PATIENTS AND METHODS
The recruitment and protocol were approved by the institutional review board. Patients (n>3500; recruited through media, announcements, and referrals) were triaged by telephone. If potentially eligible, patients were scheduled for evaluation (n>1200).
Outpatients (n=608) presented for evaluation at the Department of Psychiatry at The University of Texas Southwestern Medical Center at Dallas with the complaint of depression. Inclusion criteria involved the following: (1) DSMIV16
nonpsychotic unipolar MDD; (2) recurrent MDD with clear interepisode recovery (ie, 2 or more episodes of MDD separated by at least 2 months of a return to more-or-less normal functioning); (3) 17-item Hamilton Rating Scale for Depression17
(HRSD-17) score of 16 or higher at initial diagnostic evaluation and at a follow-up; and (4) written informed consent.
Trained evaluators, using the Structured Clinical Interview forDSM-III-R
(SCID outpatient version)18
and strictly applyingDSM-III-R19
criteria for MDD and other disorders, referred 361 patients (59%) for nonprotocol treatment. Exclusion criteria were (1) did not meet criteria for MDD (n=91); (2) MDD not recurrent (n=116); (3) HRSD-17 score less than 16 (n=66); (4) contraindicated medical condition or medication (n=28); (5) exclusionary comorbid psychiatric disorder (MDD with psychotic features, n=2; current alcohol or other drug abuse, n=9; primary sleep, eating, or sexual disorders, n=1 each; and borderline personality disorder, n=7); (5) imminent suicide risk at triage (n=2); or (6) inability to comply with the protocol (n=24). Thirteen patients were lost to follow-up after the initial clinic contact and were mailed referrals.
The remaining 247 patients completed the SCID and supplemental questions to allow evaluation ofDSM-IV diagnoses, entry criteria, and the characteristics described in the .
Pretreatment Demographic and Clinical Characteristics of Outpatients With Recurrent Major Depressive Disorder
A faculty-level diagnostician reassessed eligibility criteria at a follow-up interview. Fifty patients were excluded because they (1) did not meet criteria for MDD (n=13); (2) had nonrecurrent MDD (n=12); (3) had a concurrent medical disorder or received treatment that might cause depressive symptoms (n=11); or (4) had comorbid exclusionary psychiatric disorders (MDD with psychotic features, n=7; delusional disorder, n=1; current alcohol or other drug abuse, n=6). An additional 36 patients were excluded because they (1) had an HRSD-17 score less than 16 at follow-up (n=16); (2) had primary panic disorder with agoraphobia (n=1); (3) had primary bulimia nervosa (n=1);(4) had borderline personality disorder (n=6); (5) could not complete questionnaires or comply with the protocol (n=10); or (6) preferred alternative treatment (n=2).
A total of 161 patients were eligible for the study and 5 refused consent; thus, 156 patients consented to enter A-CT.
Pharmacotherapy was not a study procedure. From entry through follow-up, patients agreed to postpone or report the use of psychotropic medication, nonprotocol psychotherapy, or other psychiatric or psychosocial treatment.
Acute-Phase Cognitive Therapy
Acute-phase cognitive therapy was conducted as described by Beck et al,2
within a 12- to 14-week protocol (twenty 50- to 60-minute individual sessions held twice weekly for the first 8 weeks and once weekly for the last 4 weeks). The therapists completed clinician rating scales. Strategies were focused on symptom reduction but could include relapse prevention.
Five experienced therapists provided CT. Each had completed 1 or more years of CT training, achieving and maintaining Cognitive Therapy Scale24
(CTS) scores of 40 or more before treating any study patients.
An off-site consultant (see the acknowledgments at the end of the article) used the CTS to evaluate competence and provide feedback. Therapists received weekly group supervision.
Randomization to the Experimental Phase
Only responders (no MDD and HRSD-17 score of 9 or less by a blind evaluator) who completed 20 sessions of A-CT and consented to randomization to either C-CT or evaluation only (control) entered the 8-month experimental phase. Responders were randomized using PROC PLAN in SAS statistical software, version 6.04 (SAS Institute Inc, Cary, NC) by strata that included the following: (1) number of episodes (ie, 2 vs ≥3); (2) HRSD-17 score less than 6 and 6 to 9 based on the blind evaluator’s score collected within 7 days of session 20; and (3) double depression (presence or absence ofDSM-IV dysthymia before onset of the presenting episode). Research personnel and patients concealed assignment from blind evaluators.
In both conditions, patients agreed to remain unmedicated and were scheduled for 10 sessions that occurred biweekly for the first 2 months and monthly for the remaining 6 months. The clinician collected self-report questionnaires, assessed diagnostic status according to DSM-IV MDD, recorded any medication use, and completed rating scales. Regardless of diagnostic status, all patients proceeded with C-CT or evaluation until consent was withdrawn or through month 8. All patients were instructed to telephone the evaluator if they became symptomatic between visits. When patients experienced relapse or recurrence, they were referred for additional treatment (eg, pharmacotherapy).
