Does Ozempic (semaglutide) cause anxiety?

Does Ozempic Cause Anxiety?

Based on the available evidence, anxiety is a documented side effect of semaglutide (Ozempic), though it occurs relatively infrequently—reported in approximately 38.7% of psychiatric adverse event cases, which themselves represent only 1.2% of all adverse event reports. 1

Evidence for Anxiety as a Side Effect

Anxiety is explicitly listed among the documented side effects of GLP-1 receptor agonists, including semaglutide, in both clinical guidelines and FDA-approved drug information. 2 The American Gastroenterological Association recognizes anxiety as a potential adverse effect that warrants monitoring during treatment. 2

Pharmacovigilance Data

A comprehensive analysis of the EudraVigilance database (covering 31,444 adverse event reports for GLP-1 receptor agonists from January 2021 to May 2023) identified anxiety as the second most common psychiatric adverse event after depression, occurring in 144 cases (38.7% of psychiatric reports). 1 While psychiatric adverse events comprised only 1.2% of total reports, the presence of anxiety alongside other serious psychiatric symptoms (including depression and suicidal ideation) suggests this is a clinically relevant concern. 1

Clinical Context and Severity

The psychiatric adverse events associated with semaglutide can be serious—the same pharmacovigilance analysis documented 9 deaths and 11 life-threatening outcomes among psychiatric adverse event reports. 1 Women accounted for 65% of psychiatric adverse event reports, suggesting potential sex-based differences in susceptibility. 1

Mechanism and Timing

GLP-1 receptors are widely distributed throughout the central nervous system, including the hypothalamus, brainstem, hippocampus, neocortex, spinal cord, and cerebellum, providing a neuroanatomical basis for potential psychiatric effects. 3 This widespread CNS distribution may explain how semaglutide could influence mood and anxiety pathways beyond its metabolic effects.

Psychiatric symptoms, including anxiety, typically emerge approximately one month after initiating semaglutide treatment. 4, 5 This temporal relationship has been documented in multiple case reports where symptoms improved or resolved after discontinuation of the medication. 4, 5

Clinical Management Algorithm

1. Pre-Treatment Screening

• Screen all patients for personal or family history of psychiatric illness, including anxiety disorders, before initiating semaglutide 4
• Document baseline mental health status to enable detection of new-onset symptoms 4

2. Monitoring During Treatment

• Monitor for anxiety symptoms regularly, particularly during the first 1-2 months after initiation or dose escalation 2, 4
• Pay special attention to female patients, who appear to report psychiatric adverse events more frequently 1
• Watch for co-occurring symptoms such as restlessness, depressive mood, or sleep disturbances, which may indicate broader psychiatric effects 4

3. Management of Anxiety Symptoms

• If new-onset anxiety develops after starting semaglutide, consider discontinuation of the medication, as symptoms have been shown to improve after stopping treatment 4, 5
• Dose adjustment may be considered for mild symptoms, though evidence for this approach is limited 2
• If anxiety persists despite dose adjustment and significantly affects quality of life, alternative diabetes or weight-loss medications should be considered 2

Important Caveats

The overall incidence of psychiatric adverse events with semaglutide is low (1.2% of all adverse event reports), but the potential severity—including suicidal ideation in 19.6% of psychiatric cases—warrants vigilance. 1 The risk-benefit calculation should account for the substantial metabolic and cardiovascular benefits of semaglutide (38% higher risk of serious adverse events overall compared to placebo, but 26% reduction in cardiovascular death, MI, or stroke in appropriate populations). 3

Gradual dose titration may help mitigate side effects, including potential psychiatric symptoms, though this has been studied primarily for gastrointestinal effects. 2 The standard titration schedule (starting at 0.25 mg weekly and increasing every 4 weeks) should be followed to minimize adverse events. 3

Special Populations

Patients with pre-existing psychiatric conditions, including anxiety disorders, require particularly careful monitoring when initiating semaglutide. 4 While the medication is not contraindicated in these patients, the temporal relationship between drug initiation and symptom onset should be closely tracked. 4, 5

The absolute contraindications for semaglutide remain personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2—psychiatric history is not an absolute contraindication but requires enhanced monitoring. 3, 2