The Prevention of Recurrent Episodes of Depression with Venlafaxine for Two Years (PREVENT) study

Outcomes from the 2-year and combined maintenance phases

Martin B. Keller, Madhukar H. Trivedi, Michael E. Thase, Richard C. Shelton, Susan G. Kornstein, Charles B. Nemeroff, Edward S. Friedman, Alan J. Gelenberg, James H. Kocsis, David L. Dunner, Robert M A Hirschfeld, Anthony J. Rothschild, James M. Ferguson, Alan F. Schatzberg, John M. Zajecka, Ronald D. Pedersen, Bing Yan, Saeeduddin Ahmed, Jeff Musgnung, Philip T. Ninan

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Objective: To report second-year results from the 2-year maintenance phase of a long-term study to evaluate the efficacy and safety of venlafaxine extended release (ER) in preventing recurrence of depression. Method: Outpatients with recurrent unipolar depression (DSM-IV criteria; N = 1096) were randomly assigned in a 3:1 ratio to 10 weeks of treatment with venlafaxine ER or fluoxetine. Responders (17-item Hamilton Rating Scale for Depression [HAM-D17] total score ≤ 12 and ≥ 50% decrease from baseline) entered a 6-month, double-blind continuation phase on the same medication. Continuation-phase responders were enrolled into maintenance treatment consisting of 2 consecutive 12-month phases. At the start of each maintenance phase, venlafaxine ER responders were randomly assigned to receive double-blind treatment with venlafaxine ER or placebo, and fluoxetine responders were continued for each period. The second 12-month maintenance phase compared the time to recurrence of depression with venlafaxine ER (75 to 300 mg/day) versus placebo as the primary efficacy measure. The primary definition of recurrence was a HAM-D17 total score > 12 and < 50% reduction from baseline (acute phase) at 2 consecutive visits or at the last valid visit prior to discontinuation. The time to recurrence was evaluated using Kaplan-Meier methods and compared between the venlafaxine ER and placebo groups using log-rank tests. Secondary outcome measures included rates of response and remission (defined as HAM-D17 ≤ 7). The study was conducted from December 2000 through July 2005. Results: The cumulative probabilities of recurrence through 12 months in the venlafaxine ER (N = 43) and placebo (N = 40) groups were 8.0% (95% CI = 0.0 to 16.8) and 44.8% (95% CI = 27.6 to 62.0), respectively (p < .001). At month 12, using last-observation-carried-forward analysis, the rate of response or remission was significantly higher in the venlafaxine ER group (93%) than in the placebo group (63%; p = .002). Overall discontinuation rates were 28% and 63% in the venlafaxine ER and placebo groups, respectively. Adverse events were the primary reason for discontinuation for 1 patient (2%) in the venlafaxine ER group and 4 (10%) in the placebo group. An analysis of the combined maintenance phases, which compared the risk of recurrence over 24 months for patients assigned to venlafaxine ER (N = 129) or placebo (N = 129) for the first maintenance phase, showed a significantly greater cumulative probability of recurrence through 24 months for the placebo group (47.3% [95% CI = 36.4 to 58.2]) than for the venlafaxine ER group (28.5% [95% CI = 18.3 to 38.7]; p = .005). Conclusion: In this study, an additional 12 months of maintenance therapy with venlafaxine ER was effective in preventing recurrence of depression in patients who had been responders to venlafaxine ER after acute (10 weeks), continuation (6 months), and initial maintenance (12 months) therapy. Trial Registration: ClinicalTrials.gov identifier NCT00046020 (http://www.clinicaltrials.gov).

Original languageEnglish (US)
Pages (from-to)1246-1256
Number of pages11
JournalJournal of Clinical Psychiatry
Volume68
Issue number8
StatePublished - Aug 2007

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Maintenance
Outcome Assessment (Health Care)
Depression
Placebos
Recurrence
Fluoxetine
Venlafaxine Hydrochloride
Therapeutics
Depressive Disorder
Diagnostic and Statistical Manual of Mental Disorders
Outpatients
Observation
Safety

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Clinical Psychology

Cite this

Keller, M. B., Trivedi, M. H., Thase, M. E., Shelton, R. C., Kornstein, S. G., Nemeroff, C. B., ... Ninan, P. T. (2007). The Prevention of Recurrent Episodes of Depression with Venlafaxine for Two Years (PREVENT) study: Outcomes from the 2-year and combined maintenance phases. Journal of Clinical Psychiatry, 68(8), 1246-1256.

