In late 2017, the FDA approved the first and best-known GLP-1 receptor agonist, which you’ll probably know as “Ozempic.” At first it was only recognized as appropriate to treat Type 2 diabetes, but just over four years later, a 2mg dose of the same drug received FDA approval for weight management. These medications then surged in popularity—according to a health tracking poll by KFF, as of May 2024 as many as 1 out of every 8 American adults had taken a GLP-1 drug. But by the fall of 2023, the system through which physicians notify the FDA of “adverse events” had already accumulated almost 500 reports of possible mental health side effects attributed to the GLP-1 drugs. Anxiety, depression, and even suicidal ideation in patients taking them had been reported by doctors across the country. NPR reported in September of 2024 that in 96 of these adverse events, the patients in question had experienced suicidal thoughts; five of these patients died.
To be clear, the FDA’s database is not designed for cause-and-effect reasoning, so it’s not possible to assign full responsibility for these serious psychological conditions to GLP-1 drugs. But a simultaneous groundswell on social media seemed focused on the same phenomena, as a 2023 study by the National Institute of Health documented (Arillotta et al., 2023). Data were collected from several social media websites, including TikTok, YouTube, and Reddit, and the resulting information was broken down via the use of an AI spreadsheet analysis platform called Numerous. Most social media comments pertaining to GLP-1 receptor agonists and psychological symptoms focused on “sleep-related issues, including insomnia,” but also called out “anxiety… depression… and mental health issues in general.” Again, some apparent links between weight loss medications and psychological side effects had been established, but without any clear causal link between them. Perhaps, for example, people who elect to use GLP-1 drugs are already more likely to experience anxiety or depression. Social media users also noted that the drugs also appeared to be losing their effectiveness over time, which could result in disappointment or in feelings of being “stuck;” thus, the researchers here may have found it hard to tease apart the drug’s potentially depressogenic consequences from the results of the drug’s failure to have its hoped-for effect.
The next step was to perform another, bigger study, with more patients and more adverse events, collected over a larger period of time. Sure enough, a subsequent study of the FDA’s Adverse Event Reporting System was conducted, using a much larger sample. Last year Chen, W. et al. reviewed 181,238 adverse event (AE) reports for psychological symptoms, then segregated 8,240 AEs as useful and relevant. This study found a “significant association” between GLP-1 drugs and “the development of specific psychiatric AEs.” Chen listed included “eight categories of psychiatric AEs, namely, nervousness, stress, eating disorder, fear of injection, sleep disorder due to general medical condition—insomnia type, binge eating, fear of eating, and self-induced vomiting.” The study even provided a median time to onset, which was 31 days (although it varied across the drugs)—suggesting that, among those people who reported negative psychological outcomes, most experienced their symptoms about a month after first taking the drugs.
Later studies found even more serious effects. In the journal Nature, Kornelius et al. published a 2024 paper identifying a “significant association between GLP-1… treatment and an [sic] 98% increased risk of any psychiatric disorders. Notably, patients on GLP-1 RAs exhibited a 195% higher risk of major depression, a 108% increased risk for anxiety, and a 106% elevated risk for suicidal behavior.” This study focused on psychiatric conditions in patients with obesity, and included over 162,000 patients split into matched pairs (meaning: one control subject, one experimental subject). Not all GLP-1 drugs had the same psychiatric effects: Ozempic was associated with an “approximately 2.4-fold increase in risk” of suicidal ideation, when compared to Wegovy and Saxenda. Plus, different types of patients had different drug outcomes. As Kornelius et al. (2024) wrote, “Females had a higher risk of anxiety and suicidal ideations or attempts compared to males. Younger participants (18–49 years) exhibited a higher risk of suicidal ideations or attempts, while older participants (≥ 70 years) had a lower overall risk of psychiatric diseases. Additionally, racial differences were observed, with Black patients showing a higher risk of suicidal ideations or attempts compared to White and Asian patients.” The study urged physicians to consider their patients’ psychiatric histories before prescribing drugs like Ozempic.
But just as the potentially bad news about GLP-1 receptor agonists had begun to create a clear picture, other studies complicated it by finding that sometimes, these drugs can have antidepressant effects. In the American Journal of Geriatric Psychiatry, Chen, X et al (2024) write that these drugs induced “significant reductions in the depression rating scales compared to control treatments,” and were found to “alleviate depressive symptoms” in patients with Type 2 diabetes. And when using only the results of randomized controlled trials—which many people say produce the most reliable type of scientific data—GLP-1 receptor agonists showed a significant positive effect on depressive symptoms in adults.
So as of now, the jury is still out, and a final understanding of the psychological effects of the current crop of weight loss drugs has not yet been achieved. Research on the risks and benefits of GLP-1s is still being conducted, and thousands of new social media comments are building up every day. Taking these drugs may well be associated with a risk of psychological harm—but even so, your physician may also be able to provide evidence of medical risks inherent in maintaining a heavier-than-average weight. In any case, all weight-related decisions are extremely personal and can be very complex; it’s unfortunate that for now, the potential risks inherent in GLP-1 use may only complicate the picture further.