2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/2iy5wruuedsh6.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/00yc7rcvua6a7.js","/_next/static/immutable/chunks/37ktb71aq3480.js","/_next/static/immutable/chunks/2d50b-7eu4558.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/2d6noqpp6ehas.js","/_next/static/immutable/chunks/1sx186c93bpzg.js","/_next/static/immutable/chunks/3dc-1n866s65i.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2w1bvggzb0ga8.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T882,Topiramate has been linked to increased glaucoma risk, potentially through mechanisms involving ocular fluid shifts. However, comparative risks vs other antiseizure medications (ASMs) and variation by sex or indication remain uncertain. This study evaluates glaucoma incidence in topiramate initiators compared to valproate or lamotrigine users among patients with epilepsy or migraine. We conducted a retrospective active-comparator, new-user cohort study using electronic health records from the IQVIA Medical Research Data among patients with epilepsy or migraine initiating topiramate, valproate, or lamotrigine. Patients with prior ASM use, limited washout period and follow-up, or pre-existing glaucoma were excluded. The outcome was incident glaucoma within 1 year, censored at glaucoma occurrence, death, discontinuation, switch, or September 30, 2023. Covariates included age, sex, race, lifestyle factors, comorbidities, and medication history. Propensity score-based inverse probability weighting balanced characteristics, and crude and weighted Cox models estimated hazard ratios (HRs) with 95% confidence intervals (CIs). Subgroup analyses were conducted by sex, age, and indication. The cohort included 688 topiramate, 4490 valproate, and 4179 lamotrigine initiators. After weighting, the 1-year absolute risk increase was approximately 2.4% when comparing topiramate to valproate, and about 2.0% compared to lamotrigine. Topiramate was associated with higher glaucoma risk vs valproate (adjusted HR 2.66, 95% CI 1.12-6.32) and lamotrigine (adjusted HR 3.57, 95% CI 1.76-7.26). Risks were elevated in female (vs valproate: HR 5.31, 95% CI 1.48-19.08; vs lamotrigine: HR 5.73, 95% CI 2.38-13.79) or epilepsy patients (vs valproate: HR 2.23, 95% CI 1.04-4.76; vs lamotrigine: HR 5.08, 95% CI 2.32-11.14), but not in male or migraine patients. Topiramate use substantially increases glaucoma risk compared with valproate and lamotrigine, particularly among female or epilepsy patients. No significant association in male or migraine patients was observed. These findings may inform targeted ophthalmologic monitoring in high-risk groups and use of alternative ASMs.31:Tb19,Abstract Objective Topiramate has been linked to increased glaucoma risk, potentially through mechanisms involving ocular fluid shifts. However, comparative risks vs other antiseizure medications (ASMs) and variation by sex or indication remain uncertain. This study evaluates glaucoma incidence in topiramate initiators compared to valproate or lamotrigine users among patients with epilepsy or migraine. Methods We conducted a retrospective active‐comparator, new‐user cohort study using electronic health records from the IQVIA Medical Research Data among patients with epilepsy or migraine initiating topiramate, valproate, or lamotrigine. Patients with prior ASM use, limited washout period and follow‐up, or pre‐existing glaucoma were excluded. The outcome was incident glaucoma within 1 year, censored at glaucoma occurrence, death, discontinuation, switch, or September 30, 2023. Covariates included age, sex, race, lifestyle factors, comorbidities, and medication history. Propensity score–based inverse probability weighting balanced characteristics, and crude and weighted Cox models estimated hazard ratios (HRs) with 95% confidence intervals (CIs). Subgroup analyses were conducted by sex, age, and indication. Results The cohort included 688 topiramate, 4490 valproate, and 4179 lamotrigine initiators. After weighting, the 1‐year absolute risk increase was approximately 2.4% when comparing topiramate to valproate, and about 2.0% compared to lamotrigine. Topiramate was associated with higher glaucoma risk vs valproate (adjusted HR 2.66, 95% CI 1.12–6.32) and lamotrigine (adjusted HR 3.57, 95% CI 1.76–7.26). Risks were elevated in female (vs valproate: HR 5.31, 95% CI 1.48–19.08; vs lamotrigine: HR 5.73, 95% CI 2.38–13.79) or epilepsy patients (vs valproate: HR 2.23, 95% CI 1.04–4.76; vs lamotrigine: HR 5.08, 95% CI 2.32–11.14), but not in male or migraine patients. Significance Topiramate use substantially increases glaucoma risk compared with valproate and lamotrigine, particularly among female or epilepsy patients. No significant association in male or migraine patients was observed. These findings may inform targeted ophthalmologic monitoring in high‐risk groups and use of alternative ASMs. 25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"valproate: generic Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on valproate (generic). Clinician-written summaries and actionable practice insights. 