This study found that, among chronically depressed patients who did not fully respond to 12 weeks of MEDS, approximately40%later remitted with 12 more weeks of treatment. Surprisingly, the addition of either of 2 forms of psychotherapy to the pharmacotherapy protocol did not produce significant differences in outcome compared with pharmacotherapy alone. Furthermore, the form of therapy specifically developed for chronic depression—CBASP—added no value over BSP. Our hypothesis that CBASP would produce higher response and remission rates, when compared with adding BSP or continuing MEDS alone, was not supported. These results contradict common clinical practice reflected in the American Psychiatric Association guideline for the treatment of major depression,36
and they also contradict predictions based on previous studies with chronic depression by our group.2,26
What explains these discrepancies? First, sample characteristics may vary across studies. Perhaps there are moderators of response to different psychotherapies, which will be examined in secondary analyses. Second, pharmacotherapy in our previous study2
may not have been optimal. The addition of psychotherapy may have greater benefit in real-world clinical practice. Third, a potentially important difference between this study and that of Keller et al2
was a difference in the mean number of CBASP therapy sessions (16.0 vs 12.5 in the present study). Finally, it is possible that the continued switch/augment strategies used in REVAMP had psychological effects. Our patients may have been less receptive to psychotherapy than were samples in some other studies. The design of the trial ensured that all patients would receive pharmacotherapy throughout, whereas provision of psychotherapy was not guaranteed—a design that may have selected for patients more interested in pharmacotherapy than in psychotherapy. Alternatively, it is conceivable that patients may have become less motivated to engage in psychotherapy after completing 1 or more courses of pharmacotherapy. Another anecdotal impression was that many patients randomized to CBASP and BSP required considerable convincing that psychotherapy was important.47
Future analyses of this sample will examine the effects of patient treatment preferences and the therapeutic alliance. In addition, few studies have examined whether the sequence in which switching/augmentation occurs (ie, pharmacotherapy before psychotherapy vs the opposite) influences treatment outcome.
To our knowledge, the only comparable study of psychotherapy augmentation for patients with major depression is the STAR*D study, which compared the effectiveness of cognitive therapy and pharmacotherapy as second-step strategies for outpatients who had received inadequate benefit from an initial trial of citalopramm hydrobromide.22
Both studies were relatively inclusive, and both used antidepressant pharmacotherapy as the initial treatment. In the STAR*D study, patients who entered a medication algorithm trial were reluctant to consider randomization to psychotherapy. But REVAMP focused specifically on chronic depression, whereas the STAR*D study had a mixed sample. In addition, the STAR*D study offered alternate randomization options for patients who did not wish to receive cognitive therapy. In the STAR*D study, cognitive therapy, both singly and in combination with citalopram, was compared with medication augmentation and switch strategies. Among those who were willing to consider cognitive therapy as a second step, those who received cognitive therapy (alone or in combination with citalopram) had similar response and remission rates to those assigned to medication strategies. Specifically, among patients receiving augmentation with cognitive therapy (n = 65) and pharmacotherapy (n=117), the HAM-D remission rates were 23.1% and 33.3%, respectively. For those who switched to cognitive therapy (n=36) and pharmacotherapy (n=86), the HAM-D remission rates were 30.6% and 26.7%, respectively. For comparison purposes, the last-observation-carried-forward HAM-D remission rates for the 3 treatment groups in REVAMP were 43.0%, 37.9%, and 40.6% for CBASP, BSP, and MEDS, respectively. Overall, neither the STAR*D study nor REVAMP found an advantage for psychotherapy augmentation over MEDS in short-term outcomes.
Taken together with the STAR*D study results, the present findings question the value of psychotherapy augmentation compared with pharmacotherapy augmentation/switch alone. Alternative designs might be more attractive to patients who prefer psychotherapy or might include a component to enhance motivation at the psychotherapy augmentation phase. Perhaps there are subpopulations, such as pregnant or nursing women, individuals who greatly prefer psychotherapy,51
or patients with a history of early adversity,52
for whom psychotherapy augmentation may be an appropriate option. We are currently testing some of these possibilities in moderator analyses using these data.
Limitations of this study include that patients were from academic centers, that the nature of the design and sequencing of interventions may have reduced responsiveness and/or motivation for psychotherapy, and that the duration of psychotherapy may have been too brief for this sample of patients with chronic depression and comorbidities. Like the STAR*D study, the present study used a pragmatic drug treatment design, with broad inclusion criteria and an algorithm of medications. As with the STAR*D study and some other large treatment trials with pragmatic designs,53
the findings have been essentially negative. A speculative point worth investigating is that such designs make differences between treatments hard to demonstrate.
Proponents of cognitive therapy believe that psychotherapy has enduring effects, arguing that patients are taught new skills that they continue to use after the termination of treatment.54,55
We are conducting a follow-up study on the patients in REVAMP to determine whether the combination of CBASP plus MEDS and/or the combination of BSP plus MEDS might have long-term benefits that were not apparent in the short run.