What’s next?

jaybee00

Senior Member
Messages
536
Likes
852
Search forum for ceftriaxone and Rocephin for accounts. Complete remission of brain fog.

From wiki:
“Ceftriaxone seems to increase excitatory amino acid transporter-2 pump expression and activity in