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Adults","journal_title":"Neurology","journal_issn":"0028-3878","published_at":"2026-08-31T00:00:00.000Z","url":"https://doi.org/10.1212/wnl.0000000000218112","source_score":15,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-04T06:22:23.456Z","updated_at":"2026-09-04T06:22:23.456Z","tags":[{"paper_doi":"10.1212/wnl.0000000000218112","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218112","tag_type":"brand","value":"Aimovig","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218112","tag_type":"brand","value":"Ajovy","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218112","tag_type":"brand","value":"Botox","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218112","tag_type":"brand","value":"Emgality","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218112","tag_type":"brand","value":"Nurtec ODT","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218112","tag_type":"brand","value":"Qulipta","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218112","tag_type":"brand","value":"Vyepti","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218112","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218112","tag_type":"condition","value":"Chronic Migraine","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218112","tag_type":"condition","value":"Episodic 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Blocker","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218112","tag_type":"modality","value":"Botulinum Toxin","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218112","tag_type":"modality","value":"Calcium Channel Blocker","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218112","tag_type":"modality","value":"CGRP Monoclonal Antibody","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218112","tag_type":"modality","value":"CGRP Receptor Antagonist (Gepant)","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218112","tag_type":"modality","value":"Tricyclic Antidepressant","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218112","tag_type":"sample_size","value":"n=217","value_numeric":217},{"paper_doi":"10.1212/wnl.0000000000218112","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218112","tag_type":"study_design","value":"Systematic Review","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218112","tag_type":"warning","value":"Head-to-head comparative effectiveness data were generally low or very low confidence; rankings among agents should not be inferred from this review alone.","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218112","tag_type":"warning","value":"Sample size tag reflects number of included studies (n=217 RCTs), not total patient participants — total patient N is not reported in the abstract.","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218112","tag_type":"warning","value":"The 'practice_changing' impact flag reflects the role of this SR in informing a new AAN/AHS guideline; direct clinical recommendations are in a separate companion publication not reviewed here.","value_numeric":null}],"summaries":{"what_studied":"This systematic review of 217 RCTs evaluated pharmacologic prevention for episodic and chronic migraine in adults, comparing active agents to placebo across outcomes including monthly headache days, ≥50% responder rates, and validated quality-of-life (QOL) measures (searches through June 2024).","key_result":"For **episodic migraine**, high-confidence evidence favored galcanezumab and erenumab over placebo; moderate-confidence evidence supported atogepant, eptinezumab, fremanezumab, propranolol, topiramate, and valproate. For **chronic migraine**, high-confidence evidence supported fremanezumab, galcanezumab, and onabotulinumtoxinA; moderate-confidence evidence supported atogepant, eptinezumab, erenumab, topiramate, and valproate. Head-to-head comparisons were limited and generally low or very low confidence.","limitations":"- No reliable head-to-head comparative effectiveness data; most evidence is placebo-controlled only.\n- Evidence certainty for many oral agents (e.g., amitriptyline, metoprolol, flunarizine) was low, limiting firm conclusions.