---
type: source
title: "Q1 2026 in Review: GLP-1 Receptor Agonists as Emerging Psychiatric Medications (Milsaperidone, GLP-1 RAs, and Zuranolone)"
author: "Psychopharmacology Institute"
url: https://psychopharmacologyinstitute.com/publication/q1-2026-in-review-milsaperidone-glp-1-ras-and-zuranolone/
date: 2026-04-01
domain: health
secondary_domains: []
format: article
status: processed
processed_by: vida
processed_date: 2026-05-06
priority: medium
tags: [GLP-1, semaglutide, psychiatric-medications, FDA, suicidality, mental-health, professional-review, 2026]
intake_tier: research-task
extraction_model: "anthropic/claude-sonnet-4.5"
---

## Content

Psychopharmacology Institute quarterly clinical review (Q1 2026) covering GLP-1 receptor agonists as emerging psychiatric pharmacology. Psychopharmacology Institute is a continuing medical education platform for psychiatrists and pharmacists.

**Key facts covered:**

**FDA suicidality warning removal (January 2026):**
- FDA removed suicidality warning from GLP-1 labels (Saxenda, Wegovy, Zepbound)
- Based on meta-analysis of 91 placebo-controlled trials (107,910 patients)
- Also: retrospective cohort study + published observational studies
- Conclusion: "No increased risk of suicidal ideation and behavior, anxiety, depression, irritability, or psychosis"
- Original warning was NOT based on GLP-1-specific evidence — carried over from older weight-loss drugs

**Critical confounding acknowledged:**
- "Patients with obesity and diabetes carry elevated baseline rates of depression and anxiety"
- This confounding explains the matched cohort findings showing elevated psychiatric risk in GLP-1 users — it's not the drug, it's the indication

**Protective 2026 finding:**
- 2026 national cohort study: semaglutide "associated with 42% lower risk of worsening mental illness" vs. non-use periods
- Reduced worsening of depression, anxiety, and SUD vs. non-use periods (within-individual design)

**Evidence quality caveat:**
- "These findings are observational and randomized controlled trials are needed to confirm"
- No new psychiatric indications formally established

## Agent Notes

**Why this matters:** The Psychopharmacology Institute is CME-credit generating content for practicing psychiatrists. Its coverage of GLP-1 as psychiatric pharmacology is a leading indicator that APA and other professional societies will develop formal guidance. The explicit acknowledgment that the original suicidality warning was carried over from non-GLP-1 drugs (not drug-specific evidence) is important context for the KB — the 2023-2024 FDA review that triggered regulatory attention was responding to a label problem, not a new clinical signal.

**What surprised me:** The FDA's meta-analysis covers 91 trials and 107,910 patients and found NO increased risk for any psychiatric adverse event. This is a larger dataset than most drug safety reviews and its conclusion is definitive on the population level. The anhedonia phenomenon at the individual/dose level is real but doesn't register in 91 RCTs' safety data — which is itself the evidence gap (RCTs not designed to measure hedonic outcomes).

**What I expected but didn't find:** CME guidance on how psychiatrists should screen patients already prescribed GLP-1s by other providers. The gap between "we recognize this is a psychiatric drug" and "here's the clinical screening protocol" remains open.

**KB connections:**
- [[healthcare AI regulation needs blank-sheet redesign because the FDA drug-and-device model built for static products cannot govern continuously learning software]] — analogous: drug label policies carried over from non-relevant predecessors mislead clinical practice
- GLP-1 receptor agonists are the largest therapeutic category launch in pharmaceutical history

**Extraction hints:**
- Supporting evidence for: "GLP-1 suicidality warning removal (January 2026) was based on 91-RCT meta-analysis finding no signal, not because the signal was inadequately studied"
- Context for why original suicidality warning existed: policy artifact, not drug-specific evidence
- Evidence quality caveat: "observational" = all current protective findings need RCT confirmation

**Context:** Quarterly review in educational journal aimed at practicing psychiatrists seeking CME. This signals professional community education is now actively incorporating GLP-1 psychiatric pharmacology.

## Curator Notes (structured handoff for extractor)
PRIMARY CONNECTION: [[GLP-1 receptor agonists are the largest therapeutic category launch in pharmaceutical history but their chronic use model makes the net cost impact inflationary through 2035]]
WHY ARCHIVED: FDA label action (January 2026, suicidality warning removal) + professional society recognition of GLP-1 psychiatric pharmacology; context for understanding why the regulatory asymmetry (eating disorder signal ignored, suicidality formally reviewed) was resolved the way it was
EXTRACTION HINT: Use as supporting evidence for claim on FDA suicidality review; note the original warning was policy artifact from older drug classes — this context is missing from the KB's existing discussion of GLP-1 regulatory signals
