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What Causes What
MECHANISM0 NULL

GLP-1 receptor agonist → Depression

A rise in GLP-1 receptor agonist does not identify a change in Depression.

In 3,377 adults with overweight or obesity and no known major psychiatric illness, weekly semaglutide 2.4 mg did not raise PHQ-9 depression scores versus placebo (Wadden 2024). A later trial in major depression found no change in symptom severity.

Randomized trial · Contested · N=3377

Supported by an experiment or a tightly identified design. Read the caveats.

Mechanism

Weight loss can lift mood in people who were not depressed. A gut-hormone effect on reward circuits is also on the table. Spontaneous safety reports raised a suicide scare. The assigned trials count a PHQ-9 or a structured depression scale, not a database of tips. Wadden, Brown, Egebjerg and colleagues (2024) pooled STEP 1, 2, and 3 (68 weeks) and looked at STEP 5 (104 weeks). Adults with overweight or obesity; STEP 2 also had type 2 diabetes. People with recent severe depression were kept out. Baseline PHQ-9 was about 2, no or minimal symptoms. At week 68 the scores were 2.0 on semaglutide and 2.4 on placebo. Treatment difference -0.56 (95 percent CI -0.81 to -0.32). A shift to a worse PHQ-9 band was less common on drug (odds ratio 0.63). On the Columbia scale, 1 percent or fewer reported suicidal ideation or behaviour. full_text. Badulescu, Gill, Shah and colleagues (2026) assigned 72 adults with major depression, cognitive impairment, and overweight to oral semaglutide 14 mg or placebo for 16 weeks. Depression severity and suicidal ideation did not differ. Executive function, the primary end point, did not move. abstract_only.

Caveats

Someone was assigned a pen, so the stamp is an RCT stamp. The file is contested. STEP excluded people with recent major depression and started on a PHQ-9 floor of 2. A half-point gap is not an antidepressant claim. The 2026 depression trial is 72 people and 16 weeks. Symptom scores did not move. Did not hang FAERS or VigiBase reports (p-pmid-38087976, p-pmid-39433133): spontaneous tips, no assigned trial. Did not hang the antidepressant-at-baseline weight look, the Australian dispensing association, or the GRADE diabetes-distress file. This page is a journal entry. It is not medical advice and not a reason to start or stop a drug.

Effect

qualitative. STEP 1-3 PHQ-9 ETD -0.56 (CI -0.81 to -0.32) from a floor of ~2. N=3377, no known major psychopathology. Badulescu 2026 MDD: depression severity NS. N=72.

Nodes

Lifestyle & environmentGLP-1 receptor agonistPsychology & behaviorDepression

Named confounders

Cite this page

What Causes What. “GLP-1 receptor agonist → Depression.” https://whatcauseswhat.org/edges/e-glp1-depression (atlas updated 2026-09-02).

https://whatcauseswhat.org/edges/e-glp1-depression

Papers