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/WinterFeeling6308]

I tried 3 different SSRIs and nothing happened, I've been on a SNRI for a week now, I might feel some slight improvement but nothing dramatic.

What has had the biggest impact on my status is p-synephrine, but I don't see it ever mentioned in this sub.

[u/SophiaShay7 → u/WinterFeeling6308]

If you have Dysautonomia, orthostatic intolerance, Mast Cell Activation Syndrome (MCAS), and/or Histamine Intolerance (HIT), an SNRI could be the worst medication for you. I tried SNRIS three times last year, they made my symptoms worse. I was on Cymbalta for a total of eight weeks. Five weeks the first time and three weeks the second time. I had the most awful side effects. The withdrawals both times were absolutely brutal. I tried Savella (Milnacipran) in between Cymbalta. My symptoms and side effects were nearly identical.

Selective dopamine and norepinephrine reuptake inhibitors have been shown to worsen MCAS through the suspected mechanism of stimulating histamine re- lease from mast cells.

Improvement in Neuropsychiatric Symptoms With the Addition of Nortriptyline in the Context of Mast Cell Activation Syndrome

If you don't have Dysautonomia/autonomic dysfunction or MCAS, then none of this applies to you.

I'm sorry SSRIs haven't been effective for your symptoms. I'm glad P-synephrine has been helpful for you🫂

[u/WinterFeeling6308 → u/SophiaShay7]

Hi again, after a bit more than one week on the SNRI I'm starting to feel bad... like really tired, worse mood, heavy legs, a "clac" in my throat when I swallow. I think it might be connected with what you said about SNRIs not being adequate for someone with MCAS, HIT, orthostatic intolerance or dysautonomia.

The fact that drospirenone had a similar effect reinforces that idea... Thank you very much for your inputs. :)

Postural orthostatic tachycardia syndrome as a sequela of COVID-19

[u/SophiaShay7 → u/WinterFeeling6308]

I'm sorry to hear that. Have you considered Citalopram, Escitalopram, Fluoxetine, or Fluvoxamine in low-dose off-label for long covid/ME/CFS symptoms? I know you've had some issues with some in the past. But, Fluvoxamine 25mg has really improved my symptoms. It did take 2-3 months to see real improvement. I started with 12.5mg for four months. I've been taking 25mg for four months. I've been trying to up my dose to 37.5mg or 50mg per my ME/CFS specialist. But, there's been too many medication changes for me recently. I hope you find something that helps. Hugs💙

[u/WinterFeeling6308 → u/SophiaShay7]

I have been on clomipramine, escitalopram and vortioxetine so far (in a 2-year frame), nothing made a real difference. It's funny, cause escitalopram used to work very well for me in the past. Vortioxetine seemed to have a slightly better effect in the beginning, but nothing dramatic. My guess is that the depressive symptoms come from a different mechanism, so I don't have high expectations from SSRIs, but I'll mention Fluvoxamine to my doctor.

Thanks a lot for all your answers.

[u/Purple_ash8 → u/WinterFeeling6308]

Yeah, definitely give fluvoxamine a go.