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Patient Expectancy as a Mediator of Placebo Effects in Antidepressant Clinical Trials

Published on Feb 1, 2017in American Journal of Psychiatry13.655
· DOI :10.1176/appi.ajp.2016.16020225
Bret R. Rutherford20
Estimated H-index: 20
,
Melanie M. Wall67
Estimated H-index: 67
+ 6 AuthorsSteven P. Roose52
Estimated H-index: 52
Sources
Abstract
Objective:Causes of placebo effects in antidepressant trials have been inferred from observational studies and meta-analyses, but their mechanisms have not been directly established. The goal of this study was to examine in a prospective, randomized controlled trial whether patient expectancy mediates placebo effects in antidepressant studies.Method:Adult outpatients with major depressive disorder were randomly assigned to open or placebo-controlled citalopram treatment. Following measurement of pre- and postrandomization expectancy, participants were treated with citalopram or placebo for 8 weeks. Independent samples t tests determined whether patient expectancy differed between the open and placebo-controlled groups, and mixed-effects models assessed group effects on Hamilton Depression Rating Scale (HAM-D) scores over time while controlling for treatment assignment. Finally, mediation analyses tested whether between-group differences in patient expectancy mediated the group effect on HAM-D scores.Resul...
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  • Citations (38)
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References13
Newest
Placebo response in clinical trials of antidepressant medications is substantial and has been increasing. High placebo response rates hamper efforts to detect signals of efficacy for new antidepressant medications, contributing to trial failures and delaying the delivery of new treatments to market. Media reports seize upon increasing placebo response and modest advantages for active drugs as reasons to question the value of antidepressant medication, which may further stigmatize treatments for ...
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#1Bret R. Rutherford (Columbia University)H-Index: 20
#2Sue M. MarcusH-Index: 29
Last. Steven P. Roose (Columbia University)H-Index: 52
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Background This study is a randomized, prospective, investigation of the relationships between clinical trial design, patient expectancy, and the outcome of treatment with antidepressant medication.
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#1Arif Khan (Duke University)H-Index: 27
#2Amritha BhatH-Index: 7
Last. Walter A. Brown (Brown University)H-Index: 36
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The increasing rate of failure of antidepressant clinical trials has led to the assertion that antidepressants do not have meaningful clinical benefits. Our hypothesis was that the decrease in antidepressant-placebo differences in antidepressant clinical trials over the past three decades could be explained by changes in research design features rather than a lack of potency of the antidepressants being tested. We collected data from 130 double blind placebo controlled antidepressant clinical tr...
47 CitationsSource
Objective: To determine if the inclusion of a placebo arm and/or the number of active comparators in antidepressant trials influences the response rates of the active medication and/or placebo. Data Sources: Searches of MEDLINE, PsycINFO, and pharmaceutical Web sites for published trials or trials conducted but unpublished between January 1996 and October 2007. Study Selection: 2,275 citations were reviewed, 285 studies were retrieved, and 90 were included in the analysis. Trials reporting respo...
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#2Madhukar H. TrivediH-Index: 91
Last. Maurizio FavaH-Index: 106
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Objective: This report describes the participants and compares the acute and longer-term treatment outcomes associated with each of four successive steps in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. Method: A broadly representative adult outpatient sample with nonpsychotic major depressive disorder received one (N=3,671) to four (N=123) successive acute treatment steps. Those not achieving remission with or unable to tolerate a treatment step were encouraged to m...
2,119 CitationsSource
Objective: To evaluate the association between treatment expectations and response in a 9-week, single-blind experimental antidepressant treatment study. Method: Twenty-five adult subjects meeting DSM-IV criteria for major depressive disorder with Hamilton Rating Scale for Depression (HAM-D) scores of ≥ 17 completed a treatment trial using the experimental antidepressant reboxetine. Following a 1-week placebo lead-in, subjects received single-blind treatment for 8 weeks with reboxetine 8 to 10 m...
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Abstract Background: Although residual symptoms after remission from depression are common and predict early relapse, little is known about the impact of residual symptoms on longer-term clinical course of depression or social functioning. Methods: Sixty severe recurrent depressives, who remitted from an index episode of depression with residual symptoms or below residual symptomatology, were followed-up at 8–10 years. Subjects underwent detailed longitudinal interviewing on course of depression...
