Comprehensive Analysis of Remission (COMPARE) with Venlafaxine versus SSRIs

Nemeroff, Charles B.; Entsuah, Richard; Benattia, I.; Demitrack, Mark A.; Sloan, Diane M.; Thase, Michael E.

doi:10.1016/j.biopsych.2007.06.027

Cited by 152 publications

(62 citation statements)

References 63 publications

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“…(Kessler et al, 2003). Unfortunately, current treatments for MDD, produce remission in only about 30% of patients, though response short of remission occurs in about 50–75% (Kennedy et al, 2001; Nemeroff et al 2008; Trivedi et al, 2006). Because there is so much variability in individual outcomes from MDD treatment, there are now increasing efforts to identify factors that may predict the optimal treatment modality for a given patient.…”

Section: Introductionmentioning

confidence: 99%

Depression beliefs, treatment preference, and outcomes in a randomized trial for major depressive disorder

Dunlop

Kelley

Mletzko

et al. 2012

Journal of Psychiatric Research

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Previous studies suggest that individual preferences for medication- or psychotherapy-based treatments for depression may affect outcomes in clinical trials that compare these two forms of treatment. We assessed patients' beliefs about the causes of their depression, their preferred treatment, and strength of that preference in 80 patients participating in a 12-week clinical trial evaluating neuroimaging predictors of response to cognitive behavior therapy (CBT) or escitalopram. Forty-five patients expressed a preference for one of the 2 treatments, but being matched to preference did not influence remission or completion rates. Medication-preferring patients were more likely to terminate the trial early, regardless of treatment received. CBT-preferring patients rarely endorsed unknown causes for their depression, and medication-preferring patients were highly unlikely to identify pessimistic attitudes as a source of their depression. Among patients willing to be randomized to treatment, preference does not appear to strongly influence outcome. Specific preferences for CBT or medication may reflect differing conceptualizations about depressive illness, knowledge of which may enhance treatment retention and efficacy.

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Section: Introductionmentioning

confidence: 99%

Depression beliefs, treatment preference, and outcomes in a randomized trial for major depressive disorder

Dunlop

Kelley

Mletzko

et al. 2012

Journal of Psychiatric Research

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“…However, as has been pointed out elsewhere (Nemeroff et al, 2008), in these studies low doses of paroxetine were often compared to high doses of venlafaxine, and serum paroxetine concentrations were not reported when doses of 30-40 mg/day were used. In effect, therefore, these studies have compared only the SSRI properties of low doses or probably low serum paroxetine concentrations to venlafaxine's dual transporter inhibition at moderate to high doses in some individuals.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, a combination of nortriptyline and fluoxetine or sertraline was more effective than the use of one of these agents alone in ameliorating treatment-resistant depression (Seth et al, 1992). A pooled analysis of all of the Wyethsponsored venlafaxine clinical trials revealed that remission rate differences for venlafaxine vs SSRI therapy were small but statistically significant, largely attributed to venlafaxinefluoxetine differences (Nemeroff et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Estimates of Serotonin and Norepinephrine Transporter Inhibition in Depressed Patients Treated with Paroxetine or Venlafaxine

Owens

Krulewicz

Simon³

et al. 2008

Neuropsychopharmacol

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Paroxetine and venlafaxine are potent serotonin transporter (SERT) antagonists and weaker norepinephrine transporter (NET) antagonists. However, the relative magnitude of effect at each of these sites during treatment is unknown. Using a novel blood assay that estimates CNS transporter occupancy we estimated the relative SERT and NET occupancy of paroxetine and venlafaxine in human subjects to assess the relative magnitude of SERT and NET inhibition. Outpatient subjects (N ¼ 86) meeting criteria for major depression were enrolled in a multicenter, 8 week, randomized, double-blind, parallel group, antidepressant treatment study. Subjects were treated by forced-titration of paroxetine CR (12.5-75 mg/day) or venlafaxine XR (75-375 mg/day) over 8 weeks. Blood samples were collected weekly to estimate transporter inhibition. Both medications produced dose-dependent inhibition of the SERT and NET. Maximal SERT inhibition at week 8 for paroxetine and venlafaxine was 90% (SD 7) and 85% (SD 10), respectively. Maximal NET inhibition for paroxetine and venlafaxine at week 8 was 36% (SD 19) and 60% (SD 13), respectively. The adjusted mean change from baseline (mean 28.6) at week 8 LOCF in MADRS total score was À16.7 (SE 8.59) and À17.3 (SE 8.99) for the paroxetine and venlafaxine-treated patients, respectively. The magnitudes of the antidepressant effects were not significantly different from each other (95%CI À3.42, 4.54, p ¼ 0.784). The results clearly demonstrate that paroxetine and venlafaxine are potent SERT antagonists and less potent NET antagonists in vivo. NET antagonism has been posited to contribute to the antidepressant effects of these compounds. The clinical significance of the magnitude of NET antagonism by both medications remains unclear at present.

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“…An NNT of 3 would mean that for every three patients who are treated with combination antidepressants as compared to those patients who are receiving fluoxetine monotherapy, one additional patient experiences remission of depression. This is a low number that indicates considerable efficacy; to compare, the advantage of venlafaxine over selective serotonin reuptake inhibitor (SSRI) monotherapy has been reported as an NNT of 17, with the 95% confidence interval running from 12 to 26 (Nemeroff et al, 2008).…”

Section: Statistical Critiquementioning

confidence: 97%

Reanalyzing a Randomized Controlled Trial of Combination Antidepressant Treatment With Mirtazapine: Confidence Intervals Suggest Substantial Uncertainty

Lacasse

2011

Ethical Hum Psychol Psychiatry

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This article subjects a randomized controlled trial (RCT) published in the American Journal of Psychiatry to a methodological and statistical critique, including a reanalysis of the effect size statistics presented. The published trial tested the use of combination antidepressants (mirtazapine coprescribed with either bupropion, venlafaxine, or fluoxetine) at treatment initiation as compared with fluoxetine monotherapy. The authors report that combination therapy was effective, with a number-needed-to-treat (NNT) statistic of 3-5, a strong effect size. Scrutiny of the methodology and clinical trial registration shows that 4 of 6 preregistered outcomes were statistically nonsignificant, 1 outcome was not reported, and 1 unregistered outcome was published. The well-critiqued Hamilton Depression Inventory was the only positive outcome measure. Calculating confidence intervals for the reported NNT demonstrates substantial uncertainty (95% CI for NNT 5 2.3-18.0). In an era of evidence-based psychiatric practice, there is insufficient evidence to recommend combination therapy at initiation of treatment.

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Comprehensive Analysis of Remission (COMPARE) with Venlafaxine versus SSRIs

Cited by 152 publications

References 63 publications

Depression beliefs, treatment preference, and outcomes in a randomized trial for major depressive disorder

Depression beliefs, treatment preference, and outcomes in a randomized trial for major depressive disorder

Estimates of Serotonin and Norepinephrine Transporter Inhibition in Depressed Patients Treated with Paroxetine or Venlafaxine

Reanalyzing a Randomized Controlled Trial of Combination Antidepressant Treatment With Mirtazapine: Confidence Intervals Suggest Substantial Uncertainty

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