The Corpus Callosum

Context  Previous studies have found that few chronically depressed patients remit with antidepressant medications alone.

Objective  To determine the role of adjunctive psychotherapy in the treatment of chronically depressed patients with less than complete response to an initial medication trial.

Design  This trial compared 12 weeks of (1) continued pharmacotherapy and augmentation with cognitive behavioral analysis system of psychotherapy (CBASP), (2) continued pharmacotherapy and augmentation with brief supportive psychotherapy (BSP), and (3) continued optimized pharmacotherapy (MEDS) alone. We hypothesized that adding CBASP would produce higher rates of response and remission than adding BSP or continuing MEDS alone.

Setting  Eight academic sites.

Participants  Chronically depressed patients with a current DSM-IV-defined major depressive episode and persistent depressive symptoms for more than 2 years.

Interventions  Phase 1 consisted of open-label, algorithm-guided treatment for 12 weeks based on a history of antidepressant response. Patients not achieving remission received next-step pharmacotherapy options with or without adjunctive psychotherapy (phase 2). Individuals undergoing psychotherapy were randomized to receive either CBASP or BSP stratified by phase 1 response, ie, as nonresponders (NRs) or partial responders (PRs).

Main Outcome Measures  Proportions of remitters, PRs, and NRs and change on Hamilton Scale for Depression (HAM-D) scores.

Results  In all, 808 participants entered phase 1, of which 491 were classified as NRs or PRs and entered phase 2 (200 received CBASP and MEDS, 195 received BSP and MEDS, and 96 received MEDS only). Mean HAM-D scores dropped from 25.9 to 17.7 in NRs and from 15.2 to 9.9 in PRs. No statistically significant differences emerged among the 3 treatment groups in the proportions of phase 2 remission (15.0%), partial response (22.5%), and nonresponse (62.5%) or in changes on HAM-D scores.

Conclusions  Although 37.5% of the participants experienced partial response or remitted in phase 2, neither form of adjunctive psychotherapy significantly improved outcomes over that of a flexible, individualized pharmacotherapy regimen alone. A longitudinal assessment of later-emerging benefits is ongoing.

The good news is that the study was done with participants who were chronically depressed, so if any of them got better, it is a good thing.  about three-eights achieved remission in the first phase, over 12 weeks.  That is not too bad.  In the second phase,  15% achieved remission.  That is OK but hardly great.  Another 22.5% achieved partial response.  So by the end of 24 weeks, about two-thirds of the participants had at least a partial response.  This is fairly typical for a trial of any intervention for depression.  It is reasonably good for a trial that recruited persons with chronic depression. 

However, it was disappointing to the researchers in two respects.  For one, they hypothesized that their cognitive behavioral analysis system of psychotherapy would be shown to be superior to brief supportive therapy.  They did not demonstrate that.  They also did not demonstrate that either form of psychotherapy was better than medication alone. 

One obvious limitation: the second phase was only 12 weeks long.  That is not a lot of time for psychotherapy.  The persons who entered phase two as nonresponders have mean Hamilton Depression scores of 25.9 at the start.  Personally, I would not expect that 12 weeks of psychotherapy would have a strong enough effect to be statistically convincing.  On the other hand, the persons who entered phase two as partial-responders had mean HAM-Ds of 17.7 at the start.  They ended with a mean of 9.9.  I am thinking that once you get down to that level (7 or so is complete remission) that a difference of a few points is going to be hard to see, statistically. 

The study, as published so far, clearly is intended to find out if adding psychotherapy makes a difference in the short run.  While this is interesting, it is the long-term outcome that really matters. 

When treating persons who have chronic depression, I tend to think of medication as being more important than psychotherapy in the short run.*  The real benefit from psychotherapy is converting partial responders to full response, in an intermediate time frame; and in helping to prevent or mitigate relapse, over a longer time frame.  This study does not change my impression, although it does not confirm it, either.  The authors are gong to extend the study and see if a longer period of time enables them to demonstrate an effect. 
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*With many exceptions, of course; I'm referring to general tendencies.