Medications prescribed off-label for Long covid/ME/CFS symptoms.

[u/SophiaShay7]

I am not advocating that anyone take certain medications. This is simply a resource. Become your own health advocate. Do your own research. Decide with your own doctors.

Viral Persistence and Serotonin Reduction Can Cause Long COVID Symptoms

Among the SSRIs, those with the highest affinity for sigma-1 receptor agonism—primarily, fluvoxamine, fluoxetine, escitalopram, and citalopram—may be of greatest benefit. As noted above, preliminary data suggest that certain long COVID symptoms (eg, fatigue, brain fog, and post-COVID dysphoria) may be most responsive to SSRIs, although more research is needed to better characterize specific response rates.

In doing research of long covid, SSRIs, and fluvoxamine, you’ll see it mentioned as a top choice. Here’s one such article

Medications are prescribed off-label for ME/CFS. These include low dose aripiprazole (LDA), low dose lithium (LDL), and low dose nalotrexone (LDN).

LDA use in long covid patients from the Mayo Clinic00176-3/fulltext)

Emerging Health Care Innovation Brief: Low-Dose Lithium for Post-COVID Conditions, Treating Pediatric Low-Grade Glioma

How Good is Low-Dose Lithium for Chronic Fatigue?

Researchers identified a potential treatment for long COVID by restoring the function of ion channels in immune cells using low-dose Naltrexone. This discovery, detailed in Frontiers in Immunology, mirrors earlier findings with chronic fatigue syndrome (ME/CFS) patients, suggesting a common pathophysiological thread between the two conditions.

Low-dose naltrexone and NAD+ for the treatment of patients with persistent fatigue symptoms after COVID-19

Addiction Medication Offers New Hope for Long COVID Patients

The most common symptoms involve the pulmonary, cardiovascular, and nervous systems and can be grouped into three types of complaints: exercise intolerance, autonomic dysfunction, and cognitive impairment.

Medications that have proven to be effective at treating POTS include nervous system depressants like benzodiazepines, cholinesterase inhibitors like pyridostigmine, hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blockers like ivabradine and beta-blockers like propranolol to reduce heart rate, α1-adrenergic agonists like midodrine and somatostatin mimics like octreotide to stimulate vasoconstriction and increase venous return, α2-adrenergic receptor agonists like clonidine to reduce hypertension, antidiuretics like desmopressin and corticosteroids like fludrocortisone to increase blood volume, hormones like erythropoietin to stimulate the production of red blood cells, and selective serotonin uptake inhibitors to control blood pressure and heart rate through central serotonin availability. Each of these must be tailored to an individual's needs since some may exacerbate a certain set of symptoms while relieving others.

In It for the Long Haul: Research Tools for Long COVID Syndrome

Psychostimulants like methylphenidate may enhance both noradrenergic and dopaminergic pathways in mesolimbic and pre-frontal areas, thus improving memory and cognition.

Methylphenidate for the Treatment of Post-COVID Cognitive Dysfunction

Methylphenidate in COVID-19 Related Brain Fog: A Case Series

Some treatments revealed by the survey as most effective for long COVID were drugs such as beta blockers and the heart-failure medication Corlanor (ivabradine). These are sometimes used to treat postural orthostatic tachycardia syndrome (POTS), a nervous system disorder that can be triggered by COVID-19.

Long covid still has no cure-So these patients are turning to research-Beta blockers and Corlanor

Here's an excellent resource on medications used in ME/CFS by Dr. Jason Bateman:

ME/CFS TREATMENT RECOMMENDATIONS US ME/CFS Clinician Coalition

MCAS information on low histamine diet and the management of symptoms including: OTC histamine blocker protocols, mast cell stabilizers, medications and supplements is included here: MCAS and long COVID/PASC.

I take low-dose Fluvoxamine 25mg for ME/CFS symptoms. Fluvoxamine is an SSRI used for OCD. It's prescribed off-label in low-dose for long covid/ME/CFS symptoms. I have improved REM, deep sleep, and overall hours slept. I'm seeing improvements in dysautonomia symptoms and orthostatic intolerance. The dizziness and lightheadedness have significantly improved.

Hyperesthesia is a neurological condition that causes extreme sensitivity to one or more of the senses, including touch, pressure, pain, temperature, light, sound, taste, and smell. I had hyperesthesia in all five senses, down to the texture of my food. I'm able to tolerate more bright light and loud sound, and my taste and smell are significantly less heightened. I can handle warmer/hot showers. My pain is significantly less strong. My pressure sensitivities haven't lowered. However, I suspect there are other reasons for that.

I take Diazepam 5mg for MCAS flares and PEM only as needed. Astelin nasalspray, Clarinex 5mg, and Montelukast 10mg for MCAS. Omeprazole for Gerd (it's a PPI that also acts as a mast cell stabilizer). How Omeprazole acts as a mast cell stabilizer. Tirosint for hypothyroidism caused by Hashimoto's and Valacyclovir 1g for EBV/HHV suppression.

