ReviewInternational clinical psychopharmacology2018
The conundrum of depression clinical trials: one size does not fit all.
Review in International clinical psychopharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis 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
14 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Raising Placebo Efficacy in Antidepressant Trials Across Decades Explained by Small-Study Effects: A Meta-Reanalysis.Frontiers in psychiatry · 2020Pooled it
- Extended-release ketamine tablets for treatment-resistant depression: a randomized placebo-controlled phase 2 trial.Nature medicine · 2024Trial
- Placebo response mitigation with a participant-focused psychoeducational procedure: a randomized, single-blind, all placebo study in major depressive and psychotic disorders.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Trial
- Are People Worse Off in a Mental Health Treatment Paradigm Where Medication Is Deemphasised? A Naturalistic Noninferiority Trial of an Initiative to Improve Patient Choice.The International journal of social psychiatry · 2026Article
- Exploring the neural mechanisms of electroacupuncture for cognitive impairment in depression using functional near-infrared spectroscopy: a randomized controlled trial.Frontiers in psychiatry · 2025Article
- A measure of reliability convergence to select and optimize cognitive tasks for individual differences research.Communications psychology · 2024Article
- Digital and precision clinical trials: innovations for testing mental health medications, devices, and psychosocial treatments.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Review
- "The Heart Asks Pleasure First"-Conceptualizing Psychiatric Diseases asBrain sciences · 2022Article
- Precision clinical trials: a framework for getting to precision medicine for neurobehavioural disorders.Journal of psychiatry & neuroscience : JPN · 2021Review
- Poor Separation of Clinical Symptom Profiles by DSM-5 Disorder Criteria.Frontiers in psychiatry · 2021Article
- Shortcomings of Trials Assessing Antidepressants in the Management of Irritable Bowel Syndrome: A Critical Review.Journal of clinical medicine · 2020Review
- Article
- Power behind the throne: A clinical trial simulation study evaluating the impact of controllable design factors on the power of antidepressant trials.International journal of methods in psychiatric research · 2019Article
- Significance of Participants' Expectations in Managing the Placebo Effect in Antidepressant Research.Frontiers in psychiatry · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In this paper we review the history of antidepressant (AD) development, since the discovery of imipramine in 1957 to the present day. Through this exploration we will show that the increasing placebo response is likely a red herring and that a higher magnitude of placebo response is not an adequate explanation for AD trials' high failure rates. As a better explanation for their lack of success, we will examine some of the fundamental flaws of AD clinical trials and their origins in historical forces. We focus on underpowering, which occurs as a consequence of unrealistic expectations for AD performance. In addition, we describe the lack of precision in the depression outcome measurements for the past 40 years and show how these measures contrast with those used in clinical trials of other chronic diseases, which use simpler outcome measures. Finally, we describe the role of regulatory agencies in influencing clinical trial design and how the assumption that 'one size fits all' for the past 60 years has led to flawed design of AD clinical trials.
Indexed as
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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.