Evidence map›Paper›PMID 27726982›Full record

SynthesisThe lancet. Psychiatry2016

Placebo response rates in antidepressant trials: a systematic review of published and unpublished double-blind randomised controlled studies.

Toshi A Furukawa, Andrea Cipriani, Lauren Z Atkinson, Stefan Leucht, Yusuke Ogawa, Nozomi Takeshima, Yu Hayasaka, Anna Chaimani, Georgia Salanti

Abstract readSystematic Review
PubMed Publisher
In one paragraph

Synthesis in The lancet. Psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers, 29 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
90citing papers in PubMed, 29 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

90 citing papers in PubMed, 29 syntheses or guidelines pooled it.

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30 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Toshi A FurukawaDepartment of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine/School of Public Health, Kyoto, Japan; Department of Clinical Epidemiology, Kyoto University Graduate School of Medicine/School of Public Health, Kyoto, Japan.
Andrea CiprianiDepartment of Psychiatry, University of Oxford, Oxford, UK. Electronic address: andrea.cipriani@psych.ox.ac.uk.
Lauren Z AtkinsonDepartment of Psychiatry, University of Oxford, Oxford, UK.
Stefan LeuchtDepartment of Psychiatry and Psychotherapy, Technische Universität München, Klinikum rechts der Isar, Munich, Germany.
Yusuke OgawaDepartment of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine/School of Public Health, Kyoto, Japan.
Nozomi TakeshimaDepartment of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine/School of Public Health, Kyoto, Japan.
Yu HayasakaDepartment of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine/School of Public Health, Kyoto, Japan.
Anna ChaimaniInstitute of Social and Preventive Medicine, University of Bern, Bern, Switzerland; Department of Hygiene and Epidemiology, University of Ioannina, Greece.
Georgia SalantiInstitute of Social and Preventive Medicine, University of Bern, Bern, Switzerland; Department of Hygiene and Epidemiology, University of Ioannina, Greece.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPrevious studies have shown that placebo response rates in antidepressant trials have been increasing since the 1970s. However, these studies have been based on outdated or limited datasets and have used inappropriate statistical methods. We did a systematic review of placebo-controlled randomised controlled trials of antidepressants to examine associations between placebo-response rates and study and patient characteristics.

methodsIn this systematic review, we searched for published and unpublished double-blind randomised placebo-controlled trials of first-generation and second-generation antidepressants for acute treatment of major depression in adults (update: Jan 8, 2016). The log-transformed proportions of placebo response, defined as 50% or greater reduction in depression severity score from baseline, were meta-analytically synthesised for each year. We then looked for a structural break point in the secular changes in these characteristics through the years and examined the influence of the study year and other trial and patient characteristics on the response rates through meta-regression.

findingsWe identified 252 placebo-controlled trials (26 324 patients on placebo) done between 1978 and 2015. There was a structural break in 1991, and since then, the average placebo response rates in antidepressant trials have remained constant in the range between 35% and 40% (relative risk [RR] 1·00, 95% CI 0·97-1·03, p=0·99, for every 5-year increase). The length of the study and the number of study centres were significant factors (RR 1·03, 95% CI 1·01-1·05 for 1 more week in trial length; 1·32, 1·11-1·57 for multicentre vs single-centre trials).

interpretationContrary to the widely held belief, the average placebo response rates in antidepressant trials have been stable for more than 25 years. This new evidence should have an effect on the interpretation of the scientific literature and the future of psychopharmacology, both from a clinical and methodological point of view.

fundingJapan Society for Promotion of Science, Great Britain Sasakawa Foundation.

Indexed as

Placebo EffectAntidepressive AgentsAntidepressive Agents, Second-GenerationDouble-Blind MethodHumansMajor Depressive DisorderRandomized Controlled Trials as TopicTreatment OutcomeAntidepressive AgentsAntidepressive Agents, Second-Generation

Identifiers

PMID27726982

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.