The overall pattern of results observed in this study was that prior psychotherapy, either in the form of cognitive therapy or behavioral activation, had an enduring effect that was at least as efficacious as continuing patients on medications and that held for the prevention of relapse and possibly recurrence. Evidence for this enduring effect was clearer for prior CT than for BA (differences relative to medication withdrawal were typically fully significant for the former and with non-significant trends for the latter), but differences between the two psychosocial interventions never approached statistical significance and were relatively small in magnitude. Although psychotherapy was more expensive to provide initially, and while no formal statistical comparisons of costs among treatment conditions were conducted, the cumulative cost of continued medications proved to be more expensive by the end of the first year of follow-up in this study. To the extent that the effects of psychotherapy endure over time, as is clearly the case for CT and appears to be the case for BA, the cost savings could be considerable.
CT is one of the best-supported treatments for depression (DeRubeis & Crits-Christoph, 1998
), and is the only psychotherapy to date that has demonstrated an enduring effect in the treatment of depression (Hollon, et al., 2006
). For this reason, the indication that BA also may have a comparable enduring effect to CT, but not found for patients successfully treated with medications, is particularly noteworthy. Moreover, these indications build on the findings from the acute phase of the trial, in which both BA and ADM each produced superior results to CT for more severely depressed patients (Dimidjian et al., 2006
If BA does have an enduring effect, how might it achieve this result? BA emphasizes the role of behavior change in overcoming depression, consistent with the BA principles of increasing activity and approaching, rather than avoiding, difficult situations (Martell, et al., 2001
). These ideas are instantiated repeatedly during acute treatment make these ideas highly salient and thus recall at times of potential relapse. Approaching and solving problems during treatment also may fundamentally alter the environmental context in which the person lives, potentially reducing the likelihood of negative events that trigger risk for depression. In effect, BA is implemented in a manner that is intended to both teach coping skills and to reduce future risk. The same is true for CT, which adds an emphasis on cognitive change, but otherwise takes a similar skills-training approach (Coffman et al., 2007
). Both BA and CT had sustained responses that were not significantly different across the current trial. The mechanisms that underlie the enduring effect for CT are still not well understood (Hollon et al., 2006
). Future research is needed to evaluate potentially common and unique mechanisms of change in each approach.
Medication treatment is considered the standard of care for depression in current psychiatric guidelines, with an indefinite length of treatment recommended for those with chronic or recurrent episodes (American Psychiatric Association, 2000
; Frank, et al, 1990
). However, although antidepressant medications generally are safe and efficacious, there is little evidence that they alter the course of the disorder. Even recovered patients are at substantial risk for recurrence once they stop taking medication (Hollon, et al, 2002
). Since depression is often chronic or recurrent (Kessler et al., 2003
) any treatment that has an enduring effect is particularly worthwhile. In the current study, even though we found little evidence of a preventive effect for continuation medication, it was striking how rapidly even recovered patients experienced a recurrence when medications were withdrawn. In contrast, CT provided evidence of sustained benefit, and there were nonsignificant trends in the same direction for BA.
Beyond the enduring clinical benefit of CT and possibly BA, these findings suggest that there may be additional implications for health care delivery with regard to treatment costs. As suggested by Antonuccio and colleagues (1997)
, if psychotherapy truly has enduring effects, it may prove to be more cost-effective than long-term medication treatment. Although more elaborate models for econometric evaluations of treatments exist (Ramsey, Willke, Briggs, Brown, Buxton, et al., 2005
), our relatively simple cost data suggest that the psychosocial interventions may be less expensive over the long run than keeping patients on medication. These findings also were consistent with direct cost estimates recently reported by Hollon and colleagues (2005)
. The current cost estimates were limited in time and place to when and where the study was conducted; however, the findings do suggest that more sophisticated econometric analyses should be considered in future trials.
There are several limitations that are worthy of comment. First, the study was conducted in the setting where BA was first developed, so it is possible that investigator allegiance may have biased the study in favor of that modality. We attempted to ensure that the other modalities were adequately implemented by involving investigators with allegiances to those approaches and appeared to succeed to the extent that we found strong acute effects for ADM and an enduring effect for CT, but replication of the study in other settings would be of significant value to the field. Second, any long-term follow-up study can be biased by differential retention among the treatment groups. Only slightly more than half of the patients originally randomized into active treatment during the acute phase of the trial were eligible for participation in the subsequent follow-up phase, which raises the possibility that differential retention may have biased the results (Klein, 1996
). Although our analyses related to the issue of differential retention did not find any reason for concern, this possibility cannot be dismissed with respect to characteristics that we did not consider.
Third, although the pharmacotherapy conditions were conducted triple blind in the first year of follow-up, we did not assess the success of maintaining the blind. Forth, we conducted more frequent assessments at the beginning of each follow-up year, when patients were being brought off medications, and it is possible that we may have missed later relapses or recurrences. Nonetheless, we made every effort to obtain a continuous record of symptom status over time and patients in each condition were assessed according to the same common schedule. Fifth, there were also a number of constraints on the implementation of the treatments for research purposes that do not reflect usual patterns of clinical practice (cf., Schulberg, Block, Madonia, Scott, Lave, Rodriguez, et al. 1997
). For instance, pharmacotherapists were limited to the use of a single medication throughout the trial and the taper schedule was relatively brief, and psychotherapists were required to terminate treatment at the end of the acute phase and not permitted to offer booster sessions or other ongoing contacts. Increased flexibility of the treatment protocols could be used in future trials to maximize the external validity of findings.
Finally, aspects of the follow-up portion of the study lacked power for some comparisons. We had originally planned to run about half again as many subjects as we did, but the grant was not renewed in the wake of Neil Jacobson’s untimely death, thus limiting the overall sample size. Given these constraints, it is notable that we were able to detect differences between the prior psychotherapies and medications conditions, and even a non-significant trend for BA. Given the limited study power, these results speak both to the promise of BA and to the importance of replication.
Although the current results are promising, they also highlight areas of concern for future research. Although the two psychosocial interventions had enduring effects that were comparable to keeping patients on medications, slightly less than half of the patients initially randomized showed sustained clinical response in the best of treatments and only about a quarter to a third of those patients evidenced sustained recovery across the full two years. Therapists in this trial were highly experienced and worked under conditions often considered ideal, including the provision of frequent supervision by experts. These benefits are rarely available in community settings (Westen, Novonty, & Thompson-Brenner, 2004
). Thus, research on the continued improvement of psychosocial treatments for depression, particularly with a focus on prevention of relapse and recovery, and in settings with higher ecological validity, is warranted (Dozois & Dobson, 2004
Overall, the current results suggest that BA may have an enduring effect that approaches that produced by CT in the treatment of major depression. Prior CT was clearly superior to medication withdrawal and prior BA did almost as well (at the level of a nonsignificant trend). Each was at least as effective as continued medication and at a lower cost. BA also was more efficacious than CT in the acute treatment of more severely depressed patients in this trial (Dimidjian et al., 2006
). In aggregate, these results suggest that behavioral interventions for depression may deserve greater consideration than they have received in recent decades.