An Integrated Analysis of the Efficacy of Desvenlafaxine Compared with Placebo in Patients with Major Depressive Disorder

Thase, Michael E.; Kornstein, Susan G.; Germain, Jean-Michel; Jiang, Qin; Guico-Pabia, Christine J.; Ninan, Philip T.

doi:10.1017/s1092852900020125

Cited by 55 publications

(42 citation statements)

References 27 publications

(12 reference statements)

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“…[73] In a recent meta-analysis of the new antidepressant desvenlafaxine that included 1342 patients, the response NNT was eight (53% response rate for desvenlafaxine vs 41% for placebo) and the remission NNT was 11 (32% remission with desvenlafaxine vs 23% remission with placebo). [74] Furthermore, in another recent meta-analysis with pooled data from the entire class of second-generation antidepressants compared with placebo, the NNT for preventing both relapse and recurrence was five. [75] Finally, from our pooled analysis, we calculated that the response and remission NNTs of aripiprazole were seven (95% CI 5, 11) and eight (95% CI 6, 13), respectively, which were statistically significant (table I).…”

Section: Clinical Implications Of Efficacy Findingsmentioning

confidence: 99%

Aripiprazole as Adjunctive Therapy for Patients with Major Depressive Disorder

2011

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Aripiprazole was initially approved to treat schizophrenia and later approved for bipolar mania, as a monotherapy and an adjunctive therapy (manic or mixed episodes), and for irritability associated with autism. Aripiprazole is a partial agonist at dopamine D(2) and D(3) and serotonin 5-HT(1A) receptors, and is an antagonist at 5-HT(2A) receptors. This profile, and convincing preliminary data from small-scale studies, provided the rationale for the large-scale exploration of aripiprazole for unipolar depression. Recently, three 6-week, large-scale, randomized, double-blind, placebo-controlled clinical trials demonstrated clinically meaningful efficacy for aripiprazole as an adjunctive therapy to antidepressants for treating major depressive disorder (MDD). In November 2007, aripiprazole was approved by the US FDA as an adjunctive therapy to antidepressants for treating MDD, with support from two of the above-mentioned trials. In the trials, aripiprazole was demonstrated to be safe and well tolerated, and showed a minimal trend for weight gain over the course of a 6-week treatment. The incidence of akathisia was higher than that reported in studies of patients with schizophrenia; however, most cases were mild to moderate and infrequently lead to discontinuation (5/1090 from all three trials). This comprehensive review provides an overview of the data from all three 6-week studies (including a pooled analysis) and from an unpublished 52-week, open-label extension study, to inform physicians and facilitate reasonable treatment decisions. In addition, specific issues associated with the use of aripiprazole as an adjunctive therapy in patients with MDD, including possible early treatment effect, appropriate timing of therapy initiation, appropriate dosing and duration of treatment, possible differential effect on depressive subgroups and long-term tolerability, are also discussed.

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Section: Clinical Implications Of Efficacy Findingsmentioning

confidence: 99%

Aripiprazole as Adjunctive Therapy for Patients with Major Depressive Disorder

2011

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“…The efficacy and tolerability of desvenlafaxine at doses ranging from 10 mg/day to 400 mg/day have been assessed in adults with MDD. In integrated analyses of pooled data from adult, fixed-dose studies of desvenlafaxine for MDD, rates of adverse events (AEs) and discontinuations caused by AEs increased with increasing desvenlafaxine dose, and no additional efficacy benefit was observed at doses above the lowest effective dose of 50 mg/day (Clayton et al 2009;Thase et al 2009). …”

Section: Introductionmentioning

confidence: 99%

Safety and Tolerability of Desvenlafaxine in Children and Adolescents with Major Depressive Disorder

Findling

Groark

Chiles

et al. 2014

Journal of Child and Adolescent Psychopharmacology

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Objective: The purpose of this study was to assess long-term safety and tolerability of desvenlafaxine (administered as desvenlafaxine succinate) in children and adolescents with major depressive disorder (MDD). Methods: An 8 week, multicenter, open-label, fixed-dose study of children (ages 7-11 years) and adolescents (ages 12-17 years) with MDD was followed by a 6 month, flexible-dose extension study. Patients were administered desvenlafaxine 10-100 mg/day (children) or 25-200 mg/day (adolescents) for a total of 8 months. Treatment-emergent adverse events (AEs), withdrawals because of AEs, laboratory tests, vital signs, and the Columbia Suicide-Severity Rating Scale (C-SSRS) were collected. Eight month safety results from the lead-in plus extension studies are reported for extension study participants, using lead-in study day -1 as baseline. Results: Forty patients were enrolled in both studies (20 children; 20 adolescents). Of those, four children and three adolescents withdrew because of AEs. Treatment-emergent AEs reported by three or more patients were upper abdominal pain (15%) and headache (15%) in children, and somnolence (30%), nausea (20%), upper abdominal pain (15%), and headache (15%) in adolescents. Negativism (oppositional behavior) in a child was the single serious AE reported. No deaths occurred during the lead-in or extension studies. Mean pulse rates demonstrated statistically significant increases from lead-in study baseline to final evaluation (children, + 5.2 bpm; adolescents, + 5.9 bpm; p £ 0.05). No statistically significant change in blood pressure was observed at final evaluation. Two adolescents (0 children) reported suicidal ideation on the C-SSRS at screening assessment and during the lead-in and/or extension trials; one adolescent reported suicidal ideation after screening only. Conclusions: Long-term (8 month) treatment with desvenlafaxine was generally safe and well tolerated in depressed children and adolescents.

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“…Treatment guidelines suggest that individual patients with partial response to antidepressant treatment may respond more fully to higher doses 1,41,42 . Although no dose optimization studies have been conducted for desvenlafaxine, previously published integrated analyses of efficacy and safety have indicated that in clinical trial settings, desvenlafaxine doses of 50 to 400 mg/d provided similar efficacy (based on group mean changes in HAM-D 17 total scores and remission rates) 43 , but tolerability decreased with higher doses 44 .…”

Section: Discussionmentioning

confidence: 99%