P.1.189 Venlafaxine and SSRIs: Pooled remission analysis

Nemeroff, Charles B.; Entsuah, A.R.; Willard, Lauren; Demitrack, Mark A.; Thase, M.E.

doi:10.1016/s0924-977x(03)91899-2

Cited by 4 publications

(6 citation statements)

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“…While not significant, the remission rate for the SSRI arm in this trial was higher than the placebo arm (39% and 30%, respectively). These rates are marginally higher, but in agreement with, a pooled analysis of double-blind, randomized sertraline trials totaling over 4000 patients with MDD (35% and 24% for sertraline and placebo, respectively) [44]. We report evidence of early-treatment CT and volume alterations that differentially associate with clinical treatment response across placebo and sertraline treatment groups.…”

Section: Discussionsupporting

confidence: 85%

“…Therefore, if pretreatment and early-treatment structural data were presently translated to the clinic as a biomarker for treatment response, 97.6% of patients would be expected to not remit. Clearly, a treatment biomarker that classifies 2% of patients as remitters, when SSRI remission rates are typically in the range of 30-40% [44], is not at a stage to be of immediate clinical use. The fact that the expected, and experimentally determined, nonremission rate for sertraline is approximately 60-70% makes the threshold for accepting a treatment response predictor much higher than if response rates were higher.…”

Section: Discussionmentioning

confidence: 99%

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Pretreatment and early-treatment cortical thickness is associated with SSRI treatment response in major depressive disorder

Bartlett

DeLorenzo

Sharma

et al. 2018

Neuropsychopharmacol

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To date, there are no biomarkers for major depressive disorder (MDD) treatment response in clinical use. Such biomarkers could allow for individualized treatment selection, reducing time spent on ineffective treatments and the burden of MDD. In search of such a biomarker, multisite pretreatment and early-treatment (1 week into treatment) structural magnetic resonance (MR) images were acquired from 184 patients with MDD randomized to an 8-week trial of the selective serotonin reuptake inhibitor (SSRI) sertraline or placebo. This study represents a large, multisite, placebo-controlled effort to examine the association between pretreatment differences or early-treatment changes in cortical thickness and treatment-specific outcomes. For standardization, a novel, robust site harmonization procedure was applied to structural measures in a priori regions (rostral and caudal anterior cingulate, lateral orbitofrontal, rostral middle frontal, and hippocampus), chosen based on previously published reports. Pretreatment cortical thickness or volume did not significantly associate with SSRI response. Thickening of the rostral anterior cingulate cortex in the first week of treatment was associated with better 8-week responses to SSRI (p = 0.010). These findings indicate that frontal lobe structural alterations in the first week of treatment may be associated with long-term treatment efficacy. While these associational findings may help to elucidate the specific neural targets of SSRIs, the predictive accuracy of pretreatment or early-treatment structural alterations in classifying treatment remitters from nonremitters was limited to 63.9%. Therefore, in this large sample of adults with MDD, structural MR imaging measures were not found to be clinically translatable biomarkers of treatment response to SSRI or placebo.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Pretreatment and early-treatment cortical thickness is associated with SSRI treatment response in major depressive disorder

Bartlett

DeLorenzo

Sharma

et al. 2018

Neuropsychopharmacol

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“…For example, in clinical example 1, the 8 venlafaxine studies for the pooled analysis were selected because they were used for registration with the US Food and Drug Administration (28). A subsequent pooled analysis, the Comprehensive Pooled Analysis of Remission Data (COMPARE), included the full dataset of 33 published and unpublished Wyeth-sponsored studies of venlafaxine (29) and confirmed the earlier analysis results.…”

Section: Clinical Examplementioning

confidence: 99%

Using Metaanalysis to Evaluate Evidence: Practical Tips and Traps

Lam

Kennedy

2005

Can J Psychiatry

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Although practising evidence-based medicine is the goal of most physicians, it can be a real challenge to sift through the vast body of data to determine the best strategies. Most clinical guidelines regard replicated randomized controlled trials (RCTs), metaanalyses, and systematic reviews as the highest level of evidence to support treatment recommendations. High-quality metaanalyses can overcome many of the drawbacks of individual RCTs and qualitative reviews. They can reduce bias, provide adequate power to demonstrate real differences in outcomes, and resolve the results of inconsistent studies. This paper focuses on basic principles and terms used in metaanalysis, so that clinicians can appropriately evaluate and use their results to guide treatment decisions.

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“…7,15 Despite the broadly similar efficacy of different antidepressants in preventing relapse, there is growing evidence that they are not all equally effective in terms of speed of response and degree of remission. [16][17][18][19][20][21][22][23] The long-feared absolute mechanistic barrier to a fast action seems to have been a red herring, although the most widely prescribed group, the SSRIs, do have a built-in limitation because of their negative feedback action upon 5-HT autoreceptors. 11,24 Of the current antidepressants, the evidence for faster action and more remission is strongest for the two dual action agents, venlafaxine [21][22][23] and mirtazapine [16][17][18][19][20] , although there is emerging data on a third such drug, duloxetine.…”

Section: Recoverymentioning

confidence: 99%

“…[16][17][18][19][20][21][22][23] The long-feared absolute mechanistic barrier to a fast action seems to have been a red herring, although the most widely prescribed group, the SSRIs, do have a built-in limitation because of their negative feedback action upon 5-HT autoreceptors. 11,24 Of the current antidepressants, the evidence for faster action and more remission is strongest for the two dual action agents, venlafaxine [21][22][23] and mirtazapine [16][17][18][19][20] , although there is emerging data on a third such drug, duloxetine. 25 Such inferences can only be drawn when a consistent advantage is demonstrated across multiple methodologies, of which the most rigorous and sensitive appears to be survival analysis.…”

Section: Recoverymentioning

confidence: 99%

Depression may be associated with hippocampal volume changes and HPA axis dysfunction: is treatment to remission the answer?: review article

Pinder¹

2004

Afr. J. Psych

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Under-treatment of depression is common practice and carries substantial risks of relapse and recurrence while increasing morbidity and mortality in co-morbid medical illnesses. It may also lead to or exacerbate structural brain changes in depression, most particularly in the hippocampus, with an accompanying decline in cognitive functioning. Treatment to full remission of symptoms and maintaining patients in remission is therefore essential. Although all current antidepressants seem to provide comparable efficacy in preventing relapse, some of the newer dual action antidepressants can induce a faster response and produce greater degrees of remission. However, remission rates are low even with the best treatments. There remains a need for treatments that will act quickly to reverse not only the symptoms of depression but also the accompanying brain abnormalities.

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P.1.189 Venlafaxine and SSRIs: Pooled remission analysis

Cited by 4 publications

References 0 publications

Pretreatment and early-treatment cortical thickness is associated with SSRI treatment response in major depressive disorder

Pretreatment and early-treatment cortical thickness is associated with SSRI treatment response in major depressive disorder

Using Metaanalysis to Evaluate Evidence: Practical Tips and Traps

Depression may be associated with hippocampal volume changes and HPA axis dysfunction: is treatment to remission the answer?: review article

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