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Generalized anxiety disorder — master index

Last curated: 2026-09-02 · status: built, awaiting independent audit · 19 of 19 pages written · 387 verified papers · 40 open questions · 18 "dots not yet connected"

The condition in five sentences. Generalized anxiety disorder is defined by persistent, excessive and difficult-to-control worry with associated arousal symptoms lasting at least six months (DeMartini 2019, PMID 30934083), and it is the anxiety disorder whose diagnostic boundary is least settled: the WHO World Mental Health surveys put DSM-5 lifetime prevalence at 3.7% across 26 countries (Ruscio 2017, PMID 28297020), while the same group has published the case for deleting the excessiveness criterion — a change that would raise global lifetime prevalence from 2.6% to 4.0% (Ruscio 2024, PMID 39364896) — and taxometric analyses find no categorical boundary at all (Marcus 2014, PMID 24377439). Treatment works and works modestly: antidepressants beat placebo with high-certainty evidence and NNTB 7 for response (Kopcalic 2025, PMID 39880377), CBT beats treatment as usual at SMD −0.74 (Papola 2024, PMID 37851421), and continuation treatment cuts relapse from 56% to 19% (Allgulander 2006, PMID 16316482). The condition carries measurable excess mortality — all-cause RR 1.48, natural-cause RR 1.55 (Wagner 2026, PMID 42136520) — and its treatments are perceived as helpful by 70% of those who receive them, yet only 34.6% ever obtain treatment and just 29.7% would persist through enough encounters to reach that point (Stein 2021, PMID 34372811). The recurring hazard for anyone reading this literature is pooling: most apparent GAD evidence is anxiety-disorder evidence or GAD-with-depression evidence, and GAD has the second-highest placebo response of any psychiatric disorder (d_av 1.23; Bschor 2024, PMID 38809560), so real effects look small and pooled effects look like GAD effects when they are not.

Start here: wiki/overview.md. Research frontier: OPEN-QUESTIONS.md. Growth history: LOG.md. Every source: literature/BIBLIOGRAPHY.md.

At a glance

Layer State
Wiki pages 19 of 19 independently audited, all status: curated
Total lines of wiki prose ~2,830
Verified papers cited 399 distinct PMIDs, every one retrieved live from PubMed E-utilities on 2026-09-02
Trial registry records 38 distinct NCT records retrieved live from the ClinicalTrials.gov v2 API on 2026-09-02; one non-GAD record was explicitly excluded
Non-journal sources 27 URLs checked live on 2026-09-02: 20 returned HTTP 200, 6 returned bot/Cloudflare 403, and 1 failed to connect; failures remain labelled
Landmark notes 6
Guideline registry 26 documents, with superseded-by chains, a disagreements section and a watch list
Statistics sheet ~13 topic tables plus 13 stated conflicts and caveats
Patient-voice layer 4 files: method/ethics, 24 organisations (1 recorded as closed, 6 unverifiable), 7 themes, annotated sources with 8 coverage limits
Open questions 40 with stable IDs, tiered 1–3, plus an 18-row "dots not yet connected" table

The three borders that define this condition

  1. This condition owns GAD, not anxiety. Panic disorder, social anxiety disorder, specific phobias, agoraphobia and separation anxiety are not curated here; OCD is excluded and is no longer classified as an anxiety disorder in DSM-5. Pooled sources are used where they must be and are labelled pooled at every point of use — a pooled anxiety-disorder effect size is not a GAD effect size.
  2. Comorbid depression is cross-linked, not absorbed. The GAD–MDD genetic correlation approaches unity in women (Kendler 2007, PMID 17121688), yet pure GAD is common in primary care and impairs as much as pure MDD (Wittchen 2002, PMID 12044105; Hoffman 2008, PMID 17146763). Depression is curated separately.
  3. PTSD is a neighbour, not a subset. Seeded alongside this condition; each cross-links the other rather than restating it.

Pages

The canonical page list for this condition (CONVENTIONS §5). Link only to these filenames.

