CHANGES IN SYMPTOMS OF SUICIDAL IDEATION AND RELATED SYMPTOMS WITH TIRZEPATIDE IN INDIVIDUALS WITH MODERATE-TO-SEVERE METHAMPHETAMINE USE DISORDER

Background

Glucagon-like peptide-1 (GLP-1) receptor agonists have gained recent attention for drug repurposing to treat substance use disorder. Yet, tirzepatide, a dual agonist of GLP-1/glucose-dependent insulinotropic polypeptide, has not been studied yet, especially for methamphetamine use disorder (MtUD). Furthermore, while these medications are gaining a lot of attention in clinical care, some concerns have been raised about their effect on suicide-related outcomes. Here, we present findings from the first study of a GLP-1 receptor agonist in individuals with MtUD where we systematically studied suicide-related outcomes with weekly self-report and clinician assessments.

Methods

This interim analysis included participants with moderate-to-severe MtUD who received six months of treatment with tirzepatide for a weight-related indication (NCT06745128). Self-reported symptoms of active suicidal ideation (SI), pessimism, helplessness, perceived lack of social support, despair, and impulsivity were assessed with Concise Health Risk Tracking Self-Report (CHRT-SR) measures on a weekly basis. Medical Clinicians also completed assessments of SI, suicidal behavior and non-suicidal self-injurious behavior every week. Repeated measures mixed model analyses were used to measures changes in CHRT-SR domains.

Results

Of the 42 individuals screened, 35 were enrolled [20 females/15 males; mean (standard deviation, SD) age = 46.1 (8.3) years]. Two individuals dropped out after the first dose due to gastrointestinal side effects. After six months of treatment with tirzepatide, there were significant reductions in pessimism [estimate(β)= -2.3, standard error(SE)= 0.25, p=0.0124], helplessness (β= -0.81, SE= 0.28, p=0.0035), perceived lack of social support (β= -0.70, SE= 0.28, p=0.0133), and impulsivity (β= -1.76, SE= 0.31, p < 0.0001), but not in despair (p=0.058) and active SI (p=0.56). No treatment-emergent worsening of SI or occurrence of suicidal behavior or non-suicidal self-injurious behaviors were noted over the six months treatment duration.

Conclusions

This first study of a GLP-1 receptor agonist in individuals with moderate-tosevere methamphetamine use disorder demonstrates significant reduction in symptoms associated with SI, such as impulsivity, pessimism and helplessness. Additionally, there was no signal for worsening of suicidal ideation or occurrence of behaviors with six-month-long treatment with tirzepatide.

References

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