diff --git a/domains/health/glp1-eating-disorder-pharmacovigilance-signal-class-effect-obesity-population-specific.md b/domains/health/glp1-eating-disorder-pharmacovigilance-signal-class-effect-obesity-population-specific.md new file mode 100644 index 000000000..997e36420 --- /dev/null +++ b/domains/health/glp1-eating-disorder-pharmacovigilance-signal-class-effect-obesity-population-specific.md @@ -0,0 +1,19 @@ +--- +type: claim +domain: health +description: VigiBase analysis of 2.06M reports shows eating disorder signal across all three GLP-1 RAs only after Wegovy obesity approval, suggesting risk is dose-dependent or population-selection-dependent rather than drug-specific +confidence: experimental +source: VigiBase WHO database, Clinical Nutrition 2025 +created: 2026-05-04 +title: GLP-1 eating disorder pharmacovigilance signal (aROR 4.17-6.80) is a class effect that emerged specifically in the obesity treatment population after June 2021, not in the prior metabolic population +agent: vida +sourced_from: health/2025-xx-vigibase-glp1-psychiatric-adverse-events-eating-disorders.md +scope: causal +sourcer: Clinical Nutrition / VigiBase WHO +supports: ["glp1-discontinuation-predicted-by-psychiatric-comorbidity-creating-access-adherence-trap", "glp1-pre-treatment-eating-disorder-screening-recommended-not-required"] +related: ["glp1-eating-disorder-risk-subtype-specific-protective-bed-harmful-restrictive", "glp1-pre-treatment-eating-disorder-screening-recommended-not-required", "glp1-psychiatric-effects-directionally-opposite-metabolic-versus-psychiatric-populations", "glp1-receptor-agonists-demonstrate-superior-efficacy-for-alcohol-use-disorder-in-comorbid-obesity-population", "semaglutide-reduces-depression-worsening-44-percent-in-diagnosed-patients-through-glp1r-psychiatric-mechanism", "glp1-anorexia-nervosa-evidence-absent-despite-pharmacovigilance-signal"] +--- + +# GLP-1 eating disorder pharmacovigilance signal (aROR 4.17-6.80) is a class effect that emerged specifically in the obesity treatment population after June 2021, not in the prior metabolic population + +Analysis of 2,061,901 adverse event reports through December 2024 found eating disorder signals with adjusted Reporting Odds Ratios between 4.17 and 6.80 across dulaglutide, semaglutide, and liraglutide—the highest magnitude psychiatric signal in the study. Critically, sensitivity analysis revealed NO signals before June 4, 2021 (Wegovy obesity approval date), despite years of prior metabolic use for T2D. This temporal boundary indicates the risk emerged specifically in the obesity treatment population, not in metabolic patients. The class-effect finding (all three agents, not just semaglutide) suggests a pharmacological mechanism rather than drug-specific properties. The post-Wegovy emergence implies the risk is either: (a) dose-dependent (higher weight-loss doses vs. metabolic doses), or (b) population-selection-dependent (patients seeking weight management have higher ED vulnerability or undetected ED histories). Key limitation: the database lacked information on pre-existing psychiatric conditions, preventing distinction between medicine-induced reactions and indication bias. The aROR magnitude (4.17-6.80) represents 4-7x higher reporting odds compared to other drugs, making this the strongest psychiatric signal in GLP-1 pharmacovigilance. diff --git a/domains/health/glp1-pre-treatment-eating-disorder-screening-recommended-not-required.md b/domains/health/glp1-pre-treatment-eating-disorder-screening-recommended-not-required.md index d9ddccdf4..3dae8dc8e 100644 --- a/domains/health/glp1-pre-treatment-eating-disorder-screening-recommended-not-required.md +++ b/domains/health/glp1-pre-treatment-eating-disorder-screening-recommended-not-required.md @@ -11,7 +11,7 @@ sourced_from: health/2025-11-xx-mdpi-nutrients-glp1-appetite-eating-disorders-ps scope: structural sourcer: MDPI Nutrients supports: ["ai-telehealth-glp1-prescribing-commoditizes-at-scale-but-generates-systematic-safety-and-fraud-failures"] -related: ["glp1-therapy-requires-nutritional-monitoring-infrastructure-but-92-percent-receive-no-dietitian-support", "glp1-eating-disorder-risk-subtype-specific-protective-bed-harmful-restrictive"] +related: ["glp1-therapy-requires-nutritional-monitoring-infrastructure-but-92-percent-receive-no-dietitian-support", "glp1-eating-disorder-risk-subtype-specific-protective-bed-harmful-restrictive", "glp1-pre-treatment-eating-disorder-screening-recommended-not-required"] --- # Pre-treatment eating disorder screening is recommended by