Can metformin cause anxiety
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Can Metformin Cause Anxiety?
Introduction to Metformin and Anxiety
Metformin is a widely used medication primarily prescribed for managing Type 2 diabetes. However, its effects extend beyond glucose regulation, influencing various neurological and psychiatric conditions. This article explores whether metformin can cause anxiety, drawing insights from multiple research studies.
Metformin's Anxiolytic Effects
Metformin and Anxiety Reduction in Animal Models
Several studies have demonstrated that metformin may actually reduce anxiety rather than cause it. For instance, research involving rats treated with metformin showed a decrease in anxiety-like behaviors induced by methamphetamine. The study suggested that metformin's neuroprotective effects might be mediated through the CREB/BDNF and Akt/GSK3 signaling pathways, which are crucial for brain health and function 1. Another study found that metformin facilitated the trafficking of GABAA receptors to the membrane, which is known to have anxiolytic effects 2.
Metformin's Impact on Anxiety in Insulin-Resistant Mice
In insulin-resistant mice, metformin was shown to decrease anxiety by normalizing the levels of branched-chain amino acids (BCAAs) and enhancing serotonergic neurotransmission in the hippocampus. This suggests that metformin's anxiolytic effects might be linked to its ability to improve metabolic health and neurotransmitter function 3.
Metformin and Anxiety in Women with PCOS
A study focusing on women with polycystic ovary syndrome (PCOS) found that metformin, when combined with lifestyle modifications, significantly reduced depression symptoms but did not have a significant effect on anxiety levels. This indicates that while metformin may help alleviate depressive symptoms, its impact on anxiety might be less pronounced in this population 4.
Short-Term High-Fat Diet and Anxiety
Research on mice subjected to a short-term high-fat diet revealed that metformin alleviated anxiety-like behavior induced by the diet. The study suggested that the anxiolytic effects of metformin could be due to its influence on gut microbiota and the activation of the AMPK pathway in anxiety-related brain regions 5.
Metformin's Role in Ovariectomy-Induced Anxiety
In ovariectomized rats, which serve as a model for menopause, metformin significantly reduced anxiety-like behaviors. The study attributed these effects to metformin's antioxidant properties, which help reduce oxidative stress in the prefrontal cortex and hippocampus, areas of the brain involved in anxiety and depression 6.
Conclusion
Current research suggests that metformin is more likely to reduce anxiety rather than cause it. Its anxiolytic effects have been observed in various animal models and specific human conditions, such as insulin resistance and PCOS. These effects are likely mediated through multiple pathways, including neurotransmitter regulation, antioxidant properties, and metabolic improvements. Therefore, metformin appears to have a protective role against anxiety rather than being a causative agent.
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Most relevant research papers on this topic
Protective role of metformin against methamphetamine induced anxiety, depression, cognition impairment and neurodegeneration in rat: The role of CREB/BDNF and Akt/GSK3 signaling pathways.
Metformin can protect the brain against methamphetamine-induced neurodegeneration by enhancing CREB/BDNF and Akt/GSK3 signaling pathways.
RCT
Animal Study
Highly CitedMetformin produces anxiolytic‐like effects in rats by facilitating GABAA receptor trafficking to membrane
Metformin shows potential in treating anxiety disorders by facilitating GABAA receptor trafficking, offering a potential alternative to benzodiazepines.
Rigorous JournalMetformin Promotes Anxiolytic and Antidepressant-Like Responses in Insulin-Resistant Mice by Decreasing Circulating Branched-Chain Amino Acids
Metformin reduces circulating branched-chain amino acids in insulin-resistant mice, promoting anxiolytic and antidepressant-like effects, suggesting it could be used as an add-on therapy for metabolic and mental disorders.
Non-RCTAnimal Study
Very Rigorous JournalHighly CitedMetformin Improves the Depression Symptoms of Women with Polycystic Ovary Syndrome in a Lifestyle Modification Program
Metformin may help manage depression symptoms in women with PCOS when combined with lifestyle modifications, but its potential antidepressant effect needs further randomized double-blind placebo-controlled trials.
Observational StudyRigorous JournalEffect of Metformin on Short-Term High-Fat Diet-Induced Weight Gain and Anxiety-Like Behavior and the Gut Microbiota
Metformin effectively reduces short-term high-fat diet-induced weight gain, anxiety-like behavior, and gut microbiota changes, potentially due to its anxiolytic effect in anxiety-related brain nuclei.
Non-RCTAnimal StudyProtective effect of metformin against ovariectomy induced depressive- and anxiety-like behaviours in rats: role of oxidative stress
Metformin treatment significantly decreased depressive behavior and oxidative stress in the prefrontal cortex of ovariectomized rats, suggesting potential therapeutic use in women with depression in surgical menopause or gonadal hormone deficiency.
RCTAnimal StudyRigorous JournalPossible involvement of agmatine in neuropharmacological actions of metformin in diabetic mice.
Metformin and agmatine combination effectively reverses memory impairment, depression, and anxiety-like behaviors in diabetic mice, suggesting potential therapeutic strategies for diabetes-related disorders.
Non-RCTAnimal StudyRigorous JournalThe effect of the anti-diabetic drug metformin on behavioral manifestations associated with ovariectomy in mice
Metformin improves cognitive impairments and anxiety in ovariectomized mice, suggesting it could be a novel therapeutic strategy for treating ovariectomy-related conditions.
Metformin: A Prospective Alternative for the Treatment of Chronic Pain
Metformin shows potential in treating chronic pain and its comorbidities, such as anxiety, depression, and cognitive impairment, through its effects on neuronal plasticity and mTORC1 signaling.
Literature ReviewMetformin modulates microbiota-derived inosine and ameliorates methamphetamine-induced anxiety and depression-like withdrawal symptoms in mice
Metformin improves methamphetamine withdrawal-induced anxiety and depression-like behaviors in mice by modulating gut microbiota and restoring inosine levels, highlighting the role of gut microbiota in substance use disorders and withdrawal symptoms.
Non-RCTAnimal Study
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