CM, which was introduced into the study largely as a control for IMI-CM, also served as a stringent control condition for the two psychotherapies. To be included in the study, patients had to meet Research Diagnostic Criteria (Spitzer, Endicott, & Robins, 1978) for a current episode of major depressive disorder and have a score of 14 or greater on an amended version of the 17-item Hamilton Rating Scale for Depression (HRSD; Hamilton, 1967). Treatments were conducted in accord with manuals prepared by the developers of each of the psychotherapies (Klerman, Weissman, Rounsaville, & Chevron, 1984, for IPT; Beck, Rush, Shaw, & Emery, 1979, for CBT) and by the trainer for the pharmacotherapy conditions (Faw-

The principal NIMH collaborators were Irene Elkin, Coordinator (now at the University of Chicago); M. Tracie Shea, Associate Coordinator (now at Brown University); John P. Docherty (now at Nashua Brookside Hospital); and Morris B. Parloff(now at Georgetown University). The principal investigators and project coordinators at the three participating research sites were as follows: Stuart M. Sotsky and David Glass, George Washington University; Stanley D. Imber and Paul A. Pilkonis, University of Pittsburgh; and John T. Watkins (now at the Center for Cognitive Therapy, Atlanta, Georgia) and William Leber, the University of Oklahoma. The principal investigators and project coordinators at the three sites responsible for training therapists were as follows: Myrna Weissman, Eve Chevron, and Bruce J. Rounsaville, Yale University (Myrna Weissman is now at Columbia University); Brian F. Shaw and T. Michael Vallis, Clarke Institute of Psychiatry; and Jan A. Fawcett and Phillip Epstein, Rush Presbyterian—St. Luke's Medical Center. Collaborators in the data management and data analysis aspects of the program were C. James Klett, Joseph F. Collins, and Roderic Gillis of the Veterans Affairs Cooperative Studies Program, Perry Point, Maryland. The program was funded by Cooperative Agreements to six participating sites; MH 33762 to George Washington University; MH 33753 to the University of Pittsburgh; MH 33760 to the University of Oklahoma, Oklahoma City; MH 33827 to Yale University; MH 38231 to the Clarke Institute of Psychiatry, Toronto, Ontario, Canada; and MH 35017 to Rush Presbyterian—St Luke's Medical Center. The analyses for this article were funded in part by a grant from the John D. and Catherine T. MacArthur Foundation and by Grant RO1 MH 4426-01 from the Services Research Branch of NIMH. We thank David Kupfer for his support and Joseph Collins and Jane Yamaguchi for their assistance in the data analysis and preparation of this article. Correspondence concerning this article should be addressed to Irene Elkin, School of Social Service Administration, University of Chicago, 969 East 60th Street, Chicago, Illinois 60637.

cett, Epstein, Fiester, Elkin, & Autry, 1987). A different group of therapists conducted treatment in each of the conditions, with the exception of the two pharmacotherapy conditions, which were carried out in a double-blind manner by the same therapists. The 28 therapists who took part in the study were carefully selected, received further training in their respective treatment approaches, and had to meet criteria for conducting the treatment in a competent fashion. All treatments were planned to be 16 weeks long, with a range of 16 to 20 sessions. There were no statistically significant differences in attrition (which ranged from 23% to 40%) among the four treatment conditions. Patients were assessed before treatment, at several points during treatment (4, 8, and 12 weeks), at termination, and at 6-, 12-, and 18month follow-up. The present analyses are based on data derived from three of the major measures of depressive symptomatology and impairment of functioning: the (unamended) 17-item HRSD (Hamilton, 1967), the Global Assessment Scale (GAS; Endicott, Spitzer, Fleiss, & Cohen, 1976), and the Beck Depression Inventory (BDI; Beck et al., 1979).3 Intraclass correlations for ratings by independent clinical evaluators across sites ranged from .93 to .96 for the HRSD and from .83 to .88 for the GAS.

Statistical A nalysis The major question to be addressed in the present analyses is the following: Is there a difference in the effectiveness of the treatments in the TDCRP that is conditional on the initial severity of the patient's illness? Separate random regression analyses were conducted using the full range of scores on the HRSD or the GAS to assess initial severity. Because of the somewhat different results found in the original analyses when using HRSD or GAS severity criteria, a third analysis combined these two measures in a single model. Finally, an additional analysis was conducted using a self-report measure, the BDI, to assess severity. The dependent variables in these analyses are scores on the 17-item HRSD and the BDI. The RRMs used in these analyses make use of all available data for all patients for a particular dependent variable. (These data include those obtained at all regularly scheduled evaluations: baseline, 4 weeks, 8 weeks, 12 weeks, and termination; they do not include unscheduled evaluations or early termination evaluations.) The general model posits that the individual response of each participant can be described by a line with intercept (baseline response) and slope (improvement rate) that is specific to the individual. Conceptual details of the model and relevant statistical references are presented in Gibbons et al. (1993). All analyses were performed using the computer program MIXREG (Hedeker, 1993). Previous analyses of these data (Gibbons et al., 1993) revealed that person-specific deviations in severity at baseline did not represent a significant component of variance, but variation in trend was significant; thus, a single random effect (i.e., random trend model) was used. In this case, it was found that approximate linearity could be achieved by using a logarithmic transformation on time (loge [weeks + 1 ]). Thus all figures depict predicted mean responses at each time point, graphed with time on a logarithmic scale. The previous RRM analyses found no evidence of Treatment X Site interactions, although main effects of site were included in the models.4 2

Of the 250 patients assigned, 239 actually began treatment. The traditional 17-item HRSD score was used here to yield findings comparable with those of most studies in the depression literature. 4 Exploratory analyses of outcome data for the more severely depressed and functionally impaired patients did suggest the presence of a Treatment X Site interaction within this subgroup (Elkin et al., 1989). This will be explored further in future analyses. 3

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Table 1 Effect of Initial Severity as Measured by the Hamilton Rating Scalefor Depression (HRSD) on the HRSD Time Trend


Baseline HRSD score