Randomized, placebo-controlled trial of nefazodone maintenance treatment in preventing recurrence in chronic depression

Alan J. Gelenberg, Madhukar H. Trivedi, A. John Rush, Michael E. Thase, Robert Howland, Daniel N. Klein, Susan G. Kornstein, David L. Dunner, John C. Markowitz, Robert M A Hirschfeld, Gabor I. Keitner, John Zajecka, James H. Kocsis, James M. Russell, Ivan Miller, Rachel Manber, Bruce Arnow, Barbara Rothbaum, Melvin Munsaka, Phillip BanksFrances E. Borian, Martin B. Keller

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Background: Maintenance treatment to prevent recurrences is recommended for chronic forms of major depressive disorder (MDD), but few studies have examined maintenance efficacy of antidepressants with chronic MDD. This randomized, placebo-controlled study of the efficacy and safety of nefazodone in preventing recurrence was conducted for patients with chronic MDD. Methods: A total of 165 outpatients with chronic, nonpsychotic MDD, MDD plus dysthymic disorder ("double-depression"), or recurrent MDD with incomplete inter-episode recovery, who achieved and maintained a clinical response during acute and continuation treatment with either nefazodone alone or nefazodone combined with psychotherapy, were randomized to 52 weeks of double-blind nefazodone (maximum dose 600 mg/day) or placebo. The occurrence of major depressive episodes during maintenance treatment was assessed with the 24-item Hamilton Rating Scale for Depression, a DSM-IV MDD checklist, and a blinded review of symptom exacerbations by a consensus committee of research clinicians. Results: Application of a competing-risk model that estimated the conditional probability of recurrence among those patients remaining on active therapy revealed a significant (p = .043) difference between nefazodone (n = 76) and placebo (n = 74) when the latter part of the 1-year maintenance period was emphasized. At the end of 1 year, the conditional probability of recurrence was 30.3% for nefazodone-treated patients, compared with 47.5% for placebo-treated patients. Prior concomitant psychotherapy during acute/continuation treatment, although enhancing the initial response, was not associated with lower recurrence rates. Discontinuations due to adverse events were relatively low for both nefazodone (5.3%) and placebo (4.8%). Somnolence was significantly greater among the patients taking active medication (15.4%), compared with placebo (4.6%). Conclusions: Nefazodone is well-tolerated and is an effective maintenance therapy for chronic forms of MDD.

Original languageEnglish (US)
Pages (from-to)806-817
Number of pages12
JournalBiological Psychiatry
Volume54
Issue number8
DOIs
StatePublished - Oct 15 2003

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Major Depressive Disorder
Randomized Controlled Trials
Placebos
Depression
Recurrence
Therapeutics
Psychotherapy
Dysthymic Disorder
Maintenance
nefazodone
Checklist
Diagnostic and Statistical Manual of Mental Disorders
Antidepressive Agents
Consensus
Outpatients
Safety
Research

Keywords

  • Chronic major depression
  • Combined treatment
  • Maintenance treatment
  • Nefazodone
  • Recurrence

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Gelenberg, A. J., Trivedi, M. H., Rush, A. J., Thase, M. E., Howland, R., Klein, D. N., ... Keller, M. B. (2003). Randomized, placebo-controlled trial of nefazodone maintenance treatment in preventing recurrence in chronic depression. Biological Psychiatry, 54(8), 806-817. https://doi.org/10.1016/S0006-3223(02)01971-6

Randomized, placebo-controlled trial of nefazodone maintenance treatment in preventing recurrence in chronic depression. / Gelenberg, Alan J.; Trivedi, Madhukar H.; Rush, A. John; Thase, Michael E.; Howland, Robert; Klein, Daniel N.; Kornstein, Susan G.; Dunner, David L.; Markowitz, John C.; Hirschfeld, Robert M A; Keitner, Gabor I.; Zajecka, John; Kocsis, James H.; Russell, James M.; Miller, Ivan; Manber, Rachel; Arnow, Bruce; Rothbaum, Barbara; Munsaka, Melvin; Banks, Phillip; Borian, Frances E.; Keller, Martin B.

In: Biological Psychiatry, Vol. 54, No. 8, 15.10.2003, p. 806-817.

Research output: Contribution to journalArticle

Gelenberg, AJ, Trivedi, MH, Rush, AJ, Thase, ME, Howland, R, Klein, DN, Kornstein, SG, Dunner, DL, Markowitz, JC, Hirschfeld, RMA, Keitner, GI, Zajecka, J, Kocsis, JH, Russell, JM, Miller, I, Manber, R, Arnow, B, Rothbaum, B, Munsaka, M, Banks, P, Borian, FE & Keller, MB 2003, 'Randomized, placebo-controlled trial of nefazodone maintenance treatment in preventing recurrence in chronic depression', Biological Psychiatry, vol. 54, no. 8, pp. 806-817. https://doi.org/10.1016/S0006-3223(02)01971-6
Gelenberg, Alan J. ; Trivedi, Madhukar H. ; Rush, A. John ; Thase, Michael E. ; Howland, Robert ; Klein, Daniel N. ; Kornstein, Susan G. ; Dunner, David L. ; Markowitz, John C. ; Hirschfeld, Robert M A ; Keitner, Gabor I. ; Zajecka, John ; Kocsis, James H. ; Russell, James M. ; Miller, Ivan ; Manber, Rachel ; Arnow, Bruce ; Rothbaum, Barbara ; Munsaka, Melvin ; Banks, Phillip ; Borian, Frances E. ; Keller, Martin B. / Randomized, placebo-controlled trial of nefazodone maintenance treatment in preventing recurrence in chronic depression. In: Biological Psychiatry. 2003 ; Vol. 54, No. 8. pp. 806-817.
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T1 - Randomized, placebo-controlled trial of nefazodone maintenance treatment in preventing recurrence in chronic depression

AU - Gelenberg, Alan J.

