Can Ozempic Cause Low Mood?
Ozempic (semaglutide) is not established as a common cause of low mood in FDA labeling or major clinical guidelines, but emerging case reports and pharmacovigilance data suggest a potential psychiatric risk that warrants clinical vigilance, particularly for depression, anxiety, and suicidal ideation. 1, 2, 3, 4
Established Side Effect Profile from FDA and Guidelines
The FDA-approved labeling for Ozempic lists specific mood-related symptoms only in the context of hypoglycemia, including "anxiety, irritability, or mood changes" as signs of low blood sugar rather than direct psychiatric effects of the medication itself. 1
The most common adverse effects documented in clinical trials are gastrointestinal (nausea, vomiting, diarrhea, constipation, abdominal pain), occurring in the majority of patients but typically being transient and dose-dependent. 5, 1
Serious adverse events in trials showed a 38% higher risk with semaglutide versus placebo, but these primarily included pancreatitis, gallbladder disease, acute myocardial infarction, and gastroenteritis—not psychiatric conditions. 5
The American College of Cardiology and other guideline societies note injection site reactions and insomnia as potential side effects, but depression is not listed among established adverse reactions in major clinical guidelines. 5
Emerging Evidence of Psychiatric Adverse Events
Recent case reports and pharmacovigilance data reveal a concerning signal for mood disturbances that contradicts the absence of psychiatric warnings in official labeling:
Two published case reports document semaglutide-associated depression developing approximately 1 month after treatment initiation, with symptom improvement or resolution after discontinuation—one in a patient with no psychiatric history and another in a patient with recurrent depression whose symptoms relapsed. 2
A case report from 2025 describes a man in his late 70s with no psychiatric history who developed depressive symptoms, restlessness, and made his first suicide attempt (ingesting brush cleaner) one month after starting semaglutide, with psychiatric symptoms improving after drug discontinuation. 3
Analysis of the EudraVigilance database (January 2021 to May 2023) identified 372 psychiatric adverse event reports (1.18% of 31,444 total reports) for semaglutide, liraglutide, and tirzepatide combined, with depression being the most common (50.3%), followed by anxiety (38.7%) and suicidal ideation (19.6%). 4
This pharmacovigilance analysis documented 9 deaths (primarily men completing suicide) and 11 life-threatening outcomes, with women accounting for 65% of psychiatric adverse event reports. 4
Contradictory Evidence on Mental Health Effects
Importantly, some research suggests semaglutide may actually improve certain psychological symptoms:
A 2022 study of 69 people with obesity found that after 3 months of semaglutide, there was significant reduction in emotional eating (72.5% to 11.5%), external eating (27.5% to 10.1%), and cravings (49.3% to 21.7%), suggesting potential benefits for eating-related psychological distress. 6
Social media analysis across Reddit, YouTube, and TikTok revealed mixed reports, with weight loss from GLP-1 receptor agonists associated with either marked improvement or deterioration in mood, and variable effects on anxiety and insomnia. 7
The same social media analysis found reports of better control of addictive behaviors in some users, complicating the psychiatric risk profile. 7
Clinical Implications and Monitoring Recommendations
Given the severity of reported outcomes despite low overall incidence, a cautious approach is warranted:
Screen for personal or family history of depression, anxiety disorders, or suicidal ideation before initiating semaglutide, as patients with recurrent depression may be at higher risk for symptom recurrence. 2
Monitor specifically for new-onset depressive symptoms, anxiety, restlessness, or suicidal thoughts, particularly during the first 1-2 months after initiation or dose escalation, as this appears to be the highest-risk period. 2, 3
Educate patients and caregivers to report any mood changes, unusual restlessness, or thoughts of self-harm immediately, emphasizing that these are not typical side effects but require urgent evaluation. 3, 4
Consider discontinuation of semaglutide if new psychiatric symptoms emerge, as both case reports demonstrated symptom improvement after stopping the medication. 2, 3
The European Medicines Agency has initiated investigation into GLP-1 receptor agonists based on these psychiatric concerns, indicating regulatory awareness of this potential risk. 4
Important Caveats
The relationship between metabolic disease, obesity, depression, and medications is complex with possible reciprocal relationships and shared underlying mechanisms, making definitive cause-and-effect difficult to establish. 7
Depression and anxiety are already highly prevalent in people with obesity and type 2 diabetes, independent of medication use, which complicates attribution of psychiatric symptoms to semaglutide specifically. 7
The pharmacovigilance data represents only 1.2% of total adverse event reports, suggesting psychiatric effects are uncommon, but the severity of outcomes (including completed suicides) makes even rare events clinically significant. 4
Individual differences in response mean some patients may experience mood improvement (particularly related to weight loss success and reduced emotional eating), while others may develop new psychiatric symptoms. 6, 7