The Prevention of Recurrent Episodes of Depression with Venlafaxine for Two Years (PREVENT) study : Outcomes from the 2-year and combined maintenance phases. / Keller, Martin B.; Trivedi, Madhukar H.; Thase, Michael E.; Shelton, Richard C.; Kornstein, Susan G.; Nemeroff, Charles B.; Friedman, Edward S.; Gelenberg, Alan J.; Kocsis, James H.; Dunner, David L.; Hirschfeld, Robert M A; Rothschild, Anthony J.; Ferguson, James M.; Schatzberg, Alan F.; Zajecka, John M.; Pedersen, Ronald D.; Yan, Bing; Ahmed, Saeeduddin; Musgnung, Jeff; Ninan, Philip T.

In: Journal of Clinical Psychiatry, Vol. 68, No. 8, 08.2007, p. 1246-1256.

Research output: Contribution to journalArticle

Keller, MB, Trivedi, MH, Thase, ME, Shelton, RC, Kornstein, SG, Nemeroff, CB, Friedman, ES, Gelenberg, AJ, Kocsis, JH, Dunner, DL, Hirschfeld, RMA, Rothschild, AJ, Ferguson, JM, Schatzberg, AF, Zajecka, JM, Pedersen, RD, Yan, B, Ahmed, S, Musgnung, J & Ninan, PT 2007, 'The Prevention of Recurrent Episodes of Depression with Venlafaxine for Two Years (PREVENT) study: Outcomes from the 2-year and combined maintenance phases', Journal of Clinical Psychiatry, vol. 68, no. 8, pp. 1246-1256.
Keller, Martin B. ; Trivedi, Madhukar H. ; Thase, Michael E. ; Shelton, Richard C. ; Kornstein, Susan G. ; Nemeroff, Charles B. ; Friedman, Edward S. ; Gelenberg, Alan J. ; Kocsis, James H. ; Dunner, David L. ; Hirschfeld, Robert M A ; Rothschild, Anthony J. ; Ferguson, James M. ; Schatzberg, Alan F. ; Zajecka, John M. ; Pedersen, Ronald D. ; Yan, Bing ; Ahmed, Saeeduddin ; Musgnung, Jeff ; Ninan, Philip T. / The Prevention of Recurrent Episodes of Depression with Venlafaxine for Two Years (PREVENT) study : Outcomes from the 2-year and combined maintenance phases. In: Journal of Clinical Psychiatry. 2007 ; Vol. 68, No. 8. pp. 1246-1256.
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title = "The Prevention of Recurrent Episodes of Depression with Venlafaxine for Two Years (PREVENT) study: Outcomes from the 2-year and combined maintenance phases",
abstract = "Objective: To report second-year results from the 2-year maintenance phase of a long-term study to evaluate the efficacy and safety of venlafaxine extended release (ER) in preventing recurrence of depression. Method: Outpatients with recurrent unipolar depression (DSM-IV criteria; N = 1096) were randomly assigned in a 3:1 ratio to 10 weeks of treatment with venlafaxine ER or fluoxetine. Responders (17-item Hamilton Rating Scale for Depression [HAM-D17] total score ≤ 12 and ≥ 50{\%} decrease from baseline) entered a 6-month, double-blind continuation phase on the same medication. Continuation-phase responders were enrolled into maintenance treatment consisting of 2 consecutive 12-month phases. At the start of each maintenance phase, venlafaxine ER responders were randomly assigned to receive double-blind treatment with venlafaxine ER or placebo, and fluoxetine responders were continued for each period. The second 12-month maintenance phase compared the time to recurrence of depression with venlafaxine ER (75 to 300 mg/day) versus placebo as the primary efficacy measure. The primary definition of recurrence was a HAM-D17 total score > 12 and < 50{\%} reduction from baseline (acute phase) at 2 consecutive visits or at the last valid visit prior to discontinuation. The time to recurrence was evaluated using Kaplan-Meier methods and compared between the venlafaxine ER and placebo groups using log-rank tests. Secondary outcome measures included rates of response and remission (defined as HAM-D17 ≤ 7). The study was conducted from December 2000 through July 2005. Results: The cumulative probabilities of recurrence through 12 months in the venlafaxine ER (N = 43) and placebo (N = 40) groups were 8.0{\%} (95{\%} CI = 0.0 to 16.8) and 44.8{\%} (95{\%} CI = 27.6 to 62.0), respectively (p < .001). At month 12, using last-observation-carried-forward analysis, the rate of response or remission was significantly higher in the venlafaxine ER group (93{\%}) than in the placebo group (63{\%}; p = .002). Overall discontinuation rates were 28{\%} and 63{\%} in the venlafaxine ER and placebo groups, respectively. Adverse events were the primary reason for discontinuation for 1 patient (2{\%}) in the venlafaxine ER group and 4 (10{\%}) in the placebo group. An analysis of the combined maintenance phases, which compared the risk of recurrence over 24 months for patients assigned to venlafaxine ER (N = 129) or placebo (N = 129) for the first maintenance phase, showed a significantly greater cumulative probability of recurrence through 24 months for the placebo group (47.3{\%} [95{\%} CI = 36.4 to 58.2]) than for the venlafaxine ER group (28.5{\%} [95{\%} CI = 18.3 to 38.7]; p = .005). Conclusion: In this study, an additional 12 months of maintenance therapy with venlafaxine ER was effective in preventing recurrence of depression in patients who had been responders to venlafaxine ER after acute (10 weeks), continuation (6 months), and initial maintenance (12 months) therapy. Trial Registration: ClinicalTrials.gov identifier NCT00046020 (http://www.clinicaltrials.gov).",
author = "Keller, {Martin B.} and Trivedi, {Madhukar H.} and Thase, {Michael E.} and Shelton, {Richard C.} and Kornstein, {Susan G.} and Nemeroff, {Charles B.} and Friedman, {Edward S.} and Gelenberg, {Alan J.} and Kocsis, {James H.} and Dunner, {David L.} and Hirschfeld, {Robert M A} and Rothschild, {Anthony J.} and Ferguson, {James M.} and Schatzberg, {Alan F.} and Zajecka, {John M.} and Pedersen, {Ronald D.} and Bing Yan and Saeeduddin Ahmed and Jeff Musgnung and Ninan, {Philip T.}",
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TY - JOUR