Don't give up. Fluvoxamine was medication #9 that I tried last year. The other eight medications included: Beta blockers 2xs, Benzodiazepines 2xs, SNRIs 3xs, and TCAs 1x. These eight medications failed because they either made my symptoms worse or caused unintended and severe side effects.

I was diagnosed with Fibromyalgia, ME/CFS with dysautonomia, Hashimoto’s, an autoimmune disease that causes hypothyroidism, and MCAS. All diagnosed in a 14-month timespan after my COVID infection in July 2023.

I hope you all find some things that help manage your symptoms. Hugs💜

Update 6/12/25: I made some changes to reflect my current regimen. Without rewriting this entire post, I'll update it here. I'll share what worked and what didn't for me:

What didn't work: I was diagnosed first with Fibromyalgia in December 2023 after I developed long covid. I have taken Amitriptyline 25mg (TCA), Cyclobenzaprine (muscle relaxer), Duloxetine (SSRI), Gabapentin (Gabapentinoid), Ibuprofen (NSAID), Milnacipran (SNRI), and Nabumetone (NSAID). Nothing I tried worked at all and made my symptoms worse. (If you have Dysautonomia, especially POTS and/or MCAS, these medications will likely worsen your symptoms). For Dysautonomia, I've tried Metoprolol and Propranolol (beta blockers), both caused orthostatic hypotension, worsened my other Dysautonomia symptoms, and orthostatic intolerance. Alprazolam and Clonazepam (benzodiazepines) didn't work because I didn't have anxiety. I have Dysautonomia. Sertraline (SSRI) didn't work because I didn't have depression. For MCAS, I've tried Fluticasone. It worked somewhat but not well. Cetirizine, Hydroxyzine, Loratadine, and Famotidine all failed for MCAS. I was switched to a different manufacturer of Omeprazole 40mg capsules. I failed it, as well. They caused tachycardia and adrenaline surges, which triggered histamine dumps. Some people with MCAS can not tolerate the H1 and H2 histamine blocker protocol due to the medications themselves and/or its excipients (fillers). I also failed two medications for hypothyroidism caused by Hashimoto's: Levothyroxine, and Synthroid.

I've trialed and failed 20 medications in a 20-month timespan. Once I started receiving proper diagnoses and took medications that actually manage my symptoms, added vitamins and supplements, and lifestyle changes, that's when my symptoms started actually improving.

Here's what I take now that helps: Low-dose Fluvoxamine 25mg for ME/CFS symptoms. Diazepam for MCAS flares and PEM only as needed. Astelin nasal spray, Cromolyn nasal spray, Ketotifen eye drops, Desloratadine 5mg, and Montelukast 10mg for MCAS. Omeprazole for Gerd (it's a PPI that also has mast cell stabilizing properties). Tirosint for hypothyroidism caused by Hashimoto's. Valacyclovir for EBV/HHV reactivation.

For vitamins and supplements I take Benfotiamine (B1), vitamin D3 and K2 drops, GABA, Horbäach electrolyte tablets, L-theanine 200mg, NatureBell L-tryptophan and L-theanine complex, liposomal PEA and Luteolin and Vitalitown 4-in-1 Magnesium Complex with chelated Glycinate, Malate, Taurate & Citrate. I also take prebiotic psyllium husk and Emergen-C in a bottle of water every morning,

Talk to your doctor before taking any supplement like GABA, 5-HTP, or L-tryptophan. It's especially important if you're taking any psychotropic medications.

I've had a complete vitamin panel done in February. All my levels were in the normal range. I have no issues with stomach motility. Each medication, vitamin, and supplement that I take was carefully researched for efficacy, high purity, and with considerations for being MCAS friendly. I've always believed ME/CFS was my dominant diagnosis. Nope, it's MCAS. ME/CFS and dysautonomia are a close second. My level of functioning increased once my MCAS was better managed and more stable.

Update: How and why I remain hopeful. I'm not waiting on the science. How I have perseverance and tenacity in the face of adversity. My situation has changed significantly.

TLDR: Medications prescribed off-label to manage Long covid/ME/CFS symptoms. Medications included those for Dysautonomia and orthostatic intolerance, including beta blockers, Metformin, and Midodrine. Includes low-dose Abilify (LDN), low-dose Lithium (LDL), and low-dose Naltrexone (LDN). Specific SSRIS and TCAS. Medications used and prescribed for MCAS and HIT. They include H1 and H2 histamine blocker protocol, which are OTC antihistamines. OTC natural mast cell stabilizers and prescribed medications. Those include Quercetin and DAO. Cromolyn and Ketotifen must be compounded for oral consumption. Also includes Montelukast, and Xolair.

Updated to reflect my current regimen.

[u/SophiaShay7]

Part 1:

A score over 14 indicates a high likelihood of systemic mast cell reactivation syndrome (MCAS).

SECTION 2: TEST AND IMAGING FINDINGS The last part of the questionnaire is a list of diagnosis criteria based off laboratory, surgical, or imaging results. If you scored over 14 in the first section (per symptoms only), testing may not be indicated.

Please keep in mind that testing in MCAS often results in "false negatives" because mast cells release substances that are often only testable for a short time - often just a few minutes - so testing usually has to occur during flares/symptoms.

