Exploring the association between suicidal thoughts, self-injury, and GLP-1 receptor agonists in weight loss treatments: Insights from pharmacovigilance measures and unmasking analysis

Mar 20, 2024European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology

Links between suicidal thoughts, self-injury, and weight loss drugs acting on GLP-1 receptors based on safety reports

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Abstract

A total of 5,378 psychiatric disorder cases were reported among 209,354 adverse drug reports from 2005-2023.

Among the psychiatric cases, 383 were classified as serious.
Liraglutide and semaglutide showed higher reported odds ratios for psychiatric disorders compared to other GLP-1 receptor agonists.
Metformin was associated with a greater frequency of adverse drug reactions related to psychiatric disorders than orlistat.
There were 42 deaths recorded, including 13 completed suicides, associated with the use of GLP-1 receptor agonists.
Suicidal ideation was recorded in 236 cases across 6 out of 7 GLP-1 receptor agonists examined.
No causal link between suicidal ideation and GLP-1 receptor agonists was established in the current analysis.

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INTRODUCTION: The study addresses concerns about potential psychiatric side effects of Glucagon-like peptide-1 receptor agonists (GLP-1 RA).

AIM: The aim of this work was to analyse adverse drug reports (ADRs) from the Food and Drug Administration Adverse Events Reporting System (FAERS) using metformin and orlistat as comparators.

METHODS: Descriptive and pharmacovigilance disproportionality analyses was performed.

RESULTS: A total of 209,354 ADRs were reported, including 59,300 serious cases. Of those, a total of 5378 psychiatric disorder cases, including 383 'serious' cases related to selected ADRs were registered during 2005-2023. After unmasking, 271 cases where individual GLP-1 RA were implicated showing liraglutide (n = 90; Reported Odds Ratio (ROR) = 1.64), exenatide (n = 67; ROR = 0.80), semaglutide (n = 61; ROR = 2.03), dulaglutide (n = 45; ROR = 0.84), tirzepatide (n = 5; ROR = 1.76) and albiglutide (n = 2; ROR = 0.04). A greater association between these ADRs with metformin was observed, but not orlistat. With regards to selected preferred terms (PTs), 42 deaths including 13 completed suicides were recorded. Suicidal ideation was recorded in n = 236 cases for 6/7 GLP-1 RA (excluding lixisenatide).

DISCUSSION: Suicide/self-injury reports pertaining to semaglutide; tirzepatide; and liraglutide were characterised, although lower than metformin. It is postulated that rapid weight loss achieved with GLP-1 RA can trigger significant emotional, biological, and psychological responses, hence possibly impacting on suicidal and self-injurious ideations.

CONCLUSIONS: With the current pharmacovigilance approach, no causality link between suicidal ideation and use of any GLP-1 RA can be inferred. There is a need for further research and vigilance in GLP-1 RA prescribing, particularly in patients with co-existing psychiatric disorders.

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Exploring the association between suicidal thoughts, self-injury, and GLP-1 receptor agonists in weight loss treatments: Insights from pharmacovigilance measures and unmasking analysis

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