\n- The review does not address tolerability, long-term safety, or cost-effectiveness in detail.","practice_takeaway":"For adults needing migraine prevention, CGRP-pathway agents (erenumab, galcanezumab, fremanezumab, eptinezumab, atogepant) now have the strongest evidence base alongside onabotulinumtoxinA for chronic migraine. Clinicians choosing among agents should reference the companion AAN/AHS guideline for individualized recommendations, as head-to-head data to guide sequencing remain sparse."}},{"doi":"10.1212/wnl.0000000000218375","pmid":"42617146","title":"Paternal Valproate Exposure and Offspring Neurodevelopmental Outcomes","journal_title":"Neurology","journal_issn":"0028-3878","published_at":"2026-08-19T00:00:00.000Z","url":"https://doi.org/10.1212/wnl.0000000000218375","source_score":39,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-24T06:18:26.926Z","updated_at":"2026-08-24T06:18:26.926Z","tags":[{"paper_doi":"10.1212/wnl.0000000000218375","tag_type":"age_group","value":"pediatric","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218375","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218375","tag_type":"condition","value":"Autism Spectrum Disorder","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218375","tag_type":"condition","value":"Congenital Malformations","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218375","tag_type":"condition","value":"Epilepsy","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218375","tag_type":"condition","value":"Neurodevelopmental Disorders","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218375","tag_type":"generic","value":"lamotrigine","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218375","tag_type":"generic","value":"levetiracetam","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218375","tag_type":"generic","value":"valproate","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218375","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218375","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218375","tag_type":"modality","value":"Antiseizure Medication","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218375","tag_type":"sample_size","value":"n=14998","value_numeric":14998},{"paper_doi":"10.1212/wnl.0000000000218375","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218375","tag_type":"study_design","value":"Retrospective Population-Based Cohort Study","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218375","tag_type":"warning","value":"PS-weighted adjusted OR for congenital malformations could not be pooled due to model non-convergence in Norway, limiting conclusions about CM risk.","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218375","tag_type":"warning","value":"The Nordic PASS NDD finding is driven largely by the meta-analysis of propensity score–weighted models; crude country-level HRs were non-significant in all three countries. The statistical significance is sensitive to the modeling approach and differences in follow-up time between exposure groups.","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218375","tag_type":"warning","value":"The Taiwanese study described in the abstract found NO increased NDD risk (HR ~0.86–1.02 across subtypes), which directly contrasts with the Nordic PASS pooled finding of HR 1.50. Clinicians should note these conflicting results from different populations.","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218375","tag_type":"warning","value":"This is a corrigendum (corrected final report v1.0, October 2023) to a PASS submitted to the EMA PRAC — not the 2026 Neurology publication cited in the abstract metadata. The full-text content reflects the Nordic PASS report, while the abstract describes a separate Taiwanese cohort study (n=2,583,503) with null findings. These are two distinct studies; the structured output primarily reflects the Nordic PASS data in the full text.","value_numeric":null}],"summaries":{"what_studied":"This post-authorisation safety study (PASS) assessed whether paternal exposure to valproate monotherapy during spermatogenesis (3 months before conception) is associated with neurodevelopmental disorders (NDDs) or congenital malformations (CM) in offspring, compared to paternal exposure to lamotrigine or levetiracetam monotherapy. Data came from national registries in Denmark, Sweden, and Norway, covering pregnancies from the late 1990s through 2019.","key_result":"In the meta-analysis of propensity score–weighted Cox models across all 3 countries, paternal valproate exposure was associated with a significantly higher risk of composite NDD (including ASD) compared to lamotrigine/levetiracetam (pooled PS-weighted HR 1.50, 95% CI 1.09–2.07). Country-specific PS-weighted HRs were non-significant individually (Denmark 1.34 [0.79–2.25], Sweden 1.54 [0.95–2.51], Norway 1.76 [0.83–3.71]). No higher risk of congenital malformations was found (crude pooled OR 0.81, 95% CI 0.48–1.36); adjusted OR could not be pooled due to model non-convergence in Norway.","limitations":"- Shorter follow-up in the lamotrigine/levetiracetam group versus valproate group (especially in Denmark and Sweden) may have inflated NDD detection in the valproate group, as year of conception was earlier for valproate-exposed fathers.