Development and validation of a prediction model for the probability of responding to placebo in antidepressant trials: a pooled analysis of individual patient data

Shinohara, Kiyomi; Tanaka, Shiro; Noma, Hisashi; Maruo, Kazushi; Cipriani, Andrea; Yamawaki, Shigeto; Furukawa, Toshi A

doi:10.1136/ebmental-2018-300073

Cited by 8 publications

(6 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It should also be noted that a high placebo response may impact the estimated efficacy of antidepressants ( 38 ). Indeed, a higher placebo response in children and adolescents, compared to adults, with MDD has been reported, alongside a less strong placebo response to the same antidepressants in children and adolescents with Ads ( 11 ).…”

Section: Discussionmentioning

confidence: 99%

Antidepressants in Children and Adolescents: Meta-Review of Efficacy, Tolerability and Suicidality in Acute Treatment

et al. 2020

Self Cite

View full text Add to dashboard Cite

Antidepressants are prescribed for the treatment of a number of psychiatric disorders in children and adolescents, however there is still controversy about whether they should be used in this population. This meta-review aimed to assess the effects of antidepressants for the acute treatment of attention-deficit/hyperactivity disorder (ADHD), anxiety disorders (ADs), autistic spectrum disorder (ASD), enuresis, major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and posttraumatic stress disorder (PTSD) in children and adolescents. Efficacy was measured as response to treatment (either as mean overall change in symptoms or as a dichotomous outcome) and tolerability was measured as the proportion of patients discontinuing treatment due to adverse events. Suicidality was measured as suicidal ideation, behavior (including suicide attempts) and completed suicide. PubMed, EMBASE, and Web of Science were systematically searched (until 31 October 2019) for existing systematic reviews and/or meta-analyses of double-blind randomized controlled trials. The quality of the included reviews was appraised using AMSTAR-2. Our meta-review included nine systematic reviews/meta-analyses (2 on ADHD; 1 on AD; 2 on ASD; 1 on enuresis; 1 on MDD, 1 on OCD and 1 on PTSD). In terms of efficacy this review found that, compared to placebo: fluoxetine was more efficacious in the treatment of MDD, fluvoxamine and paroxetine were better in the treatment of AD; fluoxetine and sertraline were more efficacious in the treatment of OCD; bupropion and desipramine improved clinician and teacher-rated ADHD symptoms; clomipramine and tianeptine were superior on some of the core symptoms of ASD; and no antidepressant was more efficacious for PTSD and enuresis. With regard to tolerability: imipramine, venlafaxine, and duloxetine were less well tolerated in MDD; no differences were found for any of the antidepressants in the treatment of anxiety disorders (ADs), ADHD, and PTSD; tianeptine and citalopram, but not clomipramine, were less well tolerated in children and adolescents with ASD. For suicidal behavior/ideation, venlafaxine (in MDD) and paroxetine (in AD) were associated with a significantly increased risk; by contrast, sertraline (in AD) was associated with a reduced risk. The majority of included systematic reviews/meta-analyses were rated as being of high or moderate in quality by the AMSTAR-2 critical appraisal tool (one and five, respectively). One included study was of low quality and two were of critically low quality. Compared to placebo, selected antidepressants can be efficacious in the acute treatment of some common psychiatric disorders, although statistically significant differences do not always translate into clinically significant results. Little information was available about tolerability of antidepressants in RCTs of OCD and in the treatment of ADHD, ASD, MDD, and PTSD. There is a paucity of data on suicidal ideation/behavior, but paroxetine may increase the risk of suicidality in the treatment of AD and ven...

show abstract

Section: Discussionmentioning

confidence: 99%

Antidepressants in Children and Adolescents: Meta-Review of Efficacy, Tolerability and Suicidality in Acute Treatment

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…We have assured transitivity in our network with regard to these variables by limiting our samples to participants with non-psychotic unipolar major depression. Other clinical or methodological variables that may influence our primary outcomes of antidepressant efficacy or acceptability include age,14 depressive severity at baseline15 and the dosing schedule 16. We will investigate if these variables are similarly distributed across studies grouped by comparison.…”

