Study · Randomized controlled trial · n = 4,056 · 2026

5 results

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

Wadden TA, Oquendo MA, Kushner RF, Cao D, Karanikas CA, Kechter A, Murphy MA

Obesity (Silver Spring, Md.)15 Jan 2026Cited by 3 (Europe PMC)

PMID41537305PMCIDPMC12933222DOI10.1002/oby.70122PepBankPUB-41537305

Summary

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.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

5 results from studies that gave the peptide. 5 results from people.

01HumanRandomized controlled trialSafety outcome
In adults with obesity without known major psychopathology, PHQ-9 scores at week 72 were lower with tirzepatide than placebo (1.9 vs 2.4; estimated treatment difference -0.6).
In plain wordsIn adults with obesity and no known major mental illness, tirzepatide users had slightly lower depression questionnaire scores than placebo users.
Peptide
Tirzepatide
Outcome
DecreasePHQ-9 depressive symptom score at week 72
Study
n = 4,056
Comparator
Placebo
Outcome group
Anxiety and mood · Mental health and mood
Studied dose
5, 10 or 15 mg, or maximum tolerated dose 10/15 mg · 72 weeksAs given in this study (human).
Measurements
PHQ-9 score tirzepatide
1.9 points
week 72
PHQ-9 score placebo
2.4 points
week 72
Estimated treatment difference
−0.6 points
week 72
Source sentences
Summary
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.
1 context sentence(design, population, supporting numbers)
Summary · context
In 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.
Show in the study text Report a problemFND-4153730501
02HumanRandomized controlled trialSafety outcome
In adults with obesity without known major psychopathology, fewer tirzepatide-treated participants shifted to a more severe PHQ-9 category than with placebo (18.2% vs 24.3%).
In plain wordsIn adults with obesity and no known major mental illness, fewer people on tirzepatide moved to a worse depression category than on placebo.
Peptide
Tirzepatide
Outcome
DecreaseShift to a more severe PHQ-9 category
Study
n = 4,056
Comparator
Placebo
Outcome group
Anxiety and mood · Mental health and mood
Studied dose
5, 10 or 15 mg, or maximum tolerated dose 10/15 mg · 72 weeksAs given in this study (human).
Measurements
Shift to more severe category tirzepatide
18.2%
Shift to more severe category placebo
24.3%
Source sentences
Summary
Tirzepatide-treated participants were less likely to shift to a more severe PHQ-9 category (18.2% vs. 24.3%; p < 0.001).
1 context sentence(design, population, supporting numbers)
Summary · context
In 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.
Show in the study text Report a problemFND-4153730502
03HumanRandomized controlled trialSafety outcome
In adults with obesity without known major psychopathology, suicidal ideation was reported by 0.6% of participants in each group.
In plain wordsIn adults with obesity and no known major mental illness, suicidal thoughts were reported by 0.6% of people in both the tirzepatide and placebo groups.
Peptide
Tirzepatide
Outcome
No significant changeSuicidal ideation (C-SSRS)
Study
n = 4,056
Comparator
Placebo
Outcome group
Anxiety and mood · Mental health and mood
Studied dose
5, 10 or 15 mg, or maximum tolerated dose 10/15 mg · 72 weeksAs given in this study (human).
Measurements
Suicidal ideation, each group
0.6%
Source sentences
Summary
0.6% of participants in each group reported SI
1 context sentence(design, population, supporting numbers)
Summary · context
In 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.
Show in the study text Report a problemFND-4153730503
04HumanRandomized controlled trialSafety outcome
In adults with obesity without known major psychopathology, nonfatal suicidal behavior occurred in 0.1% of tirzepatide-treated participants versus none with placebo; no significance test is reported.
In plain wordsIn adults with obesity and no known major mental illness, 0.1% on tirzepatide and none on placebo had nonfatal suicidal behavior; numbers are very small.
Peptide
Tirzepatide
Outcome
IncreaseSuicidal behavior (nonfatal)
Study
n = 4,056
Comparator
Placebo
Outcome group
Anxiety and mood · Mental health and mood
Studied dose
5, 10 or 15 mg, or maximum tolerated dose 10/15 mg · 72 weeksAs given in this study (human).
Measurements
Suicidal behavior tirzepatide
0.1%
Source sentences
Summary
SB (nonfatal) occurred in 0.1% of tirzepatide-treated participants versus none with placebo.
1 context sentence(design, population, supporting numbers)
Summary · context
In 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.
Show in the study text Report a problemFND-4153730504
05HumanRandomized controlled trialSafety outcome
In adults with obesity without known major psychopathology, adverse events were generally similar across the tirzepatide and placebo groups.
In plain wordsIn adults with obesity and no known major mental illness, side effects were generally similar for tirzepatide and placebo.
Peptide
Tirzepatide
Outcome
No significant changeNervous system and psychiatric adverse events
Study
n = 4,056
Comparator
Placebo
Outcome group
Adverse events · Mental health and mood
Studied dose
5, 10 or 15 mg, or maximum tolerated dose 10/15 mg · 72 weeksAs given in this study (human).
Source sentences
Summary
AEs were generally similar across groups.
1 context sentence(design, population, supporting numbers)
Summary · context
In 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.
Show in the study text Report a problemFND-4153730505

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials3

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

3 trials · 3 completed · 3 with posted results · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 3Results postedNCT04657003

A Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes Who Have Obesity or Are Overweight

Eli Lilly and Companyn = 93829 Mar 2021 to 10 Apr 2023

Type 2 Diabetes · Overweight · Obesity

Trial page ClinicalTrials.govUpdated 8 Apr 2024

CompletedPhase 3Results postedNCT04657016

A Study of Tirzepatide (LY3298176) In Participants After A Lifestyle Weight Loss Program

Eli Lilly and Companyn = 57929 Mar 2021 to 12 May 2023

Obesity · Overweight

Trial page ClinicalTrials.govUpdated 16 May 2024

CompletedPhase 3Results postedNCT04184622

A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight

Eli Lilly and Companyn = 2,5394 Dec 2019 to 6 Jul 2024

Overweight · Obesity

Trial page ClinicalTrials.govUpdated 24 Jul 2025

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
12 Oct 2026, 12:10 UTC
Study results updated
Version 1
9 Oct 2026, 03:07 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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