Antidepressant treatment history and drug-placebo separation in a placebo-controlled trial in major depressive disorder

Hunter, Aimee M.; Cook, Ian A.; Tartter, Molly; Sharma, Simi K.; Disse, Gregory D.; Leuchter, Andrew F.

doi:10.1007/s00213-015-4047-2

Cited by 12 publications

(13 citation statements)

References 29 publications

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“…Depressive symptoms were generally responsive to treatment with the DA agonist pramipexole, suggesting DA system mediation of treatment response. Inference of a specific dopaminergic mechanism of response, however, is limited by absence of a placebo treatment group and likelihood of nonspecific influences in an antidepressant-naive sample (85). …”

Section: Discussionmentioning

confidence: 99%

Dopamine Release in Antidepressant-Naive Major Depressive Disorder: A Multimodal [11C]-(+)-PHNO Positron Emission Tomography and Functional Magnetic Resonance Imaging Study

Schneier

Slifstein

Whitton

et al. 2018

Biological Psychiatry

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[C]-(+)-PHNO demonstrated high sensitivity to displacement by amphetamine-induced dopamine release, but dopamine release capacity and D/D availability were not associated with ventral striatal activation to reward prediction error or clinical features, in this study powered to detect large effects. While a preponderance of indirect evidence implicates dopaminergic dysfunction in MDD, these findings suggest that presynaptic dopamine dysregulation may not be a feature of MDD or a prerequisite for treatment response to dopamine agonists.

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Section: Discussionmentioning

confidence: 99%

Dopamine Release in Antidepressant-Naive Major Depressive Disorder: A Multimodal [11C]-(+)-PHNO Positron Emission Tomography and Functional Magnetic Resonance Imaging Study

Schneier

Slifstein

Whitton

et al. 2018

Biological Psychiatry

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“…Thus, the variation in effect size may be attributed to the difference in response to placebo, rather than difference in response to augmentation. Indeed, a recent study has shown lower placebo response rates in patients who have failed more prior active treatments(4). There may be biological differences in those who are nonresponsive to 2 or more antidepressants where a multi-receptor approach is required and achieved by combination of 2 different drugs classes.…”

Section: Discussionmentioning

confidence: 99%

Impact of Prior Treatment on Remission of Late-Life Depression with Venlafaxine and Subsequent Aripiprazole or Placebo Augmentation

Hsu

Mulsant

Lenze³

et al. 2016

The American Journal of Geriatric Psychiatry

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Objectives Prior treatment history can inform clinical decisions about subsequent treatment choices. We examined the impact of prior antidepressant treatment on outcome of treatment with venlafaxine only and then with augmentation with aripiprazole or placebo in depressed older adults. Methods We analyzed outcome data from a randomized, placebo-controlled clinical trial of aripiprazole augmentation in depressed older adults. The study consisted of an open-label lead-in phase with venlafaxine XR, followed by a placebo-controlled phase of aripiprazole augmentation. Prior treatment history was assessed with the Antidepressant Treatment History Form. Results Documented prior treatment failure predicted a reduced remission rate with venlafaxine. However, aripiprazole augmentation was efficacious in those with prior treatment failure (42.6% remission with aripiprazole vs 25.8% with placebo; χ2 = 3.87 df = 1, p = 0.049). Conclusions Aripiprazole augmentation is an efficacious strategy in older depressed adults who fail to remit with two or more adequate antidepressant trials, including a course of venlafaxine.

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“…Two studies conducted by Aimee Hunter and colleagues at UCLA provide indirect support for this hypothesis (53, 54). In each of these studies, depressed patients in clinical trials were grouped according to whether they had ever been on antidepressants before.…”

Section: Is There a Drug Effect At All?mentioning

confidence: 99%

Placebo Effect in the Treatment of Depression and Anxiety

Kirsch

2019

Front. Psychiatry

144

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The aim of this review is to evaluate the placebo effect in the treatment of anxiety and depression. Antidepressants are supposed to work by fixing a chemical imbalance, specifically, a lack of serotonin or norepinephrine in the brain. However, analyses of the published and the unpublished clinical trial data are consistent in showing that most (if not all) of the benefits of antidepressants in the treatment of depression and anxiety are due to the placebo response, and the difference in improvement between drug and placebo is not clinically meaningful and may be due to breaking blind by both patients and clinicians. Although this conclusion has been the subject of intense controversy, the current article indicates that the data from all of the published meta-analyses report the same results. This is also true of recent meta-analysis of all of the antidepressant data submitted to the Food and Drug Administration (FDA) in the process of seeking drug approval. Also, contrary to previously published results, the new FDA analysis reveals that the placebo response has not increased over time. Other treatments (e.g., psychotherapy and physical exercise) produce the same benefits as antidepressants and do so without the side effects and health risks of the active drugs. Psychotherapy and placebo treatments also show a lower relapse rate than that reported for antidepressant medication.

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Antidepressant treatment history and drug-placebo separation in a placebo-controlled trial in major depressive disorder

Abstract: Treatment history appears to constitute a factor that is distinct from other commonly studied illness characteristics or expectancy measures, and that impacts overall response as well as drug-placebo separation in RCTs.

Cited by 12 publications

References 29 publications

Dopamine Release in Antidepressant-Naive Major Depressive Disorder: A Multimodal [11C]-(+)-PHNO Positron Emission Tomography and Functional Magnetic Resonance Imaging Study

Dopamine Release in Antidepressant-Naive Major Depressive Disorder: A Multimodal [11C]-(+)-PHNO Positron Emission Tomography and Functional Magnetic Resonance Imaging Study

Impact of Prior Treatment on Remission of Late-Life Depression with Venlafaxine and Subsequent Aripiprazole or Placebo Augmentation

Placebo Effect in the Treatment of Depression and Anxiety

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