\n- Confounding by indication could not be fully excluded; severity of epilepsy or psychiatric disorder was not captured in registry data.\n- The NDD outcome was a broad composite; individual subtypes (ASD, ADHD, ID) could not be reliably analyzed separately due to small event counts.","practice_takeaway":"Clinicians should be aware that this large Nordic PASS found a statistically significant ~50% higher pooled risk of composite NDDs in children of fathers who used valproate near conception compared to those using lamotrigine or levetiracetam, though individual country estimates were non-significant and important confounding limitations remain. Counseling men of reproductive age on valproate should acknowledge this signal while noting that further confirmatory evidence is needed before changing practice."}},{"doi":"10.1136/bmj-2026-100216","pmid":"42580772","title":"Evidence based interventions for bipolar disorder across phases and age groups: living umbrella review, evaluation, analysis, and communication hub (U-REACH) project","journal_title":"BMJ","journal_issn":"1756-1833","published_at":"2026-08-11T00:00:00.000Z","url":"https://doi.org/10.1136/bmj-2026-100216","source_score":89,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-17T13:33:30.432Z","updated_at":"2026-08-17T13:33:30.432Z","tags":[{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"brand","value":"Caplyta","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"brand","value":"Latuda","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"brand","value":"Vraylar","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"category","value":"Medicine, General & Internal","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"condition","value":"Bipolar Disorder","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"aripiprazole","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"asenapine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"carbamazepine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"cariprazine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"divalproex","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"fluoxetine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"haloperidol","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"ketamine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"lamotrigine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"lithium","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"lumateperone","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"lurasidone","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"olanzapine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"paliperidone","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"quetiapine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"risperidone","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"tamoxifen","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"valproate","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"ziprasidone","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"modality","value":"Atypical Antipsychotic","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"modality","value":"Brain Stimulation","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"modality","value":"Mood Stabilizer","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"modality","value":"NMDA Receptor Antagonist","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"modality","value":"Nutraceutical","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"modality","value":"Psychosocial Intervention","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"sample_size","value":"n=77","value_numeric":77},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"study_design","value":"Umbrella Review (Living Systematic Review with Meta-Analyses)","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"warning","value":"Study design label 'Umbrella Review' is a non-standard design category; it is a higher-order synthesis above standard systematic reviews and meta-analyses.","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"warning","value":"Tamoxifen is listed as effective for adult mania — this is an uncommon clinical use (PKC inhibition