Efficacy and Safety of Desvenlafaxine 50 mg/d for Prevention of Relapse in Major Depressive Disorder: A Randomized Controlled Trial
Abstract
OBJECTIVE: To evaluate the long-term (11-month) efficacy and safety of desvenlafaxine (administered as desvenlafaxine succinate) at the recommended 50-mg/d dose in preventing relapse in patients with major depressive disorder (MDD). METHOD: Adult outpatients (age ≥ 18 years) with MDD (DSM-IV criteria) and a 17-item Hamilton Depression Rating Scale (HDRS17) total score ≥ 20 at screening and baseline were enrolled in a multicenter, double-blind, placebo-controlled, randomized withdrawal trial conducted between June 2009 and March 2011. Patients who responded to 8-week open-label treatment with desvenlafaxine 50 mg/d with continuing stable response through week 20 were randomly assigned to receive placebo or desvenlafaxine 50 mg/d in a 6-month, double-blind, randomized withdrawal period. The primary efficacy endpoint was time to relapse following randomization to double-blind treatment, which was compared between groups using the log-rank test. Relapse was defined as HDRS17 total score ≥ 16, discontinuation for unsatisfactory response, hospitalization for depression, suicide attempt, or suicide. Safety and tolerability data were collected throughout the trial. RESULTS: A total of 874 patients were enrolled; 548 patients were randomly assigned to receive placebo (n = 276) or desvenlafaxine 50 mg/d (n = 272) in the double-blind withdrawal period. Time to relapse was significantly shorter for placebo versus desvenlafaxine (P < .001). At the end of the 6-month double-blind treatment, the estimated probability of relapse was 30.2% for placebo versus 14.3% for desvenlafaxine 50 mg/d. Safety and tolerability results were generally consistent with those in short-term studies of desvenlafaxine 50 mg/d. CONCLUSIONS: Desvenlafaxine at the recommended dose of 50 mg/d was effective in relapse prevention of depression during a 6-month period in patients who demonstrated stable response after 20 weeks of open-label desvenlafaxine treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00887224.
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20 articles define relapse with psychometric measures (Hamilton Depression Rating Scale, Beck Depression Inventory, Montgomery-Asberg Depression Rating Scale, Goldberg Anxiety and Depression Scale, Clinical Global Impression).
“20 do so with psychometric measures (Hamilton Depression Rating Scale, Beck Depression Inventory, Montgomery-Asberg Depression Rating Scale, Goldberg Anxiety and Depression Scale, Clinical Global Impression) (4, 7, 9, 13–18, 33, 34, 42–49)”
From Administrative criteria in the relapse of depressive disorder: a critical appraisal (2026) · cites this paper as [18]
Suicide/suicide attempt is mentioned 19 times as an administrative criterion.
“Suicide/suicide attempt is mentioned 19 times (1, 15, 16, 18, 19, 26, 27, 33, 37, 38, 41, 43–46, 48–50, 52)”
From Administrative criteria in the relapse of depressive disorder: a critical appraisal (2026) · cites this paper as [18]
The median time to a new episode with antidepressant treatment continued has averaged approximately 40 months, compared to just over 1 year if treatment was discontinued.
“The median time to a new episode with antidepressant treatment continued has averaged approximately 40 months, compared to just over 1 year if treatment was discontinued (Baldessarini, 2013; Rosenthal et al., 2013).”
From Prevention of Relapse and Recurrence in Adults with Major Depressive Disorder: Systematic Review and Meta-Analyses of Controlled Trials (2016) · cites this paper as Rosenthal et al., 2013
The relapse rates observed in the current study were similar to those reported in recently completed studies with desvenlafaxine versus placebo (13.6% vs. 28.3%) and vortioxetine versus placebo (13% vs. 26%).
“the relapse rates observed in the current study were similar to those reported in recently completed studies with desvenlafaxine versus placebo (13.6% vs. 28.3%; Rosenthal, Boyer, Vialet, Hwang, & Tourian, 2013) and vortioxetine versus placebo (13% vs. 26%; Boulenger, Loft, & Florea, 2012).”
From Relapse prevention with levomilnacipran ER in adults with major depressive disorder: a multicenter, randomized, double-blind, placebo-controlled study (2019) · cites this paper as Rosenthal, Boyer, Vialet, Hwang, & Tourian, 2013
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“, 2013a, 2015), and prevention of relapse of depressive symptoms has also been reported with desvenlafaxine 50 mg/day and desvenlafaxine 200–400 mg/day compared with placebo (Rickels et al., 2010; Rosenthal et al., 2013).”
BackgroundDesvenlafaxine for the treatment of major depressive disorder
Kornstein, S. G., McIntyre, R. S., Thase, M. E., & Boucher, M. (2014) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2014.923403 · Cited by 20 · see citing works
“Continuation efficacy and safety, and increased time to relapse versus placebo has been demonstrated at the 50 mg/d dose [76-79,81].”