Continuation-Phase Cognitive Therapy
The same therapist provided A-CT and 10 sessions of C-CT as described by Jarrett (unpublished manual available on request) and elaborated by Jarrett and Kraft.15
Patients were taught to use emotional distress or symptoms to trigger coping skills learned in A-CT. The purpose of C-CT is to prevent relapse and recurrence, review strategies associated with effective symptom reduction, maintain skills acquired during A-CT, and develop coping strategies in preparation for identified or anticipated vulnerabilities. Whereas A-CT emphasized reducing symptoms and acquiring skills, C-CT emphasized preventing relapse and recurrence, reducing residual symptoms, and generalizing skills.
Most sessions lasted 60 minutes, although 90 minutes was allowable. Patients received no monetary incentives.
Evaluation Only (Control)
An evaluator who had not provided A-CT conducted 10 assessment visits scheduled at the same frequency as C-CT for 8 months. Prescribed control procedures prohibited the use of CT or other psychosocial interventions before relapse. When patients described psychosocial problems, the evaluator did not intervene. Self-reports and clinician ratings were collected. Sessions lasted approximately 20 to 30 minutes, and patients were paid $25 for each visit.
Longitudinal Follow-up Phase
All consenting patients attended follow-up assessments for 16 months or until they withdrew consent. When clinic assessments were not feasible, evaluations were conducted by telephone. An evaluator followed up the patient monthly for the first 4 months and bimonthly for the remaining 12 months. Procedures were identical to the control cell.
The primary dependent variables were the proportion of DSM-IV
diagnoses of MDD (ie, relapse or recurrence) as specified by an evaluator who was blind to cell assignment and used the Longitudinal Interval Follow-up Evaluation25
(LIFE). Blind evaluations were conducted at (1) the end of A-CT; (2) any time the patient, therapist, or follow-up evaluators suspected relapse or recurrence; (3) early exit; (4) months 4 and 8 of the experimental phase; and (5) months 12 and 24 of follow-up. Assessment for months 13 to 20 was conducted by unblinded evaluators because of the high cost of blind evaluations. If relapse or recurrence was suspected, a blind evaluation occurred.
The following definitions were used to conceptualize and define change points in the course of unipolar MDD.26
Response, the extent of patient response to A-CT, was defined by the blind evaluator within 7 days after session 20 as (1) absence ofDSM-IV MDD and (2) an HRSD-17 score of 9 or less. Remission, when the patient is no longer fully symptomatic, was defined by a diagnostician (ie, therapist, blind evaluator, or other clinic evaluator) specifying for 6 consecutive weeks that (1) DSM-IV criteria for MDD were not met and (2) HRSD-17 score was 6 or less (during the acute phase) or the LIFE Psychiatric Rating Scale (PSR) rating was 1 or 2 (during experimental and follow-up phases). Recovery, the end of an episode, was defined as any project diagnostician declaring for 8 consecutive months that (1) DSM-IV criteria for MDD were not met and (2) HRSD-17 score was 6 or less (during the acute phase) and/or the LIFE PSR rating was 1 or 2 (during experimental and follow-up phases). Relapse, a continuation of the presenting episode, was defined by the blind evaluator as symptoms meetingDSM-IV criteria for MDD (ie, LIFE PSR score of 5 or 6 for 2 weeks) before the criteria for recovery were met. Recurrence, the emergence of a new episode distinct from the presenting episode, was defined by the blind evaluator as meeting DSM-IV criteria for MDD after the criteria for recovery were met.
The hypothesized relapse rates over the 8-month experiment were 47% for control and 19% for C-CT based on early analyses of previous samples.3
A minimum sample size of 72 was necessary to detect a significant difference.27
Recurrence estimates were reported as secondary measures during the 24-month follow-up.
All analyses were of an intention-to-treat strategy (N=84; n for C-CT=41; n for controls=43). The end point in all the survival analyses was either relapse or recurrence. Patients who dropped out or survived were censored. Survival curves and relapse and recurrence rates were estimated using Kaplan-Meier product-limit methods.28
The survival rates for the 2 cells were compared using the log-rank test.29
The Cox proportional hazard regression was used to evaluate the influence of each candidate covariate (age of onset, age, sex, number of episodes, length of current episode, comorbid lifetime diagnoses, and definite Research Diagnostic Criteria21
endogenous diagnosis) as described by Collett.30
Covariates were compared with the null model to determine their influence on relapse over 8 months or on relapse and recurrence over 24 months without regard to condition assignment.
Categorical variables were reported as percent frequency (eg, number and percentage) and continuous variables as mean and SE. Significance was defined as P≤.05; Fisher exact tests (FETs) were 2-tailed.