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A Comparison of Nefazodone, the Cognitive Behavioral-Analysis System of Psychotherapy, and Their Combination for the Treatment of Chronic Depression
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BACKGROUND: Patients with chronic forms of major depression are difficult to treat, and the relative efficacy of medications and psychotherapy is uncertain. METHODS: We randomly assigned 681 adults with a chronic nonpsychotic major depressive disorder to 12 weeks of outpatient treatment with nefazodone (maximal dose, 600 mg per day), the cognitive behavioral-analysis system of psychotherapy (16 to 20 sessions), or both. At base line, all patients had scores of at least 20 on the 24-item Hamilton Rating Scale for Depression (indicating clinically significant depression). Remission was defined as a score of 8 or less at weeks 10 and 12. For patients who did not have remission, a satisfactory response was defined as a reduction in the score by at least 50 percent from base line and a score of 15 or less. Raters were unaware of the patients' treatment assignments. RESULTS: Of the 681 patients, 662 attended at least one treatment session and were included in the analysis of response. The overall rate of response (both remission and satisfactory response) was 48 percent in both the nefazodone group and in the psychotherapy group, as compared with 73 percent in the combined-treatment group. (P<0.001 for both comparisons). Among the 519 subjects who completed the study, the rates of response were 55 percent in the nefazodone group and 52 percent in the psychotherapy group, as compared with 85 percent in the combined-treatment group (P<0.001 for both comparisons). The rates of withdrawal were similar in the three groups. Adverse events in the nefazodone group 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 forms of major depression have a response to short-term treatment with either nefazodone or a cognitive behavioral-analysis system of psychotherapy, the combination of the two is significantly more efficacious than either treatment alone.
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“Both psychotherapies emphasize the importance of learning to resolve interpersonal problems as crucial for overcoming chronic depression.”
From Helpful and hindering factors for remission in dysthymia and panic disorder at 9-year follow-up: A mixed methods study (2008) · cites this paper as [44]
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“Two empirically supported psychotherapies are designed for the treatment of chronic depression and dysthymia, i.e. interpersonal psychotherapy (IPT) and cognitive behavioural analysis system of psychotherapy (CBASP) [43,44].”
From Helpful and hindering factors for remission in dysthymia and panic disorder at 9-year follow-up: A mixed methods study (2008) · cites this paper as [44]
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“Multiple studies have demonstrated the efficacy of CBASP in reducing symptoms of PDD (Keller et al. 2000; Negt et al. 2016; Sabaß et al. 2018; Schramm et al. 2017).”
From Reciprocal Dynamics of Therapeutic Alliance and Depressive Symptoms in Inpatient Cognitive Behavioural Analysis System of Psychotherapy: The Role of Attachment Insecurity. (2025) · cites this paper as Keller et al. 2000
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“although some evidence from clinical trials in adults does suggest an acute advantage of combination over individually administered treatments (Keller et al, 2000)”
From Using an Experimental Medicine Model to Explore Combination Effects of Pharmacological and Cognitive Interventions for Depression and Anxiety (2011) · cites this paper as Keller et al, 2000
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Rubin, R. T. (2000) · New England Journal of Medicine · doi:10.1056/nejm200010053431410 · Cited by 2
Narod, S. A. (2001) · New England Journal of Medicine · doi:10.1056/nejm200103223441215 · Cited by 2
Use of psychotherapy in treatment-resistant depression
Moukaddam, N., Hashmi, A. M., & Nguyen, P. (2016) · Psychiatric Annals · doi:10.3928/00485713-20160217-01 · Cited by 1
Metadata
- Authors
- Keller, M. B., McCullough, J. P., Klein, D. N., Arnow, B., Dunner, D. L., Gelenberg, A. J., Markowitz, J. C., Nemeroff, C. B., Russell, J. M., Thase, M. E., Trivedi, M. H., Blalock, J. A., Borian, F. E., Jody, D. N., DeBattista, C., Koran, L. M., Schatzberg, A. F., Fawcett, J., Hirschfeld, R. M. A., Keitner, G., Miller, I., Kocsis, J. H., Kornstein, S. G., Manber, R., Ninan, P. T., Rothbaum, B., Rush, A. J., Vivian, D., & Zajecka, J.
- Affiliations
- Brown University (US)
- Virginia Commonwealth University (US)
- State University of New York (US)
- Stanford University (US)
- University of Arizona (US)
- Cornell University (US)
- Emory University (US)
- The University of Texas Medical Branch at Galveston (US)
- University of Pittsburgh (US)
- The University of Texas Southwestern Medical Center (US)
- Rush University Medical Center (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2000-05-18
- Volume
- 342
- Issue
- 20
- Pages
- 1462-1470
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2326556724
- Cited by
- 1,331
- References
- 34
- Citations by year
- 2026: 14 · 2025: 10 · 2024: 17 · 2023: 17 · 2022: 22 · 2021: 25 · 2020: 35 · 2019: 29 · 2018: 24 · 2017: 39 · 2016: 51 · 2015: 59 · 2014: 58 · 2013: 63 · 2012: 67
- FWCI
- 49.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- VCU Scholars Compass (Virginia Commonwealth University) (submittedVersion)
- Funders
- National Institute of Mental Health (U01MH061590)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Social Sciences › Psychology › Clinical Psychology › Psychotherapy Techniques and Applications
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- nefazodone, CBASP, antidepressant efficacy, treatment response, remission, adverse drug reactions
- MeSH terms
- Adult, Behavior Therapy, Chronic Disease, Combined Modality Therapy, Depressive Disorder, Female, Humans, Male, Piperazines, Triazoles, Cognitive Behavioral Therapy, Treatment Outcome, Antidepressive Agents, Second-Generation
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