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Depression (major depressive disorder) — master index¶
Last curated: 2026-10-29 · status: draft sweep updates awaiting independent audit · 18 wiki pages · 26 open questions
Scope note. This condition covers major depressive disorder (MDD)—unipolar depression. Depressive episodes within bipolar disorder are therapeutically distinct and live in ../bipolar-disorder/.
The condition in five sentences. MDD is a heterogeneous clinical syndrome: US lifetime DSM-5 prevalence is 20.6%, yet 3,703 STAR*D patients expressed 1,030 symptom profiles (Hasin 2018, PMID 29450462; Fried 2015, PMID 25451401). Global burden is dominated by disability and a major treatment gap, while conventional accounting underrepresents mortality pathways (GBD 2019, PMID 35026139; Thornicroft 2017, PMID 27908899). Antidepressants, structured psychotherapies, and their combination work on average, but effects are modest, heterogeneous, and historically distorted by selective publication (Cipriani 2018, PMID 29477251; Cuijpers 2020, PMID 31922679; Turner 2008, PMID 18199864). Repeated failure worsens prognosis and forces choices among augmentation, ECT, TMS, ketamine/esketamine, and investigational psychedelics without a definitive head-to-head sequence (Rush 2006, PMID 17074942; Anand 2023, PMID 37224232). Mechanistically, no universal serotonin deficiency or validated biomarker explains MDD; polygenic, stress, immune, metabolic, plasticity, and circuit processes likely combine differently across people (Moncrieff 2023, PMID 35854107; Howard 2019, PMID 30718901; Kennis 2020, PMID 31745238).
Reading paths¶
- Fast orientation: overview → diagnosis and heterogeneity → epidemiology and burden.
- Treatment evidence: antidepressant pharmacology → efficacy debate → psychotherapy and combination → TRD.
- Rapid and device treatments: ketamine → neuromodulation → psychedelics → trials.
- Mechanism and precision: neurobiology → genetics → biomarkers.
- Safety and systems: suicide and mortality → red flags → guidelines → patient experience.
Pages¶
This table is the canonical page list.
| File | Scope | Status |
|---|---|---|
| overview.md | definition, burden, treatment and mechanism map | curated |
| diagnostic-criteria-and-heterogeneity.md | DSM/ICD anchors, symptom heterogeneity, specifiers, bipolar boundary | curated |
| epidemiology-and-burden.md | prevalence, DALYs, economic cost, treatment gap | curated |
| neurobiology-and-mechanisms.md | monoamines, HPA, plasticity, inflammation, circuits | draft |
| genetics.md | heritability, GWAS, polygenicity, gene–environment interplay | curated |
| antidepressant-pharmacology.md | classes, efficacy, adverse effects, withdrawal | curated |
| the-efficacy-debate.md | severity, publication bias, STAR*D, clinical significance | curated |
| psychotherapy-and-combination.md | CBT/IPT/behavioral activation, combination and sequencing | curated |
| treatment-resistant-depression.md | definitions, pseudo-resistance, augmentation, escalation | curated |
| ketamine-and-glutamatergic-agents.md | ketamine, esketamine, dextromethorphan, durability and safety | draft |
| neuromodulation.md | ECT, TMS/iTBS, tDCS, VNS, DBS | draft |
| psychedelics-and-novel-therapeutics.md | psilocybin, blinding, neurosteroids and pipeline | draft |
| biomarkers-and-treatment-prediction.md | blood, imaging, genetic, digital prediction and validation | draft |
| suicide-risk-and-mortality.md | suicidal outcomes, prediction limits, excess mortality | curated |
| guidelines.md | CANMAT, VA/DoD, ACP, NICE and disagreements | draft |
| clinical-trials-landscape.md | live registry snapshot, pipeline, trial failure modes | draft |
| patient-experience-and-advocacy.md | identity, function, treatment burden, organizations | curated |
| red-flags-and-safety-concerns.md | urgency, diagnostic reassessment, treatment hazards | curated |
Literature layer¶
| Artifact | Contents | Status |
|---|---|---|
| BIBLIOGRAPHY.md | legacy bibliography plus the 15, 22 and 29 October sweep selections | draft |
| notes/ | 5 landmark notes: STAR*D, Cipriani, Turner, ketamine, SNT | built |
| guidelines/REGISTRY.md | current, specialty, and legacy records; 29 October surveillance checkpoint | draft |
| statistics/STATISTICS.md | source-qualified estimates; WHO fact sheet rechecked 29 October 2026, figures unchanged; US MDD healthcare-spending estimate added | draft |
| patient-voice/ | ethics/method, organizations, themes, and public campaign sources through 22 October | draft |
| OPEN-QUESTIONS.md | 26 stable tiered questions; OQ-9 now covers intranasal mebufotenin and OQ-16 a negative multimodal relapse-prediction study | draft |
Curation state¶
Independent audit completed 2026-08-30. At that audit, all 18 pages met the 150–400-line and 25–60-verified-citation targets and were curated; 388/388 condition PMIDs and 27/27 NCT identifiers resolved through live official APIs in the final corpus state. The audit corrected a wrong citation, a numeric overstatement, six study-design labels, two stale absence claims, one stale organization record, one unresolved guideline item, and 85 bibliography reverse mappings. Those findings describe the August audit, not independent verification of later additions. Trial status and organization availability remain dated, time-sensitive snapshots.
The 2026-10-15 sweep updated four wiki pages, the bibliography, guideline surveillance, statistics, public patient sources and research questions. The 2026-10-22 sweep added a negative home tDCS trial, a postmortem hippocampal-neurogenesis study, and the recruiting CoMPACT protocol; it refreshed all 28 previously cited trial records without an overall-status change. The 2026-10-29 sweep added a phase 2b trial of single-dose intranasal mebufotenin in TRD, a multimodal relapse-prediction study in which clinical features alone did best, a late-life neuromodulation network meta-analysis, and a US healthcare-spending estimate. It refreshed the 30 previously cited trial records; none changed overall status. Edited pages are draft pending the separate audit. Full-text limits, the unreachable Cochrane Library and SciELO, and the unchanged WHO figures are recorded in the log.