AU - Trivedi, Madhukar H.

AU - Rush, A. John

AU - Thase, Michael E.

AU - Howland, Robert

AU - Klein, Daniel N.

AU - Kornstein, Susan G.

AU - Dunner, David L.

AU - Markowitz, John C.

AU - Hirschfeld, Robert M A

AU - Keitner, Gabor I.

AU - Zajecka, John

AU - Kocsis, James H.

AU - Russell, James M.

AU - Miller, Ivan

AU - Manber, Rachel

AU - Arnow, Bruce

AU - Rothbaum, Barbara

AU - Munsaka, Melvin

AU - Banks, Phillip

AU - Borian, Frances E.

AU - Keller, Martin B.

PY - 2003/10/15

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N2 - Background: Maintenance treatment to prevent recurrences is recommended for chronic forms of major depressive disorder (MDD), but few studies have examined maintenance efficacy of antidepressants with chronic MDD. This randomized, placebo-controlled study of the efficacy and safety of nefazodone in preventing recurrence was conducted for patients with chronic MDD. Methods: A total of 165 outpatients with chronic, nonpsychotic MDD, MDD plus dysthymic disorder ("double-depression"), or recurrent MDD with incomplete inter-episode recovery, who achieved and maintained a clinical response during acute and continuation treatment with either nefazodone alone or nefazodone combined with psychotherapy, were randomized to 52 weeks of double-blind nefazodone (maximum dose 600 mg/day) or placebo. The occurrence of major depressive episodes during maintenance treatment was assessed with the 24-item Hamilton Rating Scale for Depression, a DSM-IV MDD checklist, and a blinded review of symptom exacerbations by a consensus committee of research clinicians. Results: Application of a competing-risk model that estimated the conditional probability of recurrence among those patients remaining on active therapy revealed a significant (p = .043) difference between nefazodone (n = 76) and placebo (n = 74) when the latter part of the 1-year maintenance period was emphasized. At the end of 1 year, the conditional probability of recurrence was 30.3% for nefazodone-treated patients, compared with 47.5% for placebo-treated patients. Prior concomitant psychotherapy during acute/continuation treatment, although enhancing the initial response, was not associated with lower recurrence rates. Discontinuations due to adverse events were relatively low for both nefazodone (5.3%) and placebo (4.8%). Somnolence was significantly greater among the patients taking active medication (15.4%), compared with placebo (4.6%). Conclusions: Nefazodone is well-tolerated and is an effective maintenance therapy for chronic forms of MDD.

AB - Background: Maintenance treatment to prevent recurrences is recommended for chronic forms of major depressive disorder (MDD), but few studies have examined maintenance efficacy of antidepressants with chronic MDD. This randomized, placebo-controlled study of the efficacy and safety of nefazodone in preventing recurrence was conducted for patients with chronic MDD. Methods: A total of 165 outpatients with chronic, nonpsychotic MDD, MDD plus dysthymic disorder ("double-depression"), or recurrent MDD with incomplete inter-episode recovery, who achieved and maintained a clinical response during acute and continuation treatment with either nefazodone alone or nefazodone combined with psychotherapy, were randomized to 52 weeks of double-blind nefazodone (maximum dose 600 mg/day) or placebo. The occurrence of major depressive episodes during maintenance treatment was assessed with the 24-item Hamilton Rating Scale for Depression, a DSM-IV MDD checklist, and a blinded review of symptom exacerbations by a consensus committee of research clinicians. Results: Application of a competing-risk model that estimated the conditional probability of recurrence among those patients remaining on active therapy revealed a significant (p = .043) difference between nefazodone (n = 76) and placebo (n = 74) when the latter part of the 1-year maintenance period was emphasized. At the end of 1 year, the conditional probability of recurrence was 30.3% for nefazodone-treated patients, compared with 47.5% for placebo-treated patients. Prior concomitant psychotherapy during acute/continuation treatment, although enhancing the initial response, was not associated with lower recurrence rates. Discontinuations due to adverse events were relatively low for both nefazodone (5.3%) and placebo (4.8%). Somnolence was significantly greater among the patients taking active medication (15.4%), compared with placebo (4.6%). Conclusions: Nefazodone is well-tolerated and is an effective maintenance therapy for chronic forms of MDD.

KW - Chronic major depression

KW - Combined treatment

KW - Maintenance treatment

KW - Nefazodone

KW - Recurrence

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