GLP-1 Receptor Agonists and Related Mental Health Issues; Insights from a Range of Social Media Platforms Using a Mixed-Methods Approach

Abstract

The emergence of glucagon-like peptide-1 receptor agonists (GLP-1 RAs; semaglutide and others) now promises effective, non-invasive treatment of obesity for individuals with and without diabetes. Social media platforms’ users started promoting semaglutide/Ozempic as a weight-loss treatment, and the associated increase in demand has contributed to an ongoing worldwide shortage of the drug associated with levels of non-prescribed semaglutide intake. Furthermore, recent reports emphasized some GLP-1 RA-associated risks of triggering depression and suicidal thoughts. Consistent with the above, we aimed to assess the possible impact of GLP-1 RAs on mental health as being perceived and discussed in popular open platforms with the help of a mixed-methods approach. Reddit posts yielded 12,136 comments, YouTube videos 14,515, and TikTok videos 17,059, respectively. Out of these posts/entries, most represented matches related to sleep-related issues, including insomnia (n = 620 matches); anxiety (n = 353); depression (n = 204); and mental health issues in general (n = 165). After the initiation of GLP-1 RAs, losing weight was associated with either a marked improvement or, in some cases, a deterioration, in mood; increase/decrease in anxiety/insomnia; and better control of a range of addictive behaviors. The challenges of accessing these medications were a hot topic as well. To the best of our knowledge, this is the first study documenting if and how GLP-1 RAs are perceived as affecting mood, mental health, and behaviors. Establishing a clear cause-and-effect link between metabolic diseases, depression and medications is difficult because of their possible reciprocal relationship, shared underlying mechanisms and individual differences. Further research is needed to better understand the safety profile of these molecules and their putative impact on behavioral and non-behavioral addictions.

Semaglutide as a Possible Calmodulin Binder: Ligand-Based Computational Analyses and Relevance to Its Associated Reward and Appetitive Behaviour Actions

“…Consistent with this, responses to cues predicting food rewards in VTA DA axons and basal amygdala neurons in hungry mice were strongly attenuated following satiation [46]. Sem-related decreased levels of food cravings reported by subjects prescribed with this molecule have been associated with earlier attainment, in Sem-related subjects, of food satiety [47,48]. This may occur because GLP-1 mimetics show pro-dopaminergic efficacy [49], and as a result can modulate reward [50].…”

“…This behaviour of misuse may arguably be occurring in both obese (e.g., through forged and/or diverted prescriptions) and healthy, non-obese individuals due to unrealistic ideals of physical attractiveness [51]. Although intake of Sem has not been associated with a stimulant-like 'high', a rebound syndrome may occur after abrupt Sem cessation [47].…”

Impact of treatment with GLP‐1RAs on suicide attempts in adults persons with type 2 diabetes: A retrospective comparative effectiveness study based on a global TriNetX health research database

“…Studies have reported a range of experiences from people using GLP-1RAs, including both positive effects on mood and negative experiences such as heightened anxiety and difficulty sleeping. 8 Real-world pharmacovigilance analysis has not shown a disproportionate increase in suicide/self-injury events overall associated with GLP-1RAs, but nuances exist, with a reported increase in children (OR: 2.50, 95%CI 1.02-6.13, p = .05). 6 Moreover, post hoc pooled data analysis from randomized controlled trials of liraglutide, a GLP-1RA, showed similarly low rates of depression and anxiety between the liraglutide and placebo groups but did reveal a small numerical imbalance in suicidal ideation among liraglutide users.…”

Exploring the Potential Impact of GLP-1 Receptor Agonists on Substance Use, Compulsive Behavior, and Libido: Insights from Social Media Using a Mixed-Methods Approach

“…Understanding the impact of GLP-1 RAs on mental health outcomes is complex, due to both the subjects’ individual differences and potential biases in data analysis [ 20 , 21 , 22 ]. Moreover, both obesity and type 2 diabetes are multifactorial and complex diseases, and their exact inter-relationship with mental health and addiction are not fully understood, including the psychopathological issues linked to food-related emotional and behavioral aspects [ 1 , 21 ]. Other unclear aspects may involve the interconnection between GLP-1 receptors and a range of cognitive-, immunological-, and inflammation-related issues [ 23 , 24 , 25 ].…”

“…These methods, initially used mainly in marketing and social sciences, have recently attracted increasing levels of interest in the scientific community, given both the obvious difficulties/limitations in carrying out clinical trials and the partial inadequacy of data that can be collected in clinics. Hence, “netnography”, when combined with content analysis and qualitative and quantitative analysis [ 21 , 30 ], may offer intriguing opportunities to better understand the patterns of substance use. When used with extreme care and constant human control, the vast amount of web data have also opened the door to the use of machine learning and generative artificial intelligence (AI) as interpretive and analytical support tools [ 31 , 32 ].…”