James H. Kocsis, MD; Alan J. Gelenberg, MD; Barbara O.
PhD; Daniel N. Klein, PhD; Madhukar H. Trivedi, MD; Rachel Manber, PhD;
Martin B. Keller, MD; Andrew C. Leon, PhD; Steven R. Wisniewski, PhD;
Bruce A. Arnow, PhD; John C. Markowitz, MD; Michael E. Thase, MD; for
the REVAMP Investigators
Arch Gen Psychiatry. 2009;66(11):1178-1188.
Context Previous studies have found that few
chronically depressed patients remit with antidepressant medications
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,
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
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.
*With many exceptions, of course; I’m referring to general tendencies.