A Comparison of Nefazodone, the Cognitive Behavioral-Analysis System of Psychotherapy, and Their Combination for the Treatment of Chronic Depression
Martin B. Keller, M.D., James P. McCullough, Ph.D., Daniel N. Klein, Ph.D., Bruce Arnow, Ph.D., David L. Dunner, M.D., Alan J. Gelenberg, M.D., John C. Markowitz, M.D., Charles B. Nemeroff, M.D., Ph.D., James M. Russell, M.D., Michael E. Thase, M.D., Madhukar H. Trivedi, M.D., and John Zajecka, M.D.
Background Patients with chronic forms of major depression aredifficult to treat, and the relative efficacy of medicationsand psychotherapy is uncertain.
Methods We randomly assigned 681 adults with a chronic nonpsychoticmajor depressive disorder to 12 weeks of outpatient treatmentwith nefazodone (maximal dose, 600 mg per day), the cognitivebehavioral-analysis system of psychotherapy (16 to 20 sessions),or both. At base line, all patients had scores of at least 20on the 24-item Hamilton Rating Scale for Depression (indicatingclinically significant depression). Remission was defined asa score of 8 or less at weeks 10 and 12. For patients who didnot have remission, a satisfactory response was defined as areduction in the score by at least 50 percent from base lineand a score of 15 or less. Raters were unaware of the patients'treatment assignments.
Results Of the 681 patients, 662 attended at least one treatmentsession and were included in the analysis of response. The overallrate of response (both remission and satisfactory response)was 48 percent in both the nefazodone group and the psychotherapygroup, as compared with 73 percent in the combined-treatmentgroup (P<0.001 for both comparisons). Among the 519 subjectswho completed the study, the rates of response were 55 percentin the nefazodone group and 52 percent in the psychotherapygroup, as compared with 85 percent in the combined-treatmentgroup (P<0.001 for both comparisons). The rates of withdrawalwere similar in the three groups. Adverse events in the nefazodonegroup were consistent with the known side effects of the drug(e.g., headache, somnolence, dry mouth, nausea, and dizziness).
Conclusions Although about half of patients with chronic formsof major depression have a response to short-term treatmentwith either nefazodone or a cognitive behavioral-analysis systemof psychotherapy, the combination of the two is significantlymore efficacious than either treatment alone.
Source Information
From the Department of Psychiatry, Brown University, Providence, R.I. (M.B.K.); the Unipolar Mood Disorders Institute, Department of Psychology, Virginia Commonwealth University, Richmond (J.P.M.); the Department of Psychology, State University of New York at Stony Brook, Stony Brook (D.N.K.); the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif. (B.A.); the Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle (D.L.D.); the Department of Psychiatry, University of Arizona, Tucson (A.J.G.); the Department of Psychiatry, Cornell University Medical College, New York (J.C.M.); the Department of Psychiatry, Emory University School of Medicine, Atlanta (C.B.N.); the Department of Psychiatry and Behavioral Sciences, University of Texas Medical Branch at Galveston, Galveston (J.M.R.); the Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh, Pittsburgh (M.E.T.); the Department of Psychiatry, University of Texas Southwestern Medical Center at Dallas, Dallas (M.H.T.); and the Department of Psychiatry, RushPresbyterianSt. Luke's Medical Center, Chicago (J.Z.). Other authors were Janice A. Blalock, Ph.D. (M.D. Anderson Cancer Center, Houston); Frances E. Borian, R.N., and Darlene N. Jody, M.D. (Bristol-Myers Squibb, Plainsboro, N.J.); Charles DeBattista, D.M.H., M.D., Lorrin M. Koran, M.D., and Alan F. Schatzberg, M.D. (Stanford University, Stanford, Calif.); Jan Fawcett, M.D. (RushPresbyterianSt. Luke's Medical Center, Chicago); Robert M.A. Hirschfeld, M.D. (University of Texas Medical Branch at Galveston, Galveston); Gabor Keitner, M.D., and Ivan Miller, Ph.D. (Brown University, Providence); James H. Kocsis, M.D. (Cornell University Medical College, New York); Susan G. Kornstein, M.D. (Virginia Commonwealth University, Richmond); Rachel Manber, Ph.D. (University of Arizona, Tucson); Philip T. Ninan, M.D., and Barbara Rothbaum, Ph.D. (Emory University School of Medicine, Atlanta); A. John Rush, M.D. (University of Texas Southwestern Medical Center at Dallas, Dallas); and Dina Vivian, Ph.D. (State University of New York at Stony Brook, Stony Brook).
Address reprint requests to Dr. Keller at the Department of Psychiatry and Human Behavior, Brown University, 345 Blackstone Blvd., Providence, RI 02906.
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