T1 - The Prevention of Recurrent Episodes of Depression with Venlafaxine for Two Years (PREVENT) study

T2 - Outcomes from the 2-year and combined maintenance phases

AU - Keller, Martin B.

AU - Trivedi, Madhukar H.

AU - Thase, Michael E.

AU - Shelton, Richard C.

AU - Kornstein, Susan G.

AU - Nemeroff, Charles B.

AU - Friedman, Edward S.

AU - Gelenberg, Alan J.

AU - Kocsis, James H.

AU - Dunner, David L.

AU - Hirschfeld, Robert M A

AU - Rothschild, Anthony J.

AU - Ferguson, James M.

AU - Schatzberg, Alan F.

AU - Zajecka, John M.

AU - Pedersen, Ronald D.

AU - Yan, Bing

AU - Ahmed, Saeeduddin

AU - Musgnung, Jeff

AU - Ninan, Philip T.

PY - 2007/8

Y1 - 2007/8

N2 - Objective: To report second-year results from the 2-year maintenance phase of a long-term study to evaluate the efficacy and safety of venlafaxine extended release (ER) in preventing recurrence of depression. Method: Outpatients with recurrent unipolar depression (DSM-IV criteria; N = 1096) were randomly assigned in a 3:1 ratio to 10 weeks of treatment with venlafaxine ER or fluoxetine. Responders (17-item Hamilton Rating Scale for Depression [HAM-D17] total score ≤ 12 and ≥ 50% decrease from baseline) entered a 6-month, double-blind continuation phase on the same medication. Continuation-phase responders were enrolled into maintenance treatment consisting of 2 consecutive 12-month phases. At the start of each maintenance phase, venlafaxine ER responders were randomly assigned to receive double-blind treatment with venlafaxine ER or placebo, and fluoxetine responders were continued for each period. The second 12-month maintenance phase compared the time to recurrence of depression with venlafaxine ER (75 to 300 mg/day) versus placebo as the primary efficacy measure. The primary definition of recurrence was a HAM-D17 total score > 12 and < 50% reduction from baseline (acute phase) at 2 consecutive visits or at the last valid visit prior to discontinuation. The time to recurrence was evaluated using Kaplan-Meier methods and compared between the venlafaxine ER and placebo groups using log-rank tests. Secondary outcome measures included rates of response and remission (defined as HAM-D17 ≤ 7). The study was conducted from December 2000 through July 2005. Results: The cumulative probabilities of recurrence through 12 months in the venlafaxine ER (N = 43) and placebo (N = 40) groups were 8.0% (95% CI = 0.0 to 16.8) and 44.8% (95% CI = 27.6 to 62.0), respectively (p < .001). At month 12, using last-observation-carried-forward analysis, the rate of response or remission was significantly higher in the venlafaxine ER group (93%) than in the placebo group (63%; p = .002). Overall discontinuation rates were 28% and 63% in the venlafaxine ER and placebo groups, respectively. Adverse events were the primary reason for discontinuation for 1 patient (2%) in the venlafaxine ER group and 4 (10%) in the placebo group. An analysis of the combined maintenance phases, which compared the risk of recurrence over 24 months for patients assigned to venlafaxine ER (N = 129) or placebo (N = 129) for the first maintenance phase, showed a significantly greater cumulative probability of recurrence through 24 months for the placebo group (47.3% [95% CI = 36.4 to 58.2]) than for the venlafaxine ER group (28.5% [95% CI = 18.3 to 38.7]; p = .005). Conclusion: In this study, an additional 12 months of maintenance therapy with venlafaxine ER was effective in preventing recurrence of depression in patients who had been responders to venlafaxine ER after acute (10 weeks), continuation (6 months), and initial maintenance (12 months) therapy. Trial Registration: ClinicalTrials.gov identifier NCT00046020 (http://www.clinicaltrials.gov).

