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    1 Comment for this article
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    Where do we go from here?
    Elisabeth Schramm, PhD | Department of Psychiatry and Psychotherapy, University Medical Center Freiburg, Germany
    The recent report of the REVAMP study by Kocsis and colleagues (1) raises an opportunity to compare REVAMP outcomes data with those of Keller et al. (2) on chronically depressed patients. In the latter trial, the combination of psychotherapy (Cognitive Behavioral Analysis System of Psychotherapy: CBASP) and medication turned out to be the most effective treatment for this patient group when compared to both monotherapies. Another important result was that a longer duration of treatment had significant clinical benefits (3). In contrast, the REVAMP protocol mandated treatment with a medication only algorithm for 12 weeks (phase 1), yielding the same low remission rates (22%) reported in the medication monotherapy cell by Keller et al. (2). After an additional 12 weeks of augmentation with either psychotherapy or medication, only an additional 15% of non- and partially responding patients remitted, compared to 42% under combined psycho- and pharmacotherapy after only 12 weeks in the Keller et al. trial. Thus, for chronically depressed patients REVAMP outcomes data reflect little clinical benefit with medication monotherapy, as compared with the combination of CBASP and medication. A design where CBASP alone and/or combined with antidepressants is compared to a placebo treatment or some other specific form of psychotherapy might have offered the field additional, clinically relevant data.
    Another issue is why CBASP worked in one setting (2) but not in the other (1)? First, as the authors of the REVAMP study comment, their sample consisted of patients who were mainly interested in pharmacotherapy and did not (or not completely) respond to it. It is known from other studies (4) that treatment preference has an important impact on outcomes. In our own study (5) with 30 chronically depressed patients randomized to either CBASP or Interpersonal Psychotherapy, we found much higher remission rates for CBASP (78% vs. 23% in IPT). Second, the mean dose of 12.5 sessions of CBASP reported by Kocsis and colleagues may be inadequate, as suggested by a recent meta-analysis of Cuijpers et al. (6). These authors reported that at least 18 treatment sessions are needed for patients with chronic depression to realize optimal effects of psychotherapy. In our study (5), 22 sessions of CBASP resulted in high remission rates.
    For these reasons, it seems premature to dismiss CBASP as an effective treatment option for chronic depression but rather, to continue to study what treatment “dosage” level works the best. Said another way, we need to continue to examine under what treatment circumstances CBASP is more effective. One thing, however, is clear from the REVAMP study data. Chronically depressed patients who do not begin treatment with combined medication and psychotherapy and who are administered only 12.5 hours of psychotherapy are at high risk for poor treatment outcomes.
    Correspondence:
    Elisabeth Schramm, Ph.D., President of the non-profit International CBASP- Network, Department of Psychiatry and Psychotherapy, University Medical Center Freiburg, Germany
    Charles F. Reynolds III, M.D. Western Psychiatric Institute and Clinic, Pittsburgh, PA
    No relevant conflicts of interest.
    (1) Kocsis JH, Gelenberg AJ, Rothbaum BO, Klein DN, Trivedi MH, Manber R, Keller MB, Leon AC, Wisniewski SR, Arnow BA, Markowitz JC, Thase ME; REVAMP Investigators. Cognitive Behavioral Analysis System of Psychotherapy and Brief Supportive Psychotherapy for augmentation of antidepressant nonresponse in chronic depression: the REVAMP Trial. Arch Gen Psychiatry. 2009; 66(11):1178-88.
    (2) Keller MB, McCullough JP, Klein DN, Arnow B, Dunner DL, Gelenberg AJ, Markowitz J, Nemeroff CB, Russell JM, Thase ME, Trivedi M, Zajecka J. A comparison of nefazodone, the Cognitive Behavioral Analysis System of Psychotherapy, and their combination for the treatment of chronic depression. N Engl J Med. 2000; 342(20):1462-1470.
    (3) Gelenberg AJ, Trivedi MH, Rush AJ, Thase ME, Howland R, Klein DN, Kornstein SG, Dunner DL, Markowitz JC, Hirschfeld RM, Keitner GI, Zajecka J, Kocsis JH, Russell JM, Miller I, Manber R, Arnow B, Rothbaum B, Munsaka M, Banks P, Borian FE, & Keller MB. Randomized, placebo-controlled trial of nefazodone maintenance treatment in preventing recurrence in chronic depression. Biol Psychiatry. 2003; 54:806-817.
    (4) Kocsis JH, Leon AC, Markowitz JC, Manber R, Arnow B, Klein DN, Thase ME. Patient preference as a moderator of outcome for chronic forms of major depressive disorder treated with nefazodone, Cognitive Behavioral Analysis System of Psychotherapy, or their combination. J Clin Psychiatry. 2009;70(3):354-61.
    (5) Schramm E, Zobel I, Kech S, v.Calker D, Brakemeier EL, Berger M. IPT in chronic depression: a comparison with the CBASP and with pharmacotherapy. Presentation at the 3rd International Conference of the International Society of IPT. New York: March 2009.
    (6) Cuijpers P, van Straten A, Schuurmans J, van Oppen P, Hollon SD, Andersson, G. Psychotherapy for chronic major depression and dysthymia: A meta-analysis. Clinical Psychology Review. 2009; doi:10.1016/j.cpr.2009.09.003.
    CONFLICT OF INTEREST: None Reported
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    Original Article
    November 2009

    Cognitive Behavioral Analysis System of Psychotherapy and Brief Supportive Psychotherapy for Augmentation of Antidepressant Nonresponse in Chronic Depression: The REVAMP Trial

    Author Affiliations

    Author Affiliations: Departments of Psychiatry, Weill Cornell Medical College, New York, New York (Drs Kocsis, Leon, and Markowitz); University of Wisconsin, and Healthcare Technology Systems, Inc, Madison, Wisconsin (Dr Gelenberg); Emory University School of Medicine, Atlanta, Georgia (Dr Rothbaum); The University of Texas Southwestern Medical Center, Dallas (Dr Trivedi); Epidemiology Data Center, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania (Dr Wisniewski), and University of Pennsylvania School of Medicine and Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania (Dr Thase); Department of Psychology, Stony Brook University, Stony Brook, New York (Dr Klein); Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California (Drs Manber and Arnow); and Department of Psychiatry and Human Behavior, Brown University, Providence, Rhode Island (Dr Keller).

    Arch Gen Psychiatry. 2009;66(11):1178-1188. doi:10.1001/archgenpsychiatry.2009.144
    Abstract

    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.

    Trial Registration  clinicaltrials.gov Identifier: NCT00057551

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