vida: extract claims from 2026-05-02-glp1-psychiatric-safety-signal-195pct-mdd-risk-cohort

- Source: inbox/queue/2026-05-02-glp1-psychiatric-safety-signal-195pct-mdd-risk-cohort.md
- Domain: health
- Claims: 0, Entities: 0
- Enrichments: 4
- Extracted by: pipeline ingest (OpenRouter anthropic/claude-sonnet-4.5)

Pentagon-Agent: Vida <PIPELINE>

domains/health/glp1-prescribing-competency-gap-creates-structural-safety-risk-through-primary-care-psychiatric-drug-misclassification.md

@@ -10,22 +10,9 @@ agent: vida
 sourced_from: health/2026-05-07-osmind-glp1-psychiatric-drugs-competency.md
 scope: structural
 sourcer: Osmind
-related:
+related: ["human-in-the-loop-clinical-ai-degrades-to-worse-than-ai-alone", "value-based-care-transitions-stall-at-the-payment-boundary", "glp1-prescribing-competency-gap-primary-care-psychiatric-monitoring", "glp1-anhedonia-tonic-receptor-occupancy-dose-dependent-reversible", "behavioral-biological-health-dichotomy-false-for-reward-dysregulation-conditions", "glp1-psychiatric-dose-response-data-absent-despite-mechanistic-evidence", "glp1-psychiatric-effects-directionally-opposite-metabolic-versus-psychiatric-populations", "glp1-discontinuation-predicted-by-psychiatric-comorbidity-creating-access-adherence-trap", "glp1-atypical-anorexia-screening-gap-creates-invisible-high-risk-population", "glp1-prescribing-competency-gap-creates-structural-safety-risk-through-primary-care-psychiatric-drug-misclassification", "psychiatry-addresses-glp1-competency-through-cme-not-formal-guidelines-creating-uneven-distribution"]
-- human-in-the-loop-clinical-ai-degrades-to-worse-than-ai-alone
+supports: ["GLP-1 psychotropic co-medication quadruples suicidal ideation risk through pharmacodynamic interaction", "Psychiatry addresses GLP-1 prescribing competency through CME infrastructure rather than formal APA guidelines, creating uneven competency distribution across the prescriber population"]
-- value-based-care-transitions-stall-at-the-payment-boundary
+reweave_edges: ["GLP-1 psychotropic co-medication quadruples suicidal ideation risk through pharmacodynamic interaction|supports|2026-05-08", "Psychiatry addresses GLP-1 prescribing competency through CME infrastructure rather than formal APA guidelines, creating uneven competency distribution across the prescriber population|supports|2026-05-08"]
-- glp1-prescribing-competency-gap-primary-care-psychiatric-monitoring
-- glp1-anhedonia-tonic-receptor-occupancy-dose-dependent-reversible
-- behavioral-biological-health-dichotomy-false-for-reward-dysregulation-conditions
-- glp1-psychiatric-dose-response-data-absent-despite-mechanistic-evidence
-- glp1-psychiatric-effects-directionally-opposite-metabolic-versus-psychiatric-populations
-- glp1-discontinuation-predicted-by-psychiatric-comorbidity-creating-access-adherence-trap
-- glp1-atypical-anorexia-screening-gap-creates-invisible-high-risk-population
-supports:
-- GLP-1 psychotropic co-medication quadruples suicidal ideation risk through pharmacodynamic interaction
-- Psychiatry addresses GLP-1 prescribing competency through CME infrastructure rather than formal APA guidelines, creating uneven competency distribution across the prescriber population
-reweave_edges:
-- GLP-1 psychotropic co-medication quadruples suicidal ideation risk through pharmacodynamic interaction|supports|2026-05-08
-- Psychiatry addresses GLP-1 prescribing competency through CME infrastructure rather than formal APA guidelines, creating uneven competency distribution across the prescriber population|supports|2026-05-08
 ---
 
 # GLP-1 prescribing competency gap creates structural safety risk through primary care psychiatric drug misclassification
@@ -38,3 +25,9 @@ GLP-1 receptor agonists engage VTA, nucleus accumbens, insula, and prefrontal co
 **Source:** Psychopharmacology Institute Q1 2026 Review
 
 Psychopharmacology Institute Q1 2026 guidance establishes monthly monitoring using validated depression/suicidality tools and psychoeducation for mood lability, appetite changes, and suicidal ideation as the psychiatric-specific monitoring protocol. This protocol is disseminated through CME to psychiatrists but not systematically available to primary care prescribers.
+
+## Extending Evidence
+
+**Source:** PMC systematic review + JAMA Psychiatry RCT
+
+The 195% MDD risk signal from community-based cohort study (observational, confounded by indication) combined with AUD efficacy data (RCT, NNT 4.3) demonstrates that GLP-1 has complex psychiatric pharmacology requiring competency beyond metabolic prescribing. One mechanistic hypothesis: GLP-1 reduces reward salience (beneficial for addiction/cravings) but may reduce hedonic response broadly (potential depression pathway). This suggests behavioral health deployment requires psychiatric evaluation protocols, not just metabolic monitoring.

