Evidence mapPaperPMID 41537305Full record

Trial reportObesity (Silver Spring, Md.)2026

Psychiatric Safety of Tirzepatide in People With Obesity and No Known Major Psychopathology: A Post Hoc Analysis of SURMOUNT.

Thomas A Wadden, Maria A Oquendo, Robert F Kushner, Dachuang Cao, Chrisanthi A Karanikas, Afton Kechter, Madhumita A Murphy

3 registry-linked trialsAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Obesity (Silver Spring, Md.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT04184622. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04184622 phase3completed

Efficacy and Safety of Tirzepatide Once Weekly in Participants Without Type 2 Diabetes Who Have Obesity or Are Overweight With Weight- Related Comorbidities: A Randomized, Double-Blind, Placebo-Controlled Trial (SURMOUNT-1)

Ran2019Enrolled2,539Registered outcomes26Posted comparisons49ConditionsObesity, OverweightArmsPlacebo, Tirzepatide
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NCT04657003 phase3completed

Efficacy and Safety of Tirzepatide Once Weekly in Participants With Type 2 Diabetes Who Have Obesity or Are Overweight: A Randomized, Double-Blind, Placebo-Controlled Trial (SURMOUNT-2)

Ran2021Enrolled938Registered outcomes26Posted comparisons41ConditionsObesity, Overweight, Type 2 DiabetesArmsPlacebo, Tirzepatide
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NCT04657016 phase3completed

Efficacy and Safety of Tirzepatide Once Weekly Versus Placebo After an Intensive Lifestyle Program in Participants Without Type 2 Diabetes Who Have Obesity or Are Overweight With Weight-Related Comorbidities: A Randomized, Double Blind, Placebo-Controlled Trial (SURMOUNT-3)

Ran2021Enrolled579Registered outcomes22Posted comparisons22ConditionsObesity, OverweightArmsPlacebo, Tirzepatide
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3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Thomas A WaddenDepartment of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.ORCID https://orcid.org/0000-0002-0438-4609
Maria A OquendoDepartment of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.ORCID https://orcid.org/0000-0002-7901-5082
Robert F KushnerDivision of Endocrinology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.ORCID https://orcid.org/0000-0002-1380-3705
Dachuang CaoEli Lilly and Company, Indianapolis, Indiana, USA.ORCID https://orcid.org/0000-0003-2291-9037
Chrisanthi A KaranikasEli Lilly and Company, Indianapolis, Indiana, USA.ORCID https://orcid.org/0009-0008-0614-8264
Afton KechterEli Lilly and Company, Indianapolis, Indiana, USA.ORCID https://orcid.org/0000-0002-1228-742X
Madhumita A MurphyEli Lilly and Company, Indianapolis, Indiana, USA.

Funding

Eli Lilly and Company
6 · The paper itself

Abstract

objectiveThis post hoc analysis assessed psychiatric changes with tirzepatide in adults with obesity, without known major psychopathology, from SURMOUNT-1, SURMOUNT-2, and SURMOUNT-3.

methodsIn participants (N = 4056) treated with tirzepatide (5/10/15 mg or maximum tolerated dose 10/15 mg) versus placebo, depressive symptoms and suicidal ideation and behavior (SI/SB) were measured using the Patient Health Questionnaire-9 (PHQ-9) and Columbia-Suicide Severity Rating Scale (C-SSRS), respectively. Nervous system and psychiatric disorder adverse events (AEs) were collected.

resultsMean (SD) baseline PHQ-9 scores were 2.7 (3.0) for tirzepatide and 2.6 (3.1) for placebo, indicating no/minimal symptoms of depression. At week 72, scores were 1.9 (2.7) and 2.4 (3.3), respectively (estimated treatment difference [SE]: -0.6 [0.1]); p < 0.001. Tirzepatide-treated participants were less likely to shift to a more severe PHQ-9 category (18.2% vs. 24.3%; p < 0.001). Using the C-SSRS, 0.6% of participants in each group reported SI, most of which was considered low risk. SB (nonfatal) occurred in 0.1% of tirzepatide-treated participants versus none with placebo. AEs were generally similar across groups.

conclusionsIn this post hoc analysis, tirzepatide versus placebo did not appear to be associated with an increased risk of depression in participants with overweight/obesity and without known major psychopathology. Rates of SI/SB observed with tirzepatide were similar to those of other incretin-based therapies. Further study of tirzepatide's safety in persons with significant psychiatric illness may be warranted.

trial registrationClinicalTrials.gov identifiers: NCT04184622, NCT04657003, and NCT04657016.

Indexed as

Anti-Obesity AgentsDepressionObesityAdultDouble-Blind MethodFemaleHumansMaleMiddle AgedSuicidal IdeationTirzepatideAnti-Obesity AgentsTirzepatideclinical trialsC‐SSRSobesityPHQ‐9psychiatric safetytirzepatide

Identifiers

PMID41537305
PMCPMC12933222

What Socratic holds

Texttitle and abstract
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.