Trial reportBMJ (Clinical research ed.)2022
Response to acute monotherapy for major depressive disorder in randomized, placebo controlled trials submitted to the US Food and Drug Administration: individual participant data analysis.
Trial report in BMJ (Clinical research ed.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 7 of them syntheses that pooled 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.
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.
Who cites it
53 citing papers in PubMed, 7 syntheses or guidelines pooled it, 105 citations in OpenAlex.
- Cognitive and affective effects of L-Theanine: a systematic review and meta-analysis of 31 randomized trials.Molecular psychiatry · 2026Pooled it
- Efficacy of Pharmacological Interventions in Milder Depression: A Systematic Review and Meta-Analysis.Neuropsychopharmacology reports · 2025Pooled it
- Comparing apples and oranges in youth depression treatments? A quantitative critique of the evidence base and guidelines.BMJ mental health · 2025Pooled it
- Placebo effects in randomized trials of pharmacological and neurostimulation interventions for mental disorders: An umbrella review.Molecular psychiatry · 2024Pooled it
- Hype or hope? High placebo response in major depression treatment with ketamine and esketamine: a systematic review and meta-analysis.Frontiers in psychiatry · 2024Pooled it
- Placebo response in trials with patients with anxiety, obsessive-compulsive and stress disorders across the lifespan: a three-level meta-analysis.BMJ mental health · 2023Pooled it
- Effectiveness of yoga for major depressive disorder: A systematic review and meta-analysis.Frontiers in psychiatry · 2023Pooled it
- Trajectory of response to esketamine nasal spray for treatment resistant depression: Findings from ESCAPE-TRD.European psychiatry : the journal of the Association of European Psychiatrists · 2026Trial
- High Dose Vitamin B6 Reduces Depression Symptoms.Depression and anxiety · 2026Trial
- Safety and Efficacy of the NMDA-2b-Selective Negative Allosteric Modulator BI 1569912: A Phase Ib Randomized Trial in Major Depressive Disorder.Clinical pharmacology and therapeutics · 2025Trial
- Investigating the Relationship Between Cannabis Expectancies and Anxiety, Depression, and Pain Responses After Acute Flower and Edible Cannabis Use.Cannabis and cannabinoid research · 2025Trial
- Long-Term Effects of Internet-Based Cognitive Behavioral Therapy on Depression Prevention Among University Students: Randomized Controlled Factorial Trial.JMIR mental health · 2024Trial
- Individualized fMRI connectivity defines signatures of antidepressant and placebo responses in major depression.Molecular psychiatry · 2023Trial
- NMDA subunit 2B-selective negative allosteric modulator satoprodil (BI 1569912) as mono- and adjunctive therapy in patients with major depressive disorder: results from two phase 2 randomized, controlled trials.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Permissive and instructive causality: integrating biological and environmental factors in mental health.Psychological medicine · 2026Review
- Article
- Novel approaches in depression treatment: from rapid-acting antidepressants to personalized interventions.Molecular psychiatry · 2026Review
- Article
- Blocking the Reflection: Milestones and Hurdles for Digital Twins in Mental Health.Pharmacopsychiatry · 2026Review
- Measuring and appraising placebo effects in clinical trials: contemporary challenges and approaches in psychiatry.The lancet. Psychiatry · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesTo characterize individual participant level response distributions to acute monotherapy for major depressive disorder in randomized, placebo controlled trials submitted to the US Food and Drug Administration from 1979 to 2016.
designIndividual participant data analysis. POPULATION: 232 randomized, double blind, placebo controlled trials of drug monotherapy for major depressive disorder submitted by drug developers to the FDA between 1979 and 2016, comprising 73 388 adult and child participants meeting the inclusion criteria for efficacy studies on antidepressants.
main outcome measuresResponses were converted to Hamilton Rating Scale for Depression (HAMD17) equivalent scores where other measures were used to assess efficacy. Multivariable analyses examined the effects of age, sex, baseline severity, and year of the study on improvements in depressive symptoms in the antidepressant and placebo groups. Response distributions were analyzed with finite mixture models.
resultsThe random effects mean difference between drug and placebo favored drug (1.75 points, 95% confidence interval 1.63 to 1.86). Differences between drug and placebo increased significantly (P<0.001) with greater baseline severity. After controlling for participant characteristics at baseline, no trends in treatment effect or placebo response over time were found. The best fitting model of response distributions was three normal distributions, with mean improvements from baseline to end of treatment of 16.0, 8.9, and 1.7 points. These distributions were designated Large, Non-specific, and Minimal responses, respectively. Participants who were treated with a drug were more likely to have a Large response (24.5%
conclusionsThe trimodal response distributions suggests that about 15% of participants have a substantial antidepressant effect beyond a placebo effect in clinical trials, highlighting the need for predictors of meaningful responses specific to drug treatment.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.