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“There is a dearth in randomized-controlled trials (RCT) analyzing the long-term efficacy of prophylactic treatment as trials of this sort seldom extend beyond 12 months of maintenance treatment (Gilaberte et al., 2001; Gelenberg et al., 2003; Montgomery et al., 2004; Detke et al., 2004; Rosenthal et al., 2013).”
BackgroundBaldessarini, R. J., Lau, W. K., Sim, J. Z. T., Sum, M. Y., & Sim, K. (2016) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyw092 · Cited by 19 · see citing works
“…of all subjects and treatments (Kornstein et al., 2006; Parahia et al., 2006; Keller et al., 2007; Kelin et al., 2010; Liebowitz et al., 2010; Rosenthal et al., 2013), rates of early loss averaged 56.6% (554/979) with antidepressants vs 64.3% (653/1016) with placebos (χ2 = 12.3, P = .0004).”
BackgroundInfluentialSafety and Tolerability of Desvenlafaxine in Children and Adolescents with Major Depressive Disorder
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“The most common TEAEs reported by children and adolescents in this study were similar to those listed in short-term and long-term desvenlafaxine trials in adult patients with MDD (Clayton et al. 2009; Tourian et al. 2011; Rosenthal et al. 2013).”
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“Results from individual clinical trials and pooled analyses have demonstrated the effectiveness of desvenlafaxine 50 mg/day for reducing the symptoms of MDD (Boyer et al., 2008; Clayton et al., 2013, 2014; Dunlop et al., 2011; Iwata et al., 2013; Liebowitz et al., 2008; Rosenthal et al., 2013; Soares et al., 2009; Tou…”
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“In several of these studies, the authors acknowledged the problem by conducting sensitivity analyses of their efficacy measure, excluding data from the first few weeks after randomization (Allgulander, Florea, & Huusom, 2006; Kornstein et al., 2006; Rosenthal et al., 2013).”
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“…been assessed for the treatment of MDD in short-term and longer-term clinical trials (DeMartinis et al., 2007; Boyer et al., 2008; Liebowitz et al., 2008; Tourian et al., 2009; Dunlop et al., 2011; Clayton et al., 2013a, 2015; Iwata et al., 2013; Liebowitz et al., 2013; Rosenthal et al., 2013).”
MethodSelf-citationMosca, D., Zhang, M., Prieto, R., & Boucher, M. (2017) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000000674 · Cited by 9 · see citing works
“Previous short- and long-term studies have evaluated the antidepressant efficacy of desvenlafaxine, as well as prevention of relapse of depressive symptoms, compared with placebo.(35,36) The short-term efficacy of desvenlafaxine has also been demonstrated in patient subgroups, with significant improvement in depressiv…”
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“By contrast, long-term safety regarding BP change was documented in a double-blind, placebo-controlled, randomized withdrawal study with 50 mg/d of desvenlafaxine, where there was no significant BP change at the final evaluation when compared to the placebo [25].”
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“…from the withheld post-randomization phase of the six positive trials (Boulenger 2012), (Durgam 2019), (Goodwin 2013 Study 2), (Rickels 2010), (Rosenthal 2013), and (Thase 2022) but a greater reduction than the negative and/or weak-effects trials of (Durgam 2018), (Goodwin 2013 Study 1), and…”
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- Authors
- Rosenthal, J. Z., Boyer, P., Vialet, C., Hwang, E., & Tourian, K. A.
- Corresponding author
- Rosenthal, Joshua Z.
- ORCID
- Boyer, Patrice
- Venue
- The Journal of Clinical Psychiatry
- Publisher
- Physicians Postgraduate Press, Inc
- Published
- 2013-02-15
- Volume
- 74
- Issue
- 02
- Pages
- 158-166
- ISSN
- 0160-6689 (ISSN-L)
- OpenAlex
- W1967591091
- Cited by
- 37
- References
- 0
- Citations by year
- 2026: 2 · 2025: 3 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 4 · 2019: 1 · 2018: 2 · 2017: 3 · 2016: 5 · 2015: 6 · 2014: 5 · 2013: 1
- FWCI
- 4.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Social Sciences › Psychology › Social Psychology › Mental Health Treatment and Access
- Keywords
- desvenlafaxine, major depressive disorder, relapse prevention, antidepressant maintenance, serotonin-norepinephrine reuptake inhibitors, long-term efficacy, drug safety and tolerability, withdrawal trial, treatment-resistant depression
- MeSH terms
- Desvenlafaxine Succinate, Antidepressive Agents, Cyclohexanols, Major Depressive Disorder, Double-Blind Method, Female, Humans, Male, Middle Aged, Treatment Outcome, Selective Serotonin Reuptake Inhibitors, Kaplan-Meier Estimate, Secondary Prevention
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