mechanism) and may surprise readers unfamiliar with this evidence base.","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"warning","value":"The 'practice_changing' impact flag is applied because this is a comprehensive living umbrella review with an open-access clinical decision tool, though individual treatment effect sizes are not extractable from the abstract alone.","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"warning","value":"The sample_size tag reflects the number of included systematic reviews (n=77), not individual patient-level N, which is not reported as a single aggregate in the abstract.","value_numeric":null}],"summaries":{"what_studied":"A living umbrella review (U-REACH) evaluated the certainty of evidence for pharmacological, nutraceutical, psychosocial, brain stimulation, and circadian rhythm-based treatments across all bipolar disorder phases (depression, mania/mixed, maintenance) and age groups (adults; children/adolescents), using 77 systematic reviews (21 network meta-analyses, 56 pairwise meta-analyses) published up to November 2024.","key_result":"Across 2,510 meta-analyses covering 133 outcomes and 116 unique treatments, GRADE ratings were high (n=236), moderate (n=827), low (n=986), and very low (n=461). Agents effective across multiple phases in adults included aripiprazole, asenapine, cariprazine, divalproex/valproate, lamotrigine, lithium, olanzapine, paliperidone, quetiapine, and risperidone; in youth, lurasidone and olanzapine-fluoxetine were supported for bipolar depression, and aripiprazole, asenapine, olanzapine, quetiapine, and risperidone for mania.","limitations":"Most evidence is rated low or very low certainty (1,447 of 2,510 meta-analyses), limiting confidence in many treatment estimates; the umbrella review design inherits limitations of the included meta-analyses (e.g., heterogeneity, publication bias); pediatric data are sparse compared with adult data.","practice_takeaway":"Use the freely available EBI-BD platform (ebibd-database.org) to identify phase- and age-specific evidence-based options and discuss patient-preferred safety profiles using its 12-intervention, 17-outcome preference tool. For cross-phase adult coverage, lithium, quetiapine, olanzapine, aripiprazole, and divalproex/valproate have the broadest support; for youth, lurasidone (bipolar depression) and aripiprazole (mania) have the strongest pediatric evidence."}},{"doi":"10.1136/jnnp-2026-338454","pmid":"42120066","title":"Risk of neurodevelopmental disorders associated with paternal use of valproate during spermatogenesis: a living meta-analysis—version 1","journal_title":"Journal of Neurology, Neurosurgery & Psychiatry","journal_issn":"0022-3050","published_at":"2026-05-12T00:00:00.000Z","url":"https://doi.org/10.1136/jnnp-2026-338454","source_score":20,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-14T13:22:55.671Z","updated_at":"2026-05-14T13:22:55.671Z","tags":[{"paper_doi":"10.1136/jnnp-2026-338454","tag_type":"age_group","value":"pediatric","value_numeric":null},{"paper_doi":"10.1136/jnnp-2026-338454","tag_type":"category","value":"Surgery","value_numeric":null},{"paper_doi":"10.1136/jnnp-2026-338454","tag_type":"condition","value":"Epilepsy","value_numeric":null},{"paper_doi":"10.1136/jnnp-2026-338454","tag_type":"condition","value":"Neurodevelopmental Disorders","value_numeric":null},{"paper_doi":"10.1136/jnnp-2026-338454","tag_type":"generic","value":"lamotrigine","value_numeric":null},{"paper_doi":"10.1136/jnnp-2026-338454","tag_type":"generic","value":"levetiracetam","value_numeric":null},{"paper_doi":"10.1136/jnnp-2026-338454","tag_type":"generic","value":"valproate","value_numeric":null},{"paper_doi":"10.1136/jnnp-2026-338454","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1136/jnnp-2026-338454","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1136/jnnp-2026-338454","tag_type":"modality","value":"Antiseizure Medication","value_numeric":null},{"paper_doi":"10.1136/jnnp-2026-338454","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1136/jnnp-2026-338454","tag_type":"study_design","value":"Living Systematic Review and Meta-Analysis","value_numeric":null},{"paper_doi":"10.1136/jnnp-2026-338454","tag_type":"warning","value":"The 'living meta-analysis' design means findings are version 1 and subject to update; current conclusions are based on only 3 studies. Confidence intervals are wide and do not rule out modest effects.","value_numeric":null},{"paper_doi":"10.1136/jnnp-2026-338454","tag_type":"warning","value":"Total sample size (N) across included studies is not reported in the abstract; the sample_size tag has been omitted