AB - Objective: To report second-year results from the 2-year maintenance phase of a long-term study to evaluate the efficacy and safety of venlafaxine extended release (ER) in preventing recurrence of depression. Method: Outpatients with recurrent unipolar depression (DSM-IV criteria; N = 1096) were randomly assigned in a 3:1 ratio to 10 weeks of treatment with venlafaxine ER or fluoxetine. Responders (17-item Hamilton Rating Scale for Depression [HAM-D17] total score ≤ 12 and ≥ 50% decrease from baseline) entered a 6-month, double-blind continuation phase on the same medication. Continuation-phase responders were enrolled into maintenance treatment consisting of 2 consecutive 12-month phases. At the start of each maintenance phase, venlafaxine ER responders were randomly assigned to receive double-blind treatment with venlafaxine ER or placebo, and fluoxetine responders were continued for each period. The second 12-month maintenance phase compared the time to recurrence of depression with venlafaxine ER (75 to 300 mg/day) versus placebo as the primary efficacy measure. The primary definition of recurrence was a HAM-D17 total score > 12 and < 50% reduction from baseline (acute phase) at 2 consecutive visits or at the last valid visit prior to discontinuation. The time to recurrence was evaluated using Kaplan-Meier methods and compared between the venlafaxine ER and placebo groups using log-rank tests. Secondary outcome measures included rates of response and remission (defined as HAM-D17 ≤ 7). The study was conducted from December 2000 through July 2005. Results: The cumulative probabilities of recurrence through 12 months in the venlafaxine ER (N = 43) and placebo (N = 40) groups were 8.0% (95% CI = 0.0 to 16.8) and 44.8% (95% CI = 27.6 to 62.0), respectively (p < .001). At month 12, using last-observation-carried-forward analysis, the rate of response or remission was significantly higher in the venlafaxine ER group (93%) than in the placebo group (63%; p = .002). Overall discontinuation rates were 28% and 63% in the venlafaxine ER and placebo groups, respectively. Adverse events were the primary reason for discontinuation for 1 patient (2%) in the venlafaxine ER group and 4 (10%) in the placebo group. An analysis of the combined maintenance phases, which compared the risk of recurrence over 24 months for patients assigned to venlafaxine ER (N = 129) or placebo (N = 129) for the first maintenance phase, showed a significantly greater cumulative probability of recurrence through 24 months for the placebo group (47.3% [95% CI = 36.4 to 58.2]) than for the venlafaxine ER group (28.5% [95% CI = 18.3 to 38.7]; p = .005). Conclusion: In this study, an additional 12 months of maintenance therapy with venlafaxine ER was effective in preventing recurrence of depression in patients who had been responders to venlafaxine ER after acute (10 weeks), continuation (6 months), and initial maintenance (12 months) therapy. Trial Registration: ClinicalTrials.gov identifier NCT00046020 (http://www.clinicaltrials.gov).

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