clinical reviews but not required by any professional guideline or regulatory body despite 4-7x elevated pharmacovigilance risk @@ -24,3 +24,10 @@ This review provides detailed clinical recommendations for eating disorder risk **Source:** PMC/Journal of Clinical Medicine systematic review, 2025 Review explicitly states 'no definitive evidence of the causal relationship between use of GLP-1 RAs in humans and development of psychiatric adverse events' regarding eating disorders specifically, and calls for pre/post-treatment psychological assessment and screening for high-risk ED patients before initiating, but notes these are recommendations not requirements. + + +## Supporting Evidence + +**Source:** VigiBase 2.06M reports, aROR analysis + +VigiBase analysis quantifies eating disorder signal magnitude at aROR 4.17-6.80 (4-7x higher reporting odds), the highest psychiatric signal in the study. However, database lacked pre-existing psychiatric condition data, preventing distinction between medicine-induced reactions and indication bias—supporting screening recommendation but not mandate. diff --git a/domains/health/glp1-psychiatric-effects-directionally-opposite-metabolic-versus-psychiatric-populations.md b/domains/health/glp1-psychiatric-effects-directionally-opposite-metabolic-versus-psychiatric-populations.md index 2c039f12d..d7944df6a 100644 --- a/domains/health/glp1-psychiatric-effects-directionally-opposite-metabolic-versus-psychiatric-populations.md +++ b/domains/health/glp1-psychiatric-effects-directionally-opposite-metabolic-versus-psychiatric-populations.md @@ -10,7 +10,7 @@ agent: vida sourced_from: health/2026-05-03-clinical-trial-vanguard-glp1-psychiatric-both-directions.md scope: causal sourcer: Clinical Trial Vanguard -related: ["clinical-ai-bias-amplification-creates-compounding-disparity-risk-at-scale", "glp1-discontinuation-predicted-by-psychiatric-comorbidity-creating-access-adherence-trap", "glp1-receptor-agonists-address-substance-use-disorders-through-mesolimbic-dopamine-modulation", "glp1-psychiatric-effects-directionally-opposite-metabolic-versus-psychiatric-populations", "semaglutide-reduces-depression-worsening-44-percent-in-diagnosed-patients-through-glp1r-psychiatric-mechanism"] +related: ["clinical-ai-bias-amplification-creates-compounding-disparity-risk-at-scale", "glp1-discontinuation-predicted-by-psychiatric-comorbidity-creating-access-adherence-trap", "glp1-receptor-agonists-address-substance-use-disorders-through-mesolimbic-dopamine-modulation", "glp1-psychiatric-effects-directionally-opposite-metabolic-versus-psychiatric-populations", "semaglutide-reduces-depression-worsening-44-percent-in-diagnosed-patients-through-glp1r-psychiatric-mechanism", "glp1-eating-disorder-risk-subtype-specific-protective-bed-harmful-restrictive"] --- # GLP-1 psychiatric effects are directionally opposite in metabolic versus psychiatric disease patients — protective in metabolic cohorts but potentially harmful in severe psychiatric comorbidity with concurrent psychotropic use @@ -23,3 +23,10 @@ The GLP-1 psychiatric safety paradox resolves through population stratification **Source:** WHO guideline 2025-12-01, absence of psychiatric contraindications WHO guideline excludes only pregnant women as explicit contraindication, with no mention of psychiatric comorbidity screening despite documented eating disorder signal (aROR 4.17-6.80) and evidence that psychiatric populations show different response patterns. This suggests regulatory guidance has not incorporated psychiatric population stratification. + + +## Supporting Evidence + +**Source:** VigiBase temporal analysis, Clinical Nutrition 2025 + +Sensitivity analysis of 2.06M VigiBase reports found NO eating disorder signals before June 4, 2021 (Wegovy obesity approval) despite years of metabolic use, confirming psychiatric effects differ between metabolic and obesity treatment populations. The temporal boundary provides strongest evidence yet for population-specific psychiatric risk profiles. diff --git a/domains/health/semaglutide-reduces-depression-worsening-44-percent-in-diagnosed-patients-through-glp1r-psychiatric-mechanism.md b/domains/health/semaglutide-reduces-depression-worsening-44-percent-in-diagnosed-patients-through-glp1r-psychiatric-mechanism.md index 08d89dfc3..4b1ea15b8 100644 --- a/domains/health/semaglutide-reduces-depression-worsening-44-percent-in-diagnosed-patients-through-glp1r-psychiatric-mechanism.md +++ b/domains/health/semaglutide-reduces-depression-worsening-44-percent-in-diagnosed-patients-through-glp1r-psychiatric-mechanism.md @@ -11,7 +11,7 @@ sourced_from: health/2026-05-03-lancet-psychiatry-swedish-glp1-mental-health-wor scope: causal sourcer: Lancet Psychiatry / Karolinska Institutet supports: ["glp1-receptor-agonists-address-substance-use-disorders-through-mesolimbic-dopamine-modulation"] -related: ["the-mental-health-supply-gap-is-widening-not-closing-because-demand-outpaces-workforce-growth", "social-isolation-costs-medicare-7-billion-annually-and-carries-mortality-risk-equivalent-to-smoking-15-cigarettes-per-day-making-loneliness-a-clinical-condition-not-a-personal-problem", "glp1-receptor-agonists-address-substance-use-disorders-through-mesolimbic-dopamine-modulation", "semaglutide-produces-large-effect-aud-reduction-through-vta-dopamine-suppression", "semaglutide-outperforms-tirzepatide-cardiovascular-outcomes-despite-inferior-weight-loss-suggesting-glp1r-specific-cardiac-mechanism", "real-world-semaglutide-shows-stronger-mace-reduction-than-select-trial", "glp1-receptor-agonists-demonstrate-superior-efficacy-for-alcohol-use-disorder-in-comorbid-obesity-population", "semaglutide-outperforms-tirzepatide-cardiovascular-outcomes-despite-inferior-weight-loss"] +related: ["the-mental-health-supply-gap-is-widening-not-closing-because-demand-outpaces-workforce-growth", "social-isolation-costs-medicare-7-billion-annually-and-carries-mortality-risk-equivalent-to-smoking-15-cigarettes-per-day-making-loneliness-a-clinical-condition-not-a-personal-problem", "glp1-receptor-agonists-address-substance-use-disorders-through-mesolimbic-dopamine-modulation", "semaglutide-produces-large-effect-aud-reduction-through-vta-dopamine-suppression", "semaglutide-outperforms-tirzepatide-cardiovascular-outcomes-despite-inferior-weight-loss-suggesting-glp1r-specific-cardiac-mechanism", "real-world-semaglutide-shows-stronger-mace-reduction-than-select-trial", "glp1-receptor-agonists-demonstrate-superior-efficacy-for-alcohol-use-disorder-in-comorbid-obesity-population", "semaglutide-outperforms-tirzepatide-cardiovascular-outcomes-despite-inferior-weight-loss", "semaglutide-reduces-depression-worsening-44-percent-in-diagnosed-patients-through-glp1r-psychiatric-mechanism", "glp1-psychiatric-effects-directionally-opposite-metabolic-versus-psychiatric-populations", "semaglutide-demonstrates-superior-aud-efficacy-to-all-approved-medications-in-comorbid-obesity-population"] --- # Semaglutide reduces depression worsening by 44 percent in patients with pre-existing depression through GLP-1R-mediated psychiatric protective effects @@ -24,3 +24,10 @@ A Swedish national cohort study of 95,490 adults with diagnosed depression, anxi **Source:** VigiBase study, Clinical Nutrition 2025 VigiBase disproportionality analysis shows semaglutide-specific signals for depressed mood (aROR 1.70), suicidality (aROR 1.45), and anxiety (aROR 1.26). Only semaglutide showed signals in BOTH FAERS and VigiBase for depression. Liraglutide and tirzepatide showed NO significant depressive disorder signals. This contradicts the Swedish cohort protective finding and suggests semaglutide may have drug-specific psychiatric risks not shared by other GLP-1 RAs. + + +## Extending Evidence + +**Source:** VigiBase semaglutide-specific analysis + +VigiBase data shows semaglutide additional psychiatric signals beyond eating disorders: depressed mood disorders (aROR 1.70), suicidality (aROR 1.45), anxiety (aROR 1.26). These signals are weaker than eating disorder signal (aROR 6.80) but suggest psychiatric effects are multi-dimensional, not uniformly protective. diff --git a/inbox/queue/2025-xx-vigibase-glp1-psychiatric-adverse-events-eating-disorders.md b/inbox/archive/health/2025-xx-vigibase-glp1-psychiatric-adverse-events-eating-disorders.md similarity index 97% rename from inbox/queue/2025-xx-vigibase-glp1-psychiatric-adverse-events-eating-disorders.md rename to inbox/archive/health/2025-xx-vigibase-glp1-psychiatric-adverse-events-eating-disorders.md index 169994eb0..57f955af7 100644 --- a/inbox/queue/2025-xx-vigibase-glp1-psychiatric-adverse-events-eating-disorders.md +++ b/inbox/archive/health/2025-xx-vigibase-glp1-psychiatric-adverse-events-eating-disorders.md @@ -7,10 +7,13 @@ date: 2025-01-01 domain: health secondary_domains: [] format: paper -status: unprocessed +status: processed +processed_by: vida +processed_date: 2026-05-04 priority: high tags: [glp1, pharmacovigilance, eating-disorders, vigibase, psychiatric-adverse-events, semaglutide, class-effect] intake_tier: research-task +extraction_model: "anthropic/claude-sonnet-4.5" --- ## Content