accordingly.","value_numeric":null},{"paper_doi":"10.1136/jnnp-2026-338454","tag_type":"warning","value":"Two of the three included studies overlap on Norwegian registry data (Norway 1 and Norway 2), requiring split meta-analyses rather than a single pooled estimate — interpret pooled HRs with this structural limitation in mind.","value_numeric":null}],"summaries":{"what_studied":"This living meta-analysis evaluated whether paternal valproate use during spermatogenesis (vs. lamotrigine or levetiracetam) raises the risk of neurodevelopmental disorders (NDDs) in offspring, pooling data from 3 observational studies across Norway, Sweden, Denmark, and Taiwan (searched January 1995–October 2025).","key_result":"No significant association was found: pooled HRs ranged from 1.03–1.06 across all meta-analytic combinations (e.g., HR 1.05, 95% CI 0.87–1.27; I²=0.0%), with no heterogeneity detected.","limitations":"- Only 3 eligible studies were identified, all observational and registry-based, limiting causal inference.\n- Two studies shared Norwegian data (Norway 1 and Norway 2), requiring separate analyses to avoid double-counting.\n- Generalizability beyond Scandinavian/Taiwanese populations is uncertain.","practice_takeaway":"Current evidence does not support increased NDD risk in children fathered by men taking valproate during spermatogenesis compared to those on lamotrigine or levetiracetam. Clinicians can note this reassuring signal, but should monitor updates as this is a living review designed for revision as new data emerge."}},{"doi":"10.1192/bjp.2026.10636","pmid":"42057566","title":"Real-world effectiveness of mono- and combination therapies of mood stabilisers and antipsychotics in bipolar disorder: nationwide, within-individual study of 315 046 patients","journal_title":"The British Journal of Psychiatry","journal_issn":"0007-1250","published_at":"2026-04-30T00:00:00.000Z","url":"https://doi.org/10.1192/bjp.2026.10636","source_score":32,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-08T13:23:56.711Z","updated_at":"2026-05-08T13:23:56.711Z","tags":[{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"category","value":"Psychiatry","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"condition","value":"Bipolar Disorder","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"generic","value":"aripiprazole","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"generic","value":"brexpiprazole","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"generic","value":"carbamazepine","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"generic","value":"lamotrigine","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"generic","value":"lithium","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"generic","value":"lurasidone","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"generic","value":"olanzapine","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"generic","value":"paliperidone","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"generic","value":"quetiapine","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"generic","value":"risperidone","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"generic","value":"sulpiride","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"generic","value":"valproate","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"generic","value":"zotepine","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"modality","value":"Antipsychotic","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"modality","value":"Long-Acting Injectable Antipsychotic","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"modality","value":"Mood Stabiliser","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"sample_size","value":"n=315,046","value_numeric":315046},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"study_design","value":"Population-Based Cohort Study (Within-Individual Design)","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"warning","value":"Findings are from a Japanese population where lithium prescribing rates (~47%) are much higher than in Western countries (~16–17%), which may affect transportability.","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"warning","value":"Impact flag 'practice_changing' applied due to first systematic real-world evaluation of combination regimens in this scale, but the observational design warrants caution before changing practice.","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"warning","value":"The study could not distinguish hospitalisation due to mania, depression, or other psychiatric causes, limiting interpretation of episode-specific effectiveness.","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"warning","value":"The study population required ≥2 lifetime lithium prescriptions, which may overrepresent lithium-eligible patients and limit generalisability to those never prescribed lithium.","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10636","tag_type":"warning","value":"Zotepine is not approved in the US or EU; clinicians in these regions cannot act on zotepine findings directly.","value_numeric":null}],"summaries":{"what_studied":"This nationwide, population-based cohort study used a within-individual design to compare mono- and combination therapy with mood stabilisers (lithium, valproate, lamotrigine, carbamazepine) and 33+ antipsychotics in 315,046 Japanese adults with bipolar disorder, measuring time to psychiatric hospitalisation over a median 7.1-year follow-up (April 2013–May 2023).","key_result":"All four mood stabiliser monotherapies reduced hospitalisation risk vs. non-use: lithium was strongest (aHR 0.67), followed by valproate (0.71), lamotrigine (0.72), and carbamazepine (0.74). Among antipsychotics, sultopride showed the greatest reduction (aHR 0.53), with aripiprazole LAI (0.62) and oral aripiprazole (0.73) also performing well; quetiapine showed only modest benefit (aHR 0.82), which was dose-dependent (≥300 mg/day: 0.75 vs. <300 mg/day: 0.85). Combination therapy further reduced risk: lithium + carbamazepine (aHR 0.73) and lithium + zotepine (0.82) outperformed lithium alone; lithium + sulpiride increased risk (aHR 1.16). Aripiprazole consistently added benefit across all mood stabiliser backbones (lithium, valproate, lamotrigine).","limitations":"- Residual confounding by indication remains (medications often started during clinical deterioration); the within-individual design reduces but does not eliminate this.\n- Prescription records may not reflect actual adherence; no therapeutic drug monitoring data available.\n- Reason for hospitalisation (mania vs. depression vs. other) could not be determined from reimbursement data.","practice_takeaway":"Lithium remains the most effective mood stabiliser for preventing psychiatric hospitalisation, and adding aripiprazole to any first-line mood stabiliser consistently provides further benefit. Clinicians should be cautious with sulpiride as an add-on to lithium (associated with increased risk) and note that low-dose quetiapine (<300 mg/day) offers minimal protection."}},{"doi":"10.1002/epi.70087","pmid":"41518480","title":"Sex‐specific elevated incidence of glaucoma associated with topiramate versus valproate or lamotrigine in epilepsy, not migraine: A population‐based cohort study","journal_title":"Epilepsia","journal_issn":"0013-9580","published_at":"2026-01-10T00:00:00.000Z","url":"https://doi.org/10.1002/epi.70087","source_score":30,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-01-11","doi":"10.1002/epi.70087","days":"7","issn":"0013-9580","rank":"10","field":"Clinical Medicine","score":"30","category":"Clinical Neurology","categories":["Clinical Neurology"],"_categories":["Clinical Neurology"]},"pubmed":{"doi":"10.1002/epi.70087","title":"Sex-specific elevated incidence of glaucoma associated with topiramate versus valproate or lamotrigine in epilepsy, not migraine: A population-based cohort study.","journal":"Epilepsia","methods":"","results":"The cohort included 688 topiramate, 4490 valproate, and 4179 lamotrigine initiators. After weighting, the 1-year absolute risk increase was approximately 2.4% when comparing topiramate to valproate, and about 2.0% compared to lamotrigine. Topiramate was associated with higher glaucoma risk vs valproate (adjusted HR 2.66, 95% CI 1.12-6.32) and lamotrigine (adjusted HR 3.57, 95% CI 1.76-7.26). Risks were elevated in female (vs valproate: HR 5.31, 95% CI 1.48-19.08; vs lamotrigine: HR 5.73, 95% CI 2.38-13.79) or epilepsy patients (vs valproate: HR 2.23, 95% CI 1.04-4.76; vs lamotrigine: HR 5.08, 95% CI 2.32-11.14), but not in male or migraine patients.","abstract":"$30","keywords":["glaucoma","lamotrigine","topiramate","valproate"],"pubmed_id":"41518480","conclusions":"","publication_date":"2026-01-10T00:00:00"},"crossref":{"DOI":"10.1002/epi.70087","URL":"https://doi.org/10.1002/epi.70087","ISSN":["0013-9580","1528-1167"],"link":[{"URL":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/epi.70087","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":null,"score":1,"title":["Sex‐specific elevated incidence of glaucoma associated with topiramate versus valproate or lamotrigine in epilepsy, not migraine: A population‐based cohort study"],"author":[{"given":"Cuiling","family":"Wei","sequence":"first","affiliation":[{"name":"Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong SAR China"}]},{"given":"Rachel Yui