Review of Efficacy Research

There is little literature on CT approaches to drug-resistant depression. Fen-nell and Teasdale (1982) failed to detect a significant effect of CT in five chronic, drug-refractory, depressed outpatients. Antonuccio et al. (1984) applied a psychoeducational group treatment (including relaxation, increasing pleasant activities, cognitive strategies, and social skills) to 10 outpatients with unipolar depression who had not responded to antidepressant medication. All patients continued drug treatment. One patient dropped out of group treatment, four were no longer depressed, two showed some improvement, and three patients were still depressed after psychoeducational group treatment. Improvements were maintained at 9-month follow-up. Miller, Bishop, Norman, and Keitner (1985) examined the effectiveness of a treatment program comprising CT, pharmacotherapy, and short-term hospitalization in six chronic, drug-resistant, depressed females. The approach produced a substantial improvement in the majority of patients. De Jong, Treiber, and Henrich (1988) studied a group of 30 chronically depressed patients who failed to respond to antidepressant drugs. Patients were randomly assigned to an intensive inpatient cognitive-behavioral program, to an inpatient low-intensity milieu therapy, and to a waiting-list control group. Patients treated with the intense cognitive-behavioral program had the better outcome. Cole et al. (1994) treated 16 inpatients who had refractory major depression with CT and found a remission rate of 69%, with a significant decrease in depression ratings. Thase and Howland (1994) reported that after participation in an inpatient cognitive-behavioral program, 17 patients with major depression who were resistant to antidepressant treatment had a 47% remission. In one of our studies (Fava, Savron, Grandi, & Rafanelli, 1997), 19 patients who failed to respond to at least two trials of antidepres-sant drugs of adequate dosage and duration (minimum of 6 weeks) were treated by cognitive-behavioral methods in an open trial. Three patients dropped out of treatment. The remaining 16 subjects displayed a significant decrease in scores on the Clinical Interview of Depression (Paykel, 1985) after therapy. Twelve patients were judged to be in remission at the end of the trial; only one of these patients was found to have relapsed at a 2-year follow-up. Antidepressant drugs were discontinued in 8 of the 12 patients who responded to CT.

PARTIALLY REMITTED DEPRESSION

The notion that the majority of depressed patients experience mild but chronic residual symptoms or recurrence of symptoms after complete remission, a perspective that was well delineated in the 1970s (Weissman, Kasl, & Klerman, 1976), did not receive the attention it deserved in subsequent years. Moreover, the presence of residual symptoms after completion of drug treatment (Fava, 1999; Fava, Fabbri, & Sonino, 2002) or CT (Simons, Murphy, Levine, & Wetzel, 1986; Thase et al., 1992) for depression has been correlated with poor long-term outcome.

The awareness on the one hand that pharmacotherapy is the most cost-effective therapeutic strategy for treatment of the acute phase of a major depression, and on the other hand that cognitive-behavioral approaches are the most valuable intervention for the treatment of residual symptoms and relapse prevention (so that the residual symptomatology does not turn into the prodromal phase of a new depressive episode) is the basis for the sequential administration of pharmacotherapy (as the first ingredient) and psychotherapy (as the second one) according to the stages of the disorder. This sequential approach allows us to use what has been found to be the most effective therapeutic ingredient for each specific phase of the disorder.

The results of several randomized controlled trials, reviewed in detail elsewhere (Fava et al., 2002, 2005) support to the use of a sequential treatment model (pharmacotherapy followed by psychotherapy) to prevent relapse in unipolar depression.

This approach appears to be particularly important in recurrent depression. However, because incomplete recovery from the first lifetime major depressive episode was found to predict a chronic course of illness during a

12-year prospective naturalistic follow-up (Judd et al., 2000), this sequential approach may be indicated whenever substantial residual symptomatology is present.

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