Section: Methods and Analysismentioning

confidence: 99%

Side effect profile and comparative tolerability of 21 antidepressants in the acute treatment of major depression in adults: protocol for a network meta-analysis

Tomlinson

Efthimiou

Boaden

et al. 2019

Evid Based Mental Health

Self Cite

View full text Add to dashboard Cite

IntroductionWe have recently compared all second-generation as well as selected first-generation antidepressants in terms of efficacy and acceptability in the acute treatment of major depression. Here we present a protocol for a network meta-analysis aimed at extending these results, updating the evidence base and comparing all second-generation as well as selected first-generation antidepressants in terms of specific adverse events and tolerability in the acute treatment of major depression in adults.Methods and analysisWe will include all double-blind randomised controlled trials comparing one active drug with another or with placebo in the acute treatment major depression in adults. We will compare the following active agents: agomelatine, amitriptyline, bupropion, citalopram, clomipramine, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, levomilnacipran, milnacipran, mirtazapine, nefazodone, paroxetine, reboxetine, sertraline, trazodone, venlafaxine, vilazodone and vortioxetine. The main outcomes will include the total number of patients experiencing specific adverse events; experiencing serious adverse events; and experiencing at least one adverse event. Published and unpublished studies will be retrieved through relevant database searches, trial registries and websites; reference selection and data extraction will be completed by at least two independent reviewers. For each outcome we will undertake a network meta-analysis to synthesise all evidence. We will use local and global methods to evaluate consistency. We will perform all analyses in R. We will assess the quality of evidence contributing to network estimates with the Confidence in Network Meta-Analysis web application.DiscussionThis work will provide an in- depth analysis and an insight into the specific adverse events of individual antidepressants.Ethics and disseminationThis review does not require ethical approval.PROSPERO registration numberCRD42019128141.

show abstract

“…Investigating symptom trajectories over time could enable researchers to cluster study participants into different types of responders (73). Gueorguieva and colleagues (74), for example, have investigated trajectories of depression severity in clinical trials of duloxetine showing that placebo-treated patients were characterized by different trajectories than responders and nonresponders in the antidepressant-treated subsample.…”

Section: Advantages Of Using Mobile Apps For Placebo Researchmentioning

confidence: 99%

Optimizing Expectations via Mobile Apps: A New Approach for Examining and Enhancing Placebo Effects

2019

View full text Add to dashboard Cite

There is growing interest in interventions that enhance placebo responses in clinical practice, given the possibility that this would lead to better patient health and more effective therapy outcomes. Previous studies suggest that placebo effects can be maximized by optimizing patients’ outcome expectations. However, expectancy interventions are difficult to validate because of methodological challenges, such as reliable blinding of the clinician providing the intervention. Here we propose a novel approach using mobile apps that can provide highly standardized expectancy interventions in a blinded manner, while at the same time assessing data in everyday life using experience sampling methodology (e.g., symptom severity, expectations) and data from smartphone sensors. Methodological advantages include: 1) full standardization; 2) reliable blinding and randomization; 3) disentangling expectation effects from other factors associated with face-to-face interventions; 4) assessing short-term (days), long-term (months), and cumulative effects of expectancy interventions; and 5) investigating possible mechanisms of change. Randomization and expectancy interventions can be realized by the app (e.g., after the clinic/lab visit). As a result, studies can be blinded without the possibility for the clinician to influence study outcomes. Possible app-based expectancy interventions include, for example, verbal suggestions and imagery exercises, although a large number of possible interventions (e.g., hypnosis) could be evaluated using this innovative approach.

show abstract

Development and validation of a prediction model for the probability of responding to placebo in antidepressant trials: a pooled analysis of individual patient data

Cited by 8 publications

References 31 publications

Antidepressants in Children and Adolescents: Meta-Review of Efficacy, Tolerability and Suicidality in Acute Treatment

Antidepressants in Children and Adolescents: Meta-Review of Efficacy, Tolerability and Suicidality in Acute Treatment

Side effect profile and comparative tolerability of 21 antidepressants in the acute treatment of major depression in adults: protocol for a network meta-analysis

Optimizing Expectations via Mobile Apps: A New Approach for Examining and Enhancing Placebo Effects

Contact Info

Product

Resources

About