Ki","family":"Chu","sequence":"additional","affiliation":[{"name":"Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong SAR China"}]},{"given":"Rachel Lancey","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology The Chinese University of Hong Kong & Prince of Wales Hospital Hong Kong SAR China"}]},{"given":"Florinda Hui‐Ning","family":"Chu","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Medicine, Queen Mary Hospital University of Hong Kong Hong Kong SAR China"}]},{"given":"Ian Yu Hin","family":"Leung","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Medicine, Queen Mary Hospital University of Hong Kong Hong Kong SAR China"}]},{"given":"William Chun Yin","family":"Leung","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Medicine, Queen Mary Hospital University of Hong Kong Hong Kong SAR China"}]},{"given":"Franco Wing Tak","family":"Cheng","sequence":"additional","affiliation":[{"name":"Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong SAR China"},{"name":"Pharmacy Department Gleneagles Hong Kong Hospital Hong Kong SAR China"},{"name":"Department of Pharmacy The University of Hong Kong‐Shenzhen Hospital Shenzhen China"}]},{"given":"Thomas Chi Ho","family":"Lam","sequence":"additional","affiliation":[{"name":"Hong Kong Eye Hospital Hong Kong SAR China"},{"name":"Department of Ophthalmology and Visual Sciences The Chinese University of Hong Kong Hong Kong SAR China"}]},{"given":"Ian Chi Kei","family":"Wong","sequence":"additional","affiliation":[{"name":"Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong SAR China"},{"name":"Aston School of Pharmacy Aston University Birmingham UK"},{"name":"Laboratory of Data Discovery for Health (D²4H) Hong Kong Science Park Hong Kong SAR China"}]},{"given":"Esther Wai Yin","family":"Chan","sequence":"additional","affiliation":[{"name":"Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong SAR China"},{"name":"Department of Pharmacy The University of Hong Kong‐Shenzhen Hospital Shenzhen China"},{"name":"Laboratory of Data Discovery for Health (D²4H) Hong Kong Science Park Hong Kong SAR China"},{"name":"The University of Hong Kong Shenzhen Institute of Research and Innovation Shenzhen China"}]},{"given":"Francisco Tsz Tsun","family":"Lai","sequence":"additional","affiliation":[{"name":"Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong SAR China"},{"name":"Laboratory of Data Discovery for Health (D²4H) Hong Kong Science Park Hong Kong SAR China"},{"name":"Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong SAR China"}]}],"issued":{"date-parts":[[2026,1,10]]},"member":"311","prefix":"10.1002","source":"Crossref","volume":null,"archive":["Portico"],"created":{"date-time":"2026-01-10T15:26:37Z","timestamp":1768058797000,"date-parts":[[2026,1,10]]},"indexed":{"date-time":"2026-01-10T18:17:07Z","timestamp":1768069027497,"date-parts":[[2026,1,10]]},"license":[{"URL":"http://creativecommons.org/licenses/by/4.0/","start":{"date-time":"2026-01-10T00:00:00Z","timestamp":1768003200000,"date-parts":[[2026,1,10]]},"delay-in-days":0,"content-version":"vor"}],"subject":[],"abstract":"$31","language":"en","relation":{},"resource":{"primary":{"URL":"https://onlinelibrary.wiley.com/doi/10.1002/epi.70087"}},"subtitle":[],"assertion":[{"name":"received","group":{"name":"publication_history","label":"Publication History"},"label":"Received","order":0,"value":"2025-10-06"},{"name":"accepted","group":{"name":"publication_history","label":"Publication 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use and pre-existing glaucoma.","key_result":"After weighting, the 1-year absolute risk increase was ~2.4% versus valproate and ~2.0% versus lamotrigine; adjusted HRs were 2.66 (95% CI 1.12-6.32) versus valproate and 3.57 (95% CI 1.76-7.26) versus lamotrigine. Elevated risks were seen in females (HR 5.31 vs valproate; 5.73 vs lamotrigine) and in epilepsy (HR 2.23 vs valproate; 5.08 vs lamotrigine), but not in males or migraine.","limitations":"Follow-up was limited to 1 year. The topiramate group was relatively small (n=688), and subgroup estimates had wide confidence intervals.","practice_takeaway":"For epilepsy—especially in women—topiramate was linked to higher 1-year glaucoma risk than valproate or lamotrigine; consider alternative ASMs or closer ophthalmic monitoring. No increased risk was detected in men or in migraine patients in this dataset."}}],"initialOffset":6,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"generic","value":"valproate"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Generics","href":"/hub/tag/generic"},{"name":"valproate"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"generic","hub_tag_value":"valproate"}}}]]

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