SURMOUNT post hoc analysis finds no increase in depression risk on tirzepatide

A post hoc analysis of three large obesity trials found no sign that tirzepatide raises the risk of depression, according to a study published January 15, 2026, in the journal Obesity ^[1]. Tirzepatide is sold under the brand names Mounjaro and Zepbound.

The analysis pooled data from 4,056 participants across SURMOUNT-1, SURMOUNT-2, and SURMOUNT-3, three randomized trials comparing tirzepatide to placebo in adults with obesity or overweight ^[1]. Researchers tracked mood using the Patient Health Questionnaire-9 (PHQ-9), a standard nine-item depression screening tool, and suicidal thoughts and behavior using the Columbia-Suicide Severity Rating Scale (C-SSRS) ^[1].

At the start of the trials, average PHQ-9 scores were nearly identical between groups: 2.7 for tirzepatide and 2.6 for placebo, both indicating no or minimal depression symptoms ^[1]. By week 72, scores had dropped to 1.9 in the tirzepatide group and 2.4 in the placebo group, a statistically significant difference ^[1]. Participants on tirzepatide were also less likely to slide into a more severe depression category over the course of the trial, 18.2% versus 24.3% on placebo ^[1].

Suicidal ideation was reported at the same rate in both groups, 0.6% ^[1]. Most of those reports were classified as low risk ^[1]. Nonfatal suicidal behavior was reported in 0.1% of tirzepatide-treated participants and in no one on placebo, a difference the authors describe as two people out of thousands ^[1]. Overall rates of adverse events tied to nervous system or psychiatric disorders were generally similar between the two groups ^[1].

An important limitation shapes how far these findings can be applied: participants with known major psychiatric illness were excluded from the original trials ^[1]. The authors write that further study of tirzepatide's safety in people with significant psychiatric illness may be warranted, since this analysis cannot speak to that population ^[1].

Why it matters for patients

Concerns about GLP-1 drugs and mood have circulated since regulators and clinicians began flagging the need to monitor patients for signs of depression or suicidal thinking ^[1]. In January 2024, the FDA reviewed clinical trial and pharmacovigilance data for GLP-1 receptor agonists used for obesity or type 2 diabetes and concluded it had not found evidence that these medications cause suicidal thoughts or actions ^[1].

This new analysis adds trial-level evidence consistent with that conclusion for tirzepatide specifically, at least in people without a history of major psychiatric illness ^[1]. The authors note that obesity itself is linked to a higher risk of depression, particularly at higher body mass index levels, tied to factors like weight stigma and chronic inflammation ^[1]. That context matters because any mood changes during weight-loss treatment can be hard to separate from the psychological effects of obesity itself, or from mood improvements that sometimes accompany weight loss.

For people already taking tirzepatide, or considering it, the data offer some reassurance that depression symptoms did not worsen more on the drug than on placebo in these trials. But the exclusion of people with major psychiatric illness means the findings don't address that group directly, and the study's authors themselves call for more research there ^[1]. The authors also continue to support existing recommendations that clinicians monitor mood and behavior in patients on incretin-based weight management drugs, alongside ongoing safety monitoring after the drugs reach the market ^[1].

What happens next

The study's authors call for continued post-marketing surveillance of tirzepatide's psychiatric safety and for further research specifically in people with significant psychiatric illness, a population not studied in SURMOUNT-1, -2, and -3 ^[1]. No specific timeline for that additional research is given in the source material.