Does metformin cause anxiety
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Summary
7 papers analyzed
These studies suggest metformin may reduce anxiety and have anxiolytic effects.
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The Impact of Metformin on Anxiety: A Comprehensive Review
Introduction to Metformin and Anxiety
Metformin, a widely used antidiabetic medication, has been explored for its potential effects on various psychiatric conditions, including anxiety. This article synthesizes findings from multiple studies to determine whether metformin causes or alleviates anxiety.
Metformin's Anxiolytic Effects in Animal Models
Protective Role Against Methamphetamine-Induced Anxiety
Research has shown that metformin can mitigate anxiety induced by methamphetamine in rats. In a study where rats were administered methamphetamine, metformin significantly reduced anxiety-like behaviors. This effect was attributed to the activation of CREB/BDNF and Akt/GSK3 signaling pathways, which are crucial for neuroprotection and cognitive function.
GABAA Receptor Trafficking
Another study highlighted that metformin produces anxiolytic-like effects by facilitating the trafficking of GABAA receptors to the membrane. This mechanism is similar to how benzodiazepines work, suggesting that metformin could be a potential alternative for anxiety treatment without the risk of dependence associated with benzodiazepines.
High-Fat Diet and Anxiety
In mice fed a high-fat diet, metformin was found to alleviate anxiety-like behavior. This effect was linked to the drug's ability to reduce circulating branched-chain amino acids (BCAAs), which in turn enhanced serotonergic neurotransmission in the hippocampus. The study suggested that metformin's anxiolytic effects might be due to its impact on metabolic pathways and neurotransmitter systems.
Clinical Evidence in Humans
Polycystic Ovary Syndrome (PCOS) and Anxiety
A study involving women with PCOS, a condition often associated with anxiety, found that metformin significantly reduced depression symptoms but did not have a notable effect on anxiety levels. This suggests that while metformin may help with depressive symptoms, its impact on anxiety in PCOS patients is less clear.
Short-Term High-Fat Diet and Anxiety
In a short-term study on mice, metformin was shown to reduce anxiety-like behavior induced by a high-fat diet. The anxiolytic effect was potentially linked to changes in gut microbiota and the activation of the AMPK pathway in anxiety-related brain regions.
Ovariectomy-Induced Anxiety
In ovariectomized rats, which serve as a model for menopause, metformin reduced anxiety-like behaviors. This effect was associated with a decrease in oxidative stress in the prefrontal cortex and hippocampus, suggesting that metformin's antioxidant properties might play a role in its anxiolytic effects.
Conclusion
The current body of research indicates that metformin does not cause anxiety; rather, it appears to have anxiolytic effects in various animal models and specific human conditions. These effects are likely mediated through multiple pathways, including GABAA receptor trafficking, reduction of oxidative stress, and modulation of neurotransmitter systems. However, more clinical trials are needed to fully understand the potential of metformin as a treatment for anxiety in humans.
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