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

@@ -45,3 +45,10 @@ First RCT evidence that therapeutic doses in MDD population reduce motivation de
 **Source:** Sa et al. (2026)
 
 Meta-analyses show 'modest antidepressant effects, greater in type 2 diabetes populations' while observational data in obesity populations show '195% increased depression risk and 106% increased suicidal behavior risk.' This confirms directionally opposite effects by population, though confounding by indication complicates interpretation.
+
+
+## Supporting Evidence
+
+**Source:** PMC systematic review + JAMA Psychiatry RCT
+
+AUD RCT (N=108) showed 41.1% reduction in heavy drinking days with no psychiatric adverse events in comorbid AUD + obesity population. However, community-based cohort study of general GLP-1 prescription recipients found 195% increased MDD risk. This supports the claim that GLP-1 psychiatric effects differ by population: beneficial in addiction/metabolic comorbidity, potentially harmful in general metabolic-only populations. The literature is internally inconsistent, with systematic reviews finding both 'promising results for depression' and the 195% MDD risk signal.

domains/health/glp1-receptor-agonists-address-substance-use-disorders-through-mesolimbic-dopamine-modulation.md

@@ -164,3 +164,10 @@ Psychopharmacology Institute Q1 2026 guidance omits substance use disorder appli
 **Source:** Washington Post 2026-04-16, researcher interviews
 
 Contradictory animal evidence on dopamine mechanism: one lab found 'chronically muted dopamine responses' while another found 'turbocharged' dopamine signal. Some persistent anhedonia cases treated with bupropion (dopamine-enhancing antidepressant) as compensatory treatment, supporting dopaminergic pathway but revealing mechanistic uncertainty.
+
+
+## Supporting Evidence
+
+**Source:** JAMA Psychiatry RCT + PMC systematic review
+
+Semaglutide + CBT for AUD achieved 41.1% reduction in heavy drinking days with NNT 4.3 (vs. 7+ for approved AUD medications) in double-blind RCT (N=108). Mechanistic hypothesis: GLP-1 reduces reward salience through mesolimbic dopamine modulation, beneficial for addiction/cravings. However, this same mechanism may reduce hedonic response broadly, potentially explaining the 195% MDD risk signal in observational cohort data.

domains/health/semaglutide-demonstrates-superior-aud-efficacy-to-all-approved-medications-in-comorbid-obesity-population.md

@@ -32,3 +32,10 @@ Osmind states GLP-1s for AUD show 'effect sizes exceeding those historically see
 **Source:** Psychiatric News (APA), February 2026
 
 APA's Psychiatric News cites the 41.1% reduction in heavy drinking days (NNT 4.3) from JAMA Psychiatry 2025 as key efficacy data, but recommends GLP-1 RAs only as second-line treatment for patients with comorbid metabolic disease who are non-responsive to standard treatments. This creates evidence-to-guideline lag where superior NNT doesn't translate to first-line recommendation.
+
+
+## Challenging Evidence
+
+**Source:** PMC systematic review + JAMA Psychiatry RCT
+
+Large community-based cohort study found 195% increased risk of major depressive disorder among individuals treated with liraglutide or semaglutide. While the AUD RCT (N=108) showed 41.1% reduction in heavy drinking days with NNT 4.3 and no psychiatric adverse events, the observational cohort data suggests psychiatric monitoring infrastructure is required for behavioral health deployment. The mechanistic hypothesis is that GLP-1 reduces reward salience (beneficial for addiction) but may reduce hedonic response broadly (potential depression pathway). This creates a clinical tension: the drug is extraordinarily effective for AUD but may carry psychiatric risk requiring screening and monitoring protocols.

inbox/archive/health/2026-05-02-glp1-psychiatric-safety-signal-195pct-mdd-risk-cohort.md

@@ -7,10 +7,13 @@ date: 2026-01-01
 domain: health
 secondary_domains: []
 format: research-summary
-status: unprocessed
+status: processed
+processed_by: vida
+processed_date: 2026-05-08
 priority: high
 tags: [GLP-1, semaglutide, depression, MDD, psychiatric-safety, alcohol-use-disorder, behavioral-health, safety-signal]
 intake_tier: research-task
+extraction_model: "anthropic/claude-sonnet-4.5"
 ---
 
 ## Content