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#1Björn Meyer (LSU: Louisiana State University)H-Index: 33
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Prior analyses from the National Institute of Mental Health Treatment of Depression Collaborative Research Program indicated that patients' expectancies of treatment effectiveness (S. M. Sotsky et al., 1991) and the quality of the therapeutic alliance (J. L. Krupnick et al., 1996) predicted clinical improvement. These data were reanalyzed to examine the hypothesis that the link between treatment expectancies and outcome would be mediated by patients' contribution to the alliance. Among 151 patie...
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Background This study investigated the relationship of clinical, neuropsychological, and electrophysiological measures of prefrontal dysfunction with treatment response in elderly patients with major depression. Methods Forty-nine depressed elderly subjects were studied before and after 6 weeks of adequate antidepressant treatment and compared with 22 psychiatrically normal controls. The psychomotor retardation item of the Hamilton Depression Rating Scale, the initiation/perseveration subscore o...
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Mean effect sizes for changes in depression were calculated for 2,318 patients who had been randomly assigned to either antidepressant medication or placebo in 19 double-blind clinical trials. As a proportion of the drug response, the placebo response was constant across different types of medication (75%), and the correlation between placebo effect and drug effect was .90. These data indicate that virtually all of the variation in drug effect size was due to the placebo characteristics of the s...
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OBJECTIVES: Age-related hearing loss (ARHL) is a prevalent condition associated with increased risk for depression and cognitive decline. This 12-week prospective, double-blind pilot randomized controlled trial (RCT) of hearing aids (HAs) for depressed older adults with ARHL evaluated the feasibility of a novel research design. METHODS/DESIGN: N=13 individuals aged >/=60 years with Major Depressive Disorder or Persistent Depressive Disorder and at least mild hearing loss (pure tone average >/=30...
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OBJECTIVE: As a post-approval commitment, this dose-ranging study was undertaken to evaluate efficacy and safety of onabotulinumtoxinA in adolescents. BACKGROUND: In adolescents, migraine is often undiagnosed or misdiagnosed and can present unique management challenges. OnabotulinumtoxinA was approved for prevention of chronic migraine (CM) in adults in 2010. METHODS: This multicenter, double-blind, parallel-group, randomized trial assessed a single treatment of onabotulinumtoxinA (155 U or 74 U...
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Abstract Background Adverse events (AEs) are known to occur while patients are treated with placebos, part of the so-called nocebo effect. Yet evidence is limited regarding the likelihood that specific AEs occurring with antidepressant treatment are or are not due to nocebo effects. Methods This study identified 56 placebo-controlled, randomized controlled trials (RCTs) of antidepressant monotherapy for adults with major depressive disorder that reported AE rates in sufficient detail for compari...
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Introduction: Tactile stimulation during a placebo treatment could enhance its credibility and thereby boost positive treatment expectations and the placebo effect. This experimental study aimed to investigate the interplay between tactile stimulation, expectation, and treatment credibility for the placebo effect in nausea. Methods: 90 healthy participants were exposed to a 20-min vection stimulus on two separate days and were randomly allocated to one of three groups on the second day after the...
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The antidepressant placebo response remains a barrier to the development of novel therapies for depression, despite decades of efforts to identify and methodologically address its clinical correlates. This manuscript reviews recent neuroimaging studies that aim to identify the neural signature of antidepressant placebo response. Data captured in clinical trials have primarily focused on antidepressant efficacy or predicting antidepressant response and have reliably implicated the rostral anterio...
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#1Sigal Zilcha-ManoH-Index: 17
#2Patrick J. BrownH-Index: 15
Last. Bret R. RutherfordH-Index: 20
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#1Sigal Zilcha-Mano (University of Haifa)H-Index: 17
#2Zhishun WangH-Index: 27
Last. Bret R. RutherfordH-Index: 20
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Abstract Background Patient expectancy of therapeutic improvement is a primary mediator of placebo effects in antidepressant clinical trials, but its mechanisms are poorly understood. This study employed a novel antidepressant trial design, with integrated functional magnetic resonance imaging (fMRI), to manipulate patient outcome expectancy and examine its neural mediators. Method Twenty-three depressed outpatients, in a randomized controlled trial were assigned to either Open (high outcome exp...
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A symposium held at the 31st European College of Neuropsychopharmacology congress in October 2018 in Barcelona, Spain discussed patients’ expectations of treatment of their depression and how these can be integrated into patient management. Since treatment non-compliance is a major problem in patients suffering from depression, it is important to identify patients’ expectations to improve treatment compliance and in turn efficacy. Currently, there is no established protocol for choosing the righ...
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