# Section Page Scope Lines Cites Status
1 Foundations overview.md What GAD is, the three borders, map of the condition, the numbers worth memorising 129 27 curated
2 Foundations diagnosis-and-classification.md DSM-5 and ICD-11 criteria, where each element came from, instruments, the reliability record since 1983 149 33 curated
3 Controversy the-diagnostic-boundary.md Excessiveness, uncontrollability, duration, symptom count; taxometrics; separability from depression; network bridges; HiTOP and RDoC; the pooling hazard 152 38 curated
4 Foundations epidemiology-and-burden.md Prevalence 0.4–7.4% by criteria and instrument, age/sex, GBD burden, the treatment gap 142 33 curated
5 Mechanism mechanism-and-models.md Five worry models, intolerance of uncertainty, neuroimaging, HRV, cognition, ERP, inflammation, genetics 139 39 curated
6 Assessment screening-and-measurement.md GAD-7/GAD-2 accuracy, population-specific thresholds, PHQ-4, HAM-A, USPSTF policy, measurement-based care 152 33 curated
7 Treatment cognitive-behavioural-therapy.md Effect sizes by comparator, applied relaxation, protocol and format, low-intensity CBT, mechanisms of change 150 27 curated
8 Treatment other-psychological-therapies.md Metacognitive therapy, MBSR vs escitalopram, ACT, psychodynamic, ERT, MI augmentation, exercise, acupuncture, phytoceuticals 149 37 curated
9 Treatment ssri-and-snri-pharmacotherapy.md Cochrane NNTB 7, drug ranking, dose and time course, trial-level detail, relapse prevention, discontinuation 170 30 curated
10 Treatment pregabalin-benzodiazepines-and-others.md Pregabalin, benzodiazepines, quetiapine, buspirone, agomelatine, silexan, cannabinoids; remission-based ranking 171 35 curated
11 Treatment digital-and-remote-delivery.md iCBT and app trials, the format contradiction, guidance and adherence, conversational agents 125 29 curated
12 Treatment treatment-resistant-gad.md Consensus definition, historical heterogeneity, augmentation evidence, sequencing, neurostimulation, novel mechanisms 149 33 curated
13 Course course-relapse-and-long-term-outcome.md Clinic vs community prognosis, predictors, relapse prevention, mortality, cognition, cardiovascular outcomes 145 25 curated
14 Population special-populations.md Children and adolescents incl. CAMS/CAMELS, older adults, perinatal, students, veterans 143 39 curated
15 Clinical comorbidity-and-primary-care.md Recognition failure, comorbidity structure, somatic presentation, collaborative care, substance use, perceived helpfulness 161 38 curated
16 Reference guidelines.md Agreement, four live disagreements, stepped care, population-specific guidance, and whether concordance helps 144 43 curated
17 Frontier clinical-trials-landscape.md The placebo problem, landmark and pipeline trials with live NCT records, trial-population representativeness, endpoint choice 163 30 curated
18 Human red-flags-and-safety-concerns.md Suicidality, medical mimics, medication harms with numbers, dependence and misuse, a practical red-flag list 154 38 curated
19 Human patient-experience-and-advocacy.md Seven lived-experience themes, treatment preference as a measurable force, perceived helpfulness, the advocacy landscape 148 31 curated

Literature layer

File Contents
literature/BIBLIOGRAPHY.md All 399 verified papers, grouped by the section they principally serve, with tags and cited-by lists
literature/notes/ 6 landmark notes: Spitzer 2006 — the GAD-7; Ruscio 2017 — cross-national epidemiology; Ruscio 2024 — eliminating excessiveness; Slee 2019 — the drug network; Kendler 1992 — same genes; Bschor 2024 — placebo across nine disorders
literature/guidelines/REGISTRY.md 26 documents worldwide with superseded-by chains, seven live disagreements, five structural gaps and a seven-item watch list
literature/statistics/STATISTICS.md Quick-reference tables — prevalence by measurement frame, burden, mortality, comorbidity, treatment gap, effect sizes, course, measurement performance, trial methodology, safety — plus 13 stated conflicts
literature/patient-voice/ README (method + ethics), organizations.md (24 organisations, verification status recorded), themes.md (7 themes, each ≥2 sources), sources.md (annotated, with coverage limits)

Reading paths

Anchor records — re-verified at build

All nine seed anchors were re-fetched live from PubMed on 2026-09-02 and every one resolved with matching author, year and journal. None was discarded.

PMID Year First author Journal Where it is now used
16717171 2006 Spitzer RL Arch Intern Med The GAD-7 — landmark note, screening and measurement
40130828 2025 Aktürk Z Cochrane Database Syst Rev GAD-7/GAD-2 accuracy — screening and measurement
28297020 2017 Ruscio AM JAMA Psychiatry Cross-national epidemiology — landmark note, epidemiology and burden
39364896 2024 Ruscio AM Psychol Med Eliminating excessiveness — landmark note, the diagnostic boundary
30712879 2019 Slee A Lancet Drug network meta-analysis — landmark note, SSRI and SNRI pharmacotherapy
31494377 2019 Chen TR J Psychiatr Res Drug + psychotherapy network (allows all comorbidities) — SSRI and SNRI pharmacotherapy
29451967 2018 Carpenter JK Depress Anxiety CBT vs placebo (pooled anxiety disorders; GAD in the large-effect stratum) — cognitive behavioural therapy
27687212 2016 Hall J Am J Geriatr Psychiatry CBT for late-life GAD — special populations
20633738 2010 Kroenke K Gen Hosp Psychiatry PHQ somatic/anxiety/depressive scales — screening and measurement

Curation state

Layer State
Wiki pages 19 of 19 independently audited; all curated
Literature layer Complete: bibliography, 6 notes, guideline registry, statistics, patient-voice
Open questions Rewritten: 40 tiered questions, 18-row dots table
Independent audit Completed 2026-09-02 by Codex; original author Claude. See LOG.md.

Audit complete. All cited identifiers were re-fetched live, stale absence claims were rerun and corrected, and page-level citation coverage was rechecked. Future sweeps should repeat the dated absence searches and registry-status checks.