Bipolar disorder — master index¶
Last curated: 2026-10-23 · status: sweeps applied, awaiting independent audit (11 pages remain draft)
Build at a glance: 18 wiki pages (7 curated, 11 draft) · 440 distinct PubMed records condition-wide plus one DOI-cited preprint · 40 NCT identifiers named in the condition, of which 37 are tracked in the trial portfolio and 3 are named only as screened and not added (NCT06229210, NCT06696755, NCT07789340), plus 3 ISRCTN records on the trials page · 6 audited landmark notes · 34 guideline/consensus entries · 166 statistics rows · 13 verified public organizations · 25 tiered open questions and 14 cross-domain junctions. All 393 PMIDs and 33 NCT IDs were live-resolved during the 2026-09-03 independent audit. Records added on 2026-10-09, 2026-10-16 and 2026-10-23 were live-resolved in those sweeps and await independent audit. The previous “38 NCT” headline counted 35 records cited outside the log together with the 3 screened identifiers. This sweep adds NCT07890805 and NCT07664852 to the portfolio, which brings the portfolio to 37 and the named set to 40.
The condition in five sentences. Bipolar disorder is a recurrent mood disorder defined by mania or hypomania, usually with a longitudinal burden dominated by depression and subsyndromal symptoms rather than continuous euthymia (Nierenberg 2023, PMID 37815563; Joffe 2004, PMID 14996142). World Mental Health surveys estimated lifetime prevalence of 0.6% for bipolar I, 0.4% for bipolar II and 1.4% for subthreshold bipolar disorder, while three-quarters of spectrum cases had another mental disorder (Merikangas 2011, PMID 21383262). It is highly polygenic: a 2021 analysis of 41,917 cases identified 64 loci (Mullins 2021, PMID 34002096), and a 2025 multi-ancestry meta-analysis of 158,036 cases and 2,796,499 controls reported 298 loci whose architecture differs by how cases were ascertained and by bipolar subtype, while ancestry transfer of polygenic scores remains weak (O'Connell 2025, PMID 39843750; Li 2021, PMID 33263727). Treatment is phase-specific—antipsychotics, lithium and valproate anchor acute mania; several antipsychotics and combinations have modest short-term bipolar-depression effects; lithium, lamotrigine, valproate and antipsychotics differ in polarity-specific maintenance benefit and harm (Kishi 2022, PMID 34642461; Yildiz 2023, PMID 37595997; Miura 2014, PMID 26360999). The unresolved priorities are prospective polarity and relapse prediction, clinically meaningful treatment matching, safe reproductive decisions, and closing an all-cause mortality gap of about twofold without reducing the problem to suicide alone (Hayes 2015, PMID 25735195; Biazus 2023, PMID 37491460).
Start here: overview. Frontier: open questions. Growth history: curation log.
Reading paths¶
| Need | Recommended path |
|---|---|
| First orientation | Overview → Diagnosis and spectrum → Epidemiology and course |
| Acute treatment | Mania and mixed states → Bipolar depression → Guidelines |
| Long-term treatment | Maintenance → Lithium → Psychotherapy and self-management |
| Controversies | Antidepressants → Biomarkers and digital phenotyping → Open questions |
| Safety and special populations | Suicide, mortality and physical health → Pregnancy and reproductive health → Red flags |
| Human and service context | Comorbidity and differential diagnosis → Patient experience and advocacy → patient-voice layer |
| Research pipeline | Genetics and neurobiology → Biomarkers → Clinical trials |
Pages¶
The canonical page list for this condition. All 18 pages were audited on 2026-09-03; subsequent sweeps leave the 11 edited pages at draft, as shown below.
