Depression (major depressive disorder) — master index¶
Last curated: 2026-08-30 · status: audited · 18 wiki pages · 385 unique wiki PMIDs · 25 open questions · 12 literature-layer files
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 | curated |
| 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 | curated |
| neuromodulation.md | ECT, TMS/iTBS, tDCS, VNS, DBS | curated |
| psychedelics-and-novel-therapeutics.md | psilocybin, blinding, neurosteroids and pipeline | curated |
| biomarkers-and-treatment-prediction.md | blood, imaging, genetic, digital prediction and validation | curated |
| suicide-risk-and-mortality.md | suicidal outcomes, prediction limits, excess mortality | curated |
| guidelines.md | CANMAT, VA/DoD, ACP, NICE and disagreements | curated |
| clinical-trials-landscape.md | live registry snapshot, pipeline, trial failure modes | curated |
| 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 | all 388 condition PMIDs, including 385 unique wiki PMIDs, topic-grouped with exact cited-by mappings | audited |
| notes/ | 5 landmark notes: STAR*D, Cipriani, Turner, ketamine, SNT | built |
| guidelines/REGISTRY.md | 18 current, specialty, and legacy guideline records; disagreements and watch list | built |
| statistics/STATISTICS.md | 60+ source-qualified prevalence, diagnostic, mechanism, treatment, harm, and burden estimates | built |
| patient-voice/ | ethics/method, verified organizations, themes, annotated sources | built |
| OPEN-QUESTIONS.md | 25 stable tiered questions plus 16 junction hypotheses | built |
Curation state¶
Independent audit completed 2026-08-30. All 18 pages meet the 150–400-line and 25–60-verified-citation targets and are 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. No substantive verification flag remains. Trial status and organization availability remain dated, time-sensitive snapshots.