vida: extract claims from 2026-05-03-vigibase-pharmacovigilance-glp1-psychiatric-signals

- Source: inbox/queue/2026-05-03-vigibase-pharmacovigilance-glp1-psychiatric-signals.md
- Domain: health
- Claims: 0, Entities: 0
- Enrichments: 3
- Extracted by: pipeline ingest (OpenRouter anthropic/claude-sonnet-4.5)

Pentagon-Agent: Vida <PIPELINE>

domains/health/glp1-psychiatric-effects-directionally-opposite-metabolic-versus-psychiatric-populations.md

@@ -16,3 +16,10 @@ related: ["clinical-ai-bias-amplification-creates-compounding-disparity-risk-at-
 # 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
 
 The GLP-1 psychiatric safety paradox resolves through population stratification rather than dismissing either signal. Clinical trials and cohort studies systematically exclude patients with 'psychiatric instability' — specifically those with substance use disorders, prior mood episodes, or active anhedonia. This creates a bifurcated evidence base: (1) Trial/cohort populations over-represent metabolically driven psychiatric patients where GLP-1 appears protective (Swedish cohort showing reduced depression/anxiety in metabolic disease context), and (2) Pharmacovigilance captures real-world deployment including psychiatric comorbidity patients where GLP-1 may worsen symptoms. The highest-risk subpopulation is patients on concurrent psychotropic medications (antidepressants, benzodiazepines) showing OR 4.07-4.45 for suicidality reporting. The Novo Nordisk semaglutide MDD program (interim data late 2026) will provide the first prospective RCT evidence in psychiatric patients rather than metabolic patients with psychiatric comorbidities, serving as the decisive test of whether GLP-1 is genuinely antidepressant or whether the metabolic patient finding is a selection effect. The eating disorder signal is consistent with this framework: GLP-1 appetite suppression may trigger pathology in vulnerable patients systematically excluded from trials but present in real-world deployment.
+
+
+## Supporting Evidence
+
+**Source:** VigiBase study, Clinical Nutrition 2025
+
+VigiBase disproportionality analysis confirms psychiatric adverse event signals are drug-specific: only semaglutide showed significant signals in BOTH FAERS and VigiBase for depression (FAERS ROR 1.26; VigiBase ROR 1.38), while liraglutide and tirzepatide showed NO significant depressive disorder signals. This supports the hypothesis that psychiatric effects vary by specific GLP-1 RA formulation, not just by patient population. Concurrent antidepressant use showed OR 4.45 for suicidal ideation reports, and concurrent benzodiazepines showed OR 4.07, indicating highest-risk patients are those with pre-existing psychiatric pharmacotherapy.

domains/health/glp1-receptor-agonists-demonstrate-superior-efficacy-for-alcohol-use-disorder-in-comorbid-obesity-population.md

@@ -12,9 +12,16 @@ scope: causal
 sourcer: NIH / JAMA Psychiatry
 supports: ["glp1-receptor-agonists-address-substance-use-disorders-through-mesolimbic-dopamine-modulation"]
 challenges: ["the mental health supply gap is widening not closing because demand outpaces workforce growth and technology primarily serves the already-served rather than expanding access"]
-related: ["glp1-receptor-agonists-address-substance-use-disorders-through-mesolimbic-dopamine-modulation", "semaglutide-produces-large-effect-aud-reduction-through-vta-dopamine-suppression"]
+related: ["glp1-receptor-agonists-address-substance-use-disorders-through-mesolimbic-dopamine-modulation", "semaglutide-produces-large-effect-aud-reduction-through-vta-dopamine-suppression", "glp1-receptor-agonists-demonstrate-superior-efficacy-for-alcohol-use-disorder-in-comorbid-obesity-population"]
 ---
 
 # GLP-1 receptor agonists demonstrate NNT 4.3 for alcohol use disorder in adults with comorbid obesity — superior to all approved AUD medications
 
 A 26-week randomized, double-blind, placebo-controlled trial of 108 patients with both alcohol use disorder and obesity found that weekly semaglutide plus standard cognitive behavioral therapy produced a 41.1% reduction in heavy drinking days, with 13.7% greater improvement than placebo. The number needed to treat (NNT) was 4.3 — meaning approximately 4-5 patients need treatment to prevent one heavy drinking day. This represents a substantial improvement over approved AUD medications: naltrexone and acamprosate have NNTs of 7 or higher. Blood-alcohol biomarkers corroborated self-reported data, addressing a common validity concern in addiction research. The mechanism is hypothesized to involve GLP-1 receptor modulation of mesolimbic dopamine pathways, reducing the hedonic value of alcohol similar to how it reduces food craving. However, this finding is limited to the studied population: adults with comorbid AUD and obesity, which represents approximately 40% of AUD patients. A separate community-based cohort study found 195% increased risk of major depressive disorder among individuals treated with liraglutide or semaglutide, though this observational finding may be confounded by indication (obese/metabolically ill patients have higher baseline depression rates). Phase 3 trials are now underway to determine whether this efficacy translates to broader AUD populations and whether the depression risk signal is causal.
+
+
+## Challenging Evidence
+
+**Source:** VigiBase study, Clinical Nutrition 2025
+
+VigiBase pharmacovigilance analysis shows semaglutide has significant disproportionate reporting for eating disorders (aROR 4.17-6.80 across all three GLP-1 RAs studied), suggesting GLP-1's appetite suppression mechanism may precipitate eating disorder pathology in vulnerable individuals. This is the highest-magnitude psychiatric safety signal, exceeding depression (aROR 1.70) and suicidality (aROR 1.45) signals. The eating disorder signal appears as a class effect across semaglutide, dulaglutide, and liraglutide, not drug-specific.

inbox/archive/health/2026-05-03-vigibase-pharmacovigilance-glp1-psychiatric-signals.md

@@ -7,10 +7,13 @@ date: 2025-12-01
 domain: health
 secondary_domains: []
 format: research-article
-status: unprocessed
+status: processed
+processed_by: vida
+processed_date: 2026-05-03
 priority: medium
 tags: [GLP-1, semaglutide, psychiatric-safety, pharmacovigilance, vigibase, adverse-events, depression, suicidality, eating-disorders]
 intake_tier: research-task
+extraction_model: "anthropic/claude-sonnet-4.5"
 ---
 
 ## Content