| File | Scope | Status |
|---|---|---|
| overview.md | Bipolar spectrum, burden, mechanisms and treatment map | curated |
| diagnosis-and-bipolar-spectrum.md | Mania, hypomania, bipolar I/II, cyclothymia, mixed features and mimics | curated |
| epidemiology-and-course.md | Prevalence, onset, recurrence, disability, diagnostic delay and polarity | draft |
| genetics-and-neurobiology.md | Heritability, GWAS, circuits, rhythms, signaling and neurobiology | draft |
| mania-and-mixed-states.md | Acute mania, agitation, psychosis, mixed presentations and evidence | curated |
| bipolar-depression.md | Depressive episodes, differentiation from MDD and evidence-based therapies | draft |
| maintenance-and-relapse-prevention.md | Lithium, anticonvulsants, antipsychotics and polarity-specific prevention | draft |
| lithium.md | Efficacy, suicide evidence, monitoring, renal/thyroid effects and toxicity | draft |
| antidepressant-controversy.md | Switch, cycle acceleration, efficacy, subgroups and disagreement | curated |
| psychotherapy-and-self-management.md | Psychoeducation, family therapy, cognitive therapy, rhythms and digital tools | curated |
| comorbidity-and-differential-diagnosis.md | ADHD, substance use, anxiety, personality and medical mimics | draft |
| suicide-mortality-and-physical-health.md | Suicide, cardiovascular/metabolic burden and mortality gap | draft |
| pregnancy-and-reproductive-health.md | Teratogenicity, postpartum risk, lactation and comparative risk | draft |
| guidelines.md | CANMAT/ISBD, NICE, VA/DoD and international disagreements | draft |
| biomarkers-and-digital-phenotyping.md | Omics, imaging, actigraphy, speech and relapse prediction | draft |
| clinical-trials-landscape.md | Acute, maintenance, neuromodulation and precision-treatment trials | draft |
| patient-experience-and-advocacy.md | Diagnosis journey, stigma, identity, family burden and organizations | curated |
| red-flags-and-safety-concerns.md | Mania, psychosis, suicidality, toxicity and unsafe withdrawal | curated |
Literature layer¶
| Artifact | Contents | Build state |
|---|---|---|
| BIBLIOGRAPHY.md | 440 unique PubMed records plus one DOI-cited preprint; tags and citing files | 2026-10-09, 2026-10-16 and 2026-10-23 additions pending audit |
| Landmark notes | 6 structured notes: GWAS, STEP-BD, psychoeducation, maintenance, lithium/suicide and pregnancy recurrence | complete |
| Guideline registry | 34 international, national and special-purpose documents (three further ISBD task-force documents backfilled 2026-10-23); superseded chains, disagreements and watch list | 2026-10-09 through 2026-10-23 additions pending audit |
| Statistics | 166 source-locked rows across epidemiology, course, treatment, physical health and reproduction; one flagged GBD incidence conflict, re-checked and still unresolved on 2026-10-23 | 2026-10-09 through 2026-10-23 additions pending audit |
| Patient voice | Ethics/method, 13-organization directory, themes and annotated sources | Directory/themes audited; 2026-10-16 source annotations pending audit |
| Open questions | 25 stable tiered questions plus 14 “Dots not yet connected” junctions | OQ-10, OQ-14, OQ-15 and OQ-19 sharpened 2026-10-23; none closed |
Curation state¶
All 18 pages were extended on 2026-09-03 by codex and independently re-audited the same day by Claude, which re-fetched every added record, corrected eight substantive or labelling defects, replaced a stale absence statement and promoted all 18 pages to curated. The pass added quantified trials and syntheses, guideline-grade disagreements, mechanistic depth and explicit two-sided uncertainties while widening the bibliography from 304 to 393 distinct records; wiki citation breadth rose from 16.5 to 21.2 distinct records per page (297→382), so the added lines carried genuinely new evidence rather than recycling the existing pool. 2026-10-09 periodic sweep. The sweep added 31 PubMed records, one preprint and five registry records across 11 pages, which are now draft pending an independent audit by a different engine. The most consequential additions are the first bipolar-specific serial-ketamine RCT, two first-episode-mania comparative-effectiveness emulations that point in partly different directions, an externally validated RNA-editing blood test, lithium-vs-valproate suicide and mortality comparisons, and five ISBD task-force documents missing from the registry. The sweep also flagged an internal conflict: a cited GBD 2021 'incidence' count exceeds GBD prevalence. See the curation log.
2026-10-16 periodic sweep. Seven PubMed records were retained: the paired Polish antipsychotic metabolic-risk recommendations, a historical contraception survey, and four bibliography-only items for follow-up. The sweep refreshed all 38 tracked NCT records, corrected the azetukalner extension status and ALTO-100 dates, added ENERGISE-BD, COMBINER and CRiB2 from ISRCTN, and retained the WHO GBD 2023 estimate separately from the unresolved GBD 2021 conflict. Two dated Bipolar UK resources were added to the patient-voice source list. No landmark note was warranted; the three edited wiki pages remain draft pending independent audit.
2026-10-23 periodic sweep. Eight PubMed records were added. Four are inside the window: a cardiovascular-incidence meta-analysis (abstract only), a single-trust ethnic-delay cohort, a sarcopenia comparison in women, and a pediatric umbrella review’s suicide-attempt figure (abstract only). Four are earlier papers backfilled because they change a headline or fill an ISBD gap: the 2025 multi-ancestry GWAS (298 loci), the NExT activity statement, the older-adult lithium systematic review, and a vascular-imaging research agenda. Two trials were added (PolarUs, B-HAPPI) and BALSAM-2’s verification month was corrected. No landmark note was written. The six edited wiki pages were already draft and stay draft.
The unipolar depression condition retains major depressive disorder generally; treatment and risk questions specific to bipolar depression remain here.