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ORIGINAL RESEARCH Key Words: antidepressant, algorithm, pharmacotherapy, psychotherapy, augmentation, remission, response, measurement-based care, personalized care
REVAMP - Research Evaluating the Value of Augmenting Medication with Psychotherapy: Rationale and Design By Madhukar H. Trivedi, James H. Kocsis, Michael E. Thase, David W. Morris, Stephen R. Wisniewski, Andrew C. Leon, Alan J. Gelenberg, Daniel N. Klein, George Niederehe, Alan F. Schatzberg, Philip T. Ninan, Martin B. Keller ABSTRACT ~ This
report presents the rationale, design, and baseline sample characteristics for the REVAMP stu d y. This project is a multisite clinical trial designed to evaluate the efficacy of augmenting sta te-of-the-art pharmacotherapy with psychotherapy in ch ro n ically depressed patients who fail to respond or respond incompletely to an initial trial of antidepressant medication. Background: Chronic forms of major depression disorder (cMDD) are longitudinally continuous forms of major depressive disorder (MDD), and may account for a significant portion of the societal burden of disease associated with M D D. Antidepressant medications and depression-focused psychotherapies have been shown to be ef f e c t ive for cMDD, though the majority fail to ach i eve remission following an ac u te course of tre a t m e n t . There is a pressing need to eva l u a te whether the outcomes o b tained from a well implemented medication algo rithm combined with depre s s i o n focused psy ch o t h erapy can significantly enhance outcomes for cMDD. Ra ti o n a l e : Although there is evidence for the effectiveness of depression-focused psychotherapy for the treatment of cMDD, this is the first prospective, randomized, controlled trial investigating
Trivedi, MD, Morris, PhD, Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA. Kocsis, MD, Leon, PhD, Department of Psychiatry, Weill Medical College of Cornell University, New York, NY, USA. Thase, MD, University of Pennsylvania School of Medicine and Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA. Wisniewski, PhD, Department of Psychiatry, Epidemiology Data Center, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA. Gelenberg, MD, Department of Psychiatry, University of Arizona, Tucson, AZ, USA and presently Healthcare Technology Systems, Madison, WI USA. Klein, PhD, Department of Psychology, Stony Brook University, Stony Brook, NY, USA. Niederehe, PhD, Geriatrics Research Branch, National Institute of Mental Health, Bethesda, MD, USA. Schatzberg, MD, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, CA, USA. Ninan, MD, Department of Psychiatry Mood and Anxiety Disorders Program, Emory University School of Medicine, and presently Wyeth Pharmaceuticals Global Medical Affairs, Neuroscience, Collegeville, PA, USA. Keller, MD, Department of Psychiatry and Human Behavior, Brown University, Providence, RI, USA. To whom correspondence should be addressed: Madhukar H. Trivedi, M.D., Department of Psychiatry, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9119. Phone: (214) 648-0181; Fax: (214) 648-0168; Email:
[email protected].
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p sy ch o t h erapy as an augmentation strategy for patients with cMDD incompletely re s p o n s ive to a trial of antidepressant medica t i o n .Specific Aims: The REVAMP study has three specific aims: first, to compare the ef f i cacy of adding psy ch o t h erapy to a medication ch a n ge versus changing medication alone in chronic depre s s ives with partial response or nonresponse to an initial trial of antidepressant medication; second, to test efficacy of the Cognitive Behav i o ral Analysis System of P sy ch o t h erapy (CBASP) as an au g m e n tation strategy by c o m p a ring it to Support ive Psychotherapy (SP); and third, to test a hypothesized mechanism of therapeutic action of CBASP by examining whether patients receiving CBASP exhibit significantly gre a ter improvements in social problem solving than patients receiving ad j u n c t ive SP or continued m e d i cation alone. As a subsidiary aim, the study also compares the effects of the three randomized treatments on psychosocial outcomes. Design: The stu d y involves two 12-week phases. Du ring Phase 1, patients with cMDD receive antidepressant monotherapy selected ac c o rding to an algorithm that takes into account their prior treatment history. Their pattern of response is evaluate d, those with no response at 8 weeks or less than a full response at 12 weeks ad vance to Phase 2. At the beginning of Phase 2, patients who did not respond to the initial antidepressant monotherapy during Phase 1 are switched to the next medication in the pharm ac o t h erapy algo rithm and ra ndomly assigned in a 2:2:1 ratio to one of t h ree treatment cel l s : 16 sessions of either CBASP (40% of ra n d o m i zations) or SP (40%) added to pharmac o t h erap y, or medication alone (20%) with no added psy ch o t h erap y. Similarl y, patients ach i eving a partial response during Phase 1 have their initial medication augmented with a second antidepressant agent during Phase 2 and are randomly assigned to either CBASP, SP, or medication alone. Patients who ach i eve remission during Phase 1 are not randomized to Phase 2, but ra t h er are monitored monthly for an additional 12 weeks. Comment: Recent sequential treatment studies have provided state-of-the-art knowledge about the need for multiple steps in order to ach i eve remission. The current stu d y, t h erefore, provides an important next step in under s tanding the role of d e p ression-focused psychotherapy in a treatment algorithm so essential in the management of difficult-to-treat depression such as ch ronic forms of major depression. Psychopharmacology Bulletin. 2008;41(4):5–33.
INTRODUCTION AND BACKGROUND De p re s si ve disorders have traditionally been conceptualized as episodic and or remitting conditions. However, over the past two decades it has become apparent that many, if not most, depressed patients have a chronic course, with long periods of full syndromal or residual symptomatology.1–3 As many as 50% of patients with major depressive disorders (MDD) have chronic forms (cMDD) presenting with chronic full syndrome episodes (.2 years), a preexisting history of dysthymia (i.e., double-depression),4,5 or exhibit a pattern of recurrent episodes with significant inter-episode symptomatology.5 P S Y C H O P H A R M A C O L O G Y B U L L E T I N : Vol. 41 · No. 4
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cMDDs are associated with high rates of psychosocial and work impairment,6,7 more frequent suicide attempts and hospitalizations,8 and greater health care utilization.9,10 Due to their frequency of early onset11 and often lifelong course, cMDDs account for a substantial portion of the enormous direct and indirect costs associated with mood disorders.12 Antidepressant medications and depression-focused psychotherapies are effective for the treatment of cMDD. A number of large practical clinical trials have also documented the effectiveness of medication algorithms in “real world” patients with complicated major depressive disorder (MDD).3,13,14 A large multicenter study15 also reported a distinct advantage for the combination of antidepressant medication and depression-focused psychotherapy in a cohort of 681 patients with cMDD. However, this study evaluated only a single medication rather than a treatment algorithm featuring multiple medications along with switch and augmentation adjustments as is common in state-of-the-art clinical pharmacotherapy. In view of the added cost and impracticality of recommending a medication-psychotherapy combination for all patients with cMDD, there is an urgent need to evaluate whether the outcomes obtained from a well implemented medication algorithm can be significantly enhanced by adding depression-focused psychotherapy to the algorithm. The next logical step, therefore, is to explore a stepped approach in which patients start with the less expensive antidepressant monotherapy acutely and add psychotherapy as treatment response dictates. Moreover, Schatzberg et al. have provided support for the notion that many pharmacotherapy nonresponders may respond to at least some forms of psychotherapy.16,17
7 Trivedi, Kocsis, Thase, et al.
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