Medications like Ozempic and Wegovy are flying off prescription pads almost as fast as patients are dropping pounds from taking them.
Both medications are a formulation of semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RAs), used for managing diabetes and obesity before physicians recognized their potential for promoting weight loss.
Less commonly advertised are the side effects of these drugs, including nausea, vomiting, diarrhea, and constipation, and more serious risks like pancreatitis, thyroid tumors, and allergic reactions. Now a new study from the journal Diabetes, Obesity, and Metabolism has examined an even more poorly understood aspect of GLP-1RAs – their impact on mental health.
The Study
Researchers pulled a 10 percent random sample from the Australian Pharmaceutical Benefits Scheme (PBS) that included data from over 1.7 million individuals over the ten year period, from 2012 to 2022.
Subjects were divided into two groups: those who had been prescribed GLP-1RAs and those who had not. After adjusting for various factors that could influence the study’s results, such as age, sex, other medications, and overall health status, the researchers compared the level of antidepressant prescribing between the two groups.
In the study’s one-year cross-sectional analysis of 2022 data, 21 percent of the 1,746,391 individuals were dispensed an antidepressant. But in the subgroup prescribed a GLP-1RA, the rate of antidepressant prescriptions was much higher – 34 percent.
Researchers noted that overall, about 2 percent of people given antidepressants over the one year period in 2022 were prescribed GLP-1RAs over the ten year period. And people who took GLP-1RAs were also more likely to need antidepressants compared to those who didn’t take them. Although this percentage may seem low, the results suggest a potential connection between taking a GLP-1RA and the need for antidepressants, the researchers noted.
The Interpretation
Several possible explanations exist for why GLP-1RA users are more likely to receive prescriptions for antidepressants.
According to the researchers, the medications themselves might influence mood directly. Or, the increased interaction with healthcare providers among those with diabetes and obesity may lead to more frequent diagnosis and treatment of mood disorders.
Confounding factors such as underlying health conditions, which are more prevalent in patients requiring GLP-1RAs, might also contribute to both the need for these medications and a higher incidence of depression, the authors speculated.
The researchers also suspect that there could be biological mechanisms that link GLP-1RA use to depression. It’s possible that the drugs have an influence on brain chemistry that alters mood, although the exact pathways remain unclear. They propose that the increased dispensing of antidepressants among users of GLP-1RAs might indicate a potential impact of these diabetes medications on mood, which warrants further investigation.
Interestingly, the researchers found no association between the type of antidepressant given and GLP-1RAs.
“We also found that the association with GLP-1 RAs was not specific to a particular class of antidepressant, although it was particularly strong for duloxetine. The association between the dispensing of GLP-1 RAs and antidepressants was greater for men than women and did not extend to other psychotropic medicines, such as antipsychotics,” they wrote in the study.
Looking Ahead
The researchers acknowledged that, while their study is robust, involving a large dataset and multiple study designs, there are limitations that could affect the generalizability of the results. For instance, the PBS database does not capture all instances of medication use, such as those not subsidized or prescribed outside of formal channels, which could lead to underestimation of GLP-1RA use.
Healthcare providers should carefully monitor the mental health of patients treated with GLP-1RAs. The medications do appear to be effective for weight loss but their use could have unintended effects on mental health that require careful management and further scientific exploration.
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