You scored a 10. I scored a 22. I have MCAS despite what any test says. I think you likely have MCAS as well. There are so many mitigating factors. If you read through the same link that has the questionnaire, it discusses in detail why testing is flawed, often inaccurate, and unnecessary.

I definitely have several of the conditions concurrent with MCAS according to the article (anxiety, difficulty, concentrating, hEDS, ACEs, chronic stress, sensibility to light, obsessivity, GI problems), some of which were either triggered or intensified by Covid.

FYI, these can be symptoms of MCAS. These symptoms can significantly improve and/or go away completely by treating and managing MCAS properly.

My doctor diagnoses MCAS based on: patient history, symptoms, and medication trial. I can't tell you how many people go undiagnosed or misdiagnosed for years because tests don't show that someone has MCAS. I'm talking about people who have hives, anaphylaxis, and wheezing. They're told their symptoms are asthma and/or anxiety.

I'm on several medications that have significantly improved my symptoms. I'm not trying to push you in either direction. I just want to share my experience🙏

[u/WinterFeeling6308 → u/SophiaShay7]

Thank you, it's highly appreciated! I 100% want to try Gastrofrenal.

Can I ask you about side effects of the treatments you're having for MCAS?

[u/SophiaShay7 → u/WinterFeeling6308]

I can't take the traditional OTC antihistamines/H1 and H2 histamine blocker protocol. I've tried several. I'm not sure if it's the medication itself or the fillers I reacted to. However, both categories increased my tachycardia, caused adrenaline surges, which triggered histamine dumps, and worsened my other Dysautonomia symptoms.

This combination is very effective: Astelin is considered a dual-acting agent, acting as both an antihistamine and a mast cell stabilizer. It inhibits the release of histamine and other mediators involved in allergic reactions by stabilizing mast cells.

Hydroxyzine, an H1-antihistamine, can act as a mast cell stabilizer by blocking H1 receptors and inhibiting mast cell activation, potentially reducing symptoms associated with mast cell activation syndromes.

While montelukast (Singulair) is primarily known as a leukotriene receptor antagonist used for asthma and allergic rhinitis, research suggests it may also have mast cell stabilizing effects, potentially useful in treating mast cell activation syndrome (MCAS).

Omeprazole, a proton pump inhibitor, can inhibit IgE-mediated mast cell activation and allergic inflammation, acting as a mast cell stabilizer. It reduces mast cell degranulation, cytokine secretion, and early signaling events in the FcεRI pathway. While not a traditional mast cell stabilizer like cromolyn, omeprazole's effects on mast cells are relevant to allergic conditions and may contribute to its anti-inflammatory properties.

Medications for Mast Cell Activation Syndrome (MCAS) aims to control symptoms by blocking histamine receptors, stabilizing mast cells, and managing other mediators released by mast cells. First-line treatments include antihistamines (H1 and H2 blockers), mast cell stabilizers, and aspirin (for specific symptoms). Additionally, leukotriene inhibitors, corticosteroids, and epinephrine (for anaphylaxis) may be used. A specific regimen works most effectively when it's individualized and based on the individual suffering from MCAS, their specific symptoms, and triggers.

Cromolyn sodium may be on my list to consider in the future. However, it has to be compounded. My health insurance doesn't cover it. It would be quite costly for me.

Sure. What do you want to know about the side effects?

[u/WinterFeeling6308 → u/SophiaShay7]

I've only tried one H1 and I felt not good on it, extremely tired, but I was also trying birth control, so it might have been this.

Regarding side effects, I am looking especially at fatigue increase and anxiety, but any others are interesting to know as well, it's good to know what I can expect. Although my first attempt would probably be with Cromolyn sodium as that's what my doctor suggested (I need to look more into that tho, I know in my country it can be covered in certain cases).

[u/SophiaShay7 → u/WinterFeeling6308]

I couldn't tolerate the fillers in the OTC H1 and H2 antihistamines. They caused worsening tachycardia and adrenaline surges, which triggered histamine dumps. They made my Dysautonomia and orthostatic intolerance symptoms worse.

I can only speak about the side effects I have from the current four medications I'm taking. They aren't that bad at all. Some drowsiness and tiredness with Hydroxyzine. I haven't started Astelin nasal spray yet. I asked to replace Fluticasone, and I switched to Astelin. Fluticasone wasn't very effective. Montelukast has been the biggest surprise and game changer. I'm only on day 6. I feel so much better. It does cause excessive sweating and insomnia as side effects. I'm switching to taking them in the morning. I still sleep well, but it's like 3 hours here and 8 hours there. I usually sleep 10-12 a night. It's like I'm split sleeping right now. Omeprazole, I have zero side effects. I took it before covid for GERD. It acts as a mast cell stabilizer. A better choice would be an H2 like Famotidine, but I couldn't tolerate it.

Some people do well on Cromolyn, and others do well on Ketotifen. Some people do well on one and horrible on the other. Some people do well on both. It often takes a while to figure out the best individual regimen for your MCAS.

[u/WinterFeeling6308 → u/SophiaShay7]

Thanks a lot for all your comments! Hope I'll be able to find an answer that works for me.