Practical Neuropsychiatry

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Metformin and Long COVID prevention

Some of the biggest barriers to treatment since the beginning of the COVID era have been hype and misinformation, and in many ways this was a problem since the wealth of literature on Myalgic Encephalomyelitis in the 80s. Prejudice from medical providers has surely been at the root of many problems, but both doctors and political actors have discussed everything from potential miracles to outright prejudice towards patients. There is plenty of good information out there, but separating it from the bad is no easy feat even for well trained, well intentioned providers.

With chronic diseases, a whole host of treatments have been popularized despite having had limited or no benefit in various trials. Some of these have been a misappropriated hope that more aggressive treatment of the infection would reduce post-infectious symptoms. From months of antibiotic treatment for lyme (antivirals for COVID) to devices that claim they use Ultrasound “dialed to the frequency of the Lyme Bacteria”, patients will cling to these promoted cures as if they are their final hope. Doctors at Chronic Lyme clinics have been the main ones promoting them, some from a genuine desire to grasp for anything that might help and others from a desire to charge for the procedures. 


Mainstream medicine has generally fled from these treatments for many reasons. Some physicians, of course, have decided that these illnesses are “not real”. Others have seen so many patients mystified by these elusive and expensive cures, and have become jaded. The data has repeatedly failed to impress or simply not been available in a peer review publication, and some of the treatment mechanisms as translated through the patients are so bizarre, that it all becomes a noisy burden to the primary care team, leading to skepticism and cynicism with any new proposed treatment. 


Now I must clarify, there are a lot of “hints of truth” to those treatments, though they are not a magic cure. Hydroxychloroquine, lauded by conspiracy theorists everywhere,  has been repeatedly shown to have little to no effect on treating acute infections like Covid-19.It has, however, been well studied in many different autoimmune conditions from Rheumatoid Arthritis to Sjogren’s disease and found to have usefulness. Unfortunately, any claims that it treats, prevents, or cures Long-COVID has not been validated yet. In fact, when (in the main article I will link to below) they have looked at this question specifically it hasn’t shown much benefit if any. Many would propose that hydroxychloroquine “might help” before the study results came out, but physicians should never start using treatments before there is data to show it is safe, and at least a hint of effectiveness in humans. Not only are there known severe medical risks with hydroxychloroquine for vision, some of the core symptoms of Long-COVID are common side effects like confusion, headaches and dizziness. The most important thing is that many rigorous scientific studies have been done on it in various conditions and in some cases (lupus patients) it seems to be helpful in brain fog/mood/migraine, while in other populations (like Sjogren’s) it seems to worsen those same symptoms. Therefore, without data in ME and Long COVID I cannot recommend it, though if someone starts it for a rheumatologic condition I wouldn’t be surprised to see either improvement or worsening of their Long-COVID symptoms. 


I say all of this to explain why I believe that one of the biggest breakthroughs in management of Long-COVID, with very good data to supports its use, has been nearly completely ignored by most medical providers. They are so used to seeing patients obsessed with miracle cures, some even bringing articles (usually opinion pieces or non-peer reviewed publications) that Doctors seem to be waiting for some government agency or Pharmaceutical representative to tell them what to do. 

So what is this breakthrough? A very old, very safe drug named Metformin. Before I present the data on metformin, I must admit that it has been quite difficult to convince PCPs to even let me prescribe it. Metformin, to them, is a diabetes drug. The mechanisms of action they are taught about with it are to do with sugar absorption and processing. Compared to Ivermectin and Plaquinil (both of which are taught in relation to either infectious diseases or inflammatory conditions), metformin makes even less sense. I don’t blame them. However, when in 2023, the Lancet (one of the most well respected peer-reviewed journals) published this article, AND that information spread quickly to news outlets across the country, I cannot understand why they didn’t learn about it. 


But Metformin has had a very long history of study for conditions like Long-COVID. This article is a very good thorough review into the mechanisms by which metformin affects various immune system components. This article reviews a 30 year history if its study in patients with chronic pain/fatigue, showing it to be quite helpful in reducing chronic musculoskeletal pain. However, I have had many PCPs tell patients not to take it despite my offering to provide these articles and rationale. 


So what is the simple truth about metformin? It definitely isn’t a cure-all for the immune system. It hasn’t yet been well studied with regards to most of the Long-COVID symptom clusters. There is a real risk of stomach upset and even diarrhea which may make the benefits not worth the side effects for a small subset of patients predisposed to the diarrhea. HOWEVER, there is plenty of data to support its use in gradual and small but impactful benefits in chronic muscle pain and fatigue, mostly in the setting of a Fibromyalgia diagnosis. A very brief 2 week course of metformin at onset (positive test) of COVID seems to reduce the development of Long-COVID symptoms. All of this makes sense based on the research into the immune system modifying effects of Metformin that are wholly separate from its use in diabetes. 


If you’d like a neuropsych health consult to discuss this plan to help you find a path forward in seeking treatment, don’t hesitate to reach out.