ReviewPsychological medicine2022
Clinical research challenges posed by difficult-to-treat depression.
Review in Psychological medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07097025 (Efficacy and Safety of Vagus Nerve Stimulation Treatment in Treatment Resistant Depression), which is not on this map. Cited by 51 papers, 4 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.
Efficacy and Safety of Vagus Nerve Stimulation Treatment in Treatment Resistant Depression
Who cites it
51 citing papers in PubMed, 4 syntheses or guidelines pooled it, 75 citations in OpenAlex.
- Efficacy and Moderators of Mindfulness-Based Cognitive Therapy in Difficult-to-Treat Depression: A Systematic Review and Individual Participant Data Meta-Analysis.Psychotherapy and psychosomatics · 2026Pooled it
- Long-Term Psychodynamic Psychotherapy for Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Depression and anxiety · 2026Pooled it
- Genetics, epigenetics, and neurobiology of childhood-onset depression: an umbrella review.Molecular psychiatry · 2024Pooled it
- Residual insomnia in major depressive disorder: a systematic review.Frontiers in psychiatry · 2023Pooled it
- Mechanisms of mindfulness-based cognitive therapy in difficult-to-treat depression: moderation and mediation analyses from the RESPOND trial.Psychological medicine · 2026Trial
- Durability of the benefit of vagus nerve stimulation in markedly treatment-resistant major depression: a RECOVER trial report.The international journal of neuropsychopharmacology · 2026Trial
- Trial
- Sulforaphane mitigates behavioral deficits in experimental chronic kidney disease through regulation of Nrf2/NLRP3 inflammasome.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- The intersection between race/ethnicity and adverse childhood experiences and its association with depression.Social psychiatry and psychiatric epidemiology · 2026Article
- Interactive dynamic modulation of antidepressant treatment response by serum interleukin-1β and Neuroticism at 12 weeks.Scientific reports · 2026Article
- Review
- Patient and course of care factors impacting time to response and remission in psychotherapy for depression.Frontiers in psychology · 2026Article
- Review
- The relevance of phenotypic definition in treatment resistant forms of major depressive disorder: a narrative review.Frontiers in pharmacology · 2026Review
- Article
- Bridging early life trauma to difficult-to-treat depression: scoping review.BJPsych bulletin · 2025Review
- Beyond symptom improvement: transdiagnostic and disorder-specific ways to assess functional and quality of life outcomes across mental disorders in adults.World psychiatry : official journal of the World Psychiatric Association (WPA) · 2025Article
- Difficult-to-Treat Anxiety: A Neurocomputational Framework.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2025Review
- Multi-omics analysis reveals the mechanism of action of Atractylodin against depression.Journal of natural medicines · 2025Article
- Exploring the Implementation of Gamification as a Treatment Modality for Adults with Depression in Malaysia.Medicina (Kaunas, Lithuania) · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 11 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Approximately one-third of individuals in a major depressive episode will not achieve sustained remission despite multiple, well-delivered treatments. These patients experience prolonged suffering and disproportionately utilize mental and general health care resources. The recently proposed clinical heuristic of 'difficult-to-treat depression' (DTD) aims to broaden our understanding and focus attention on the identification, clinical management, treatment selection, and outcomes of such individuals. Clinical trial methodologies developed to detect short-term therapeutic effects in treatment-responsive populations may not be appropriate in DTD. This report reviews three essential challenges for clinical intervention research in DTD: (1) how to define and subtype this heterogeneous group of patients; (2) how, when, and by what methods to select, acquire, compile, and interpret clinically meaningful outcome metrics; and (3) how to choose among alternative clinical trial design options to promote causal inference and generalizability. The boundaries of DTD are uncertain, and an evidence-based taxonomy and reliable assessment tools are preconditions for clinical research and subtyping. Traditional outcome metrics in treatment-responsive depression may not apply to DTD, as they largely reflect the only short-term symptomatic change and do not incorporate durability of benefit, side effect burden, or sustained impact on quality of life or daily function. The trial methodology will also require modification as trials will likely be of longer duration to examine the sustained impact, raising complex issues regarding control group selection, blinding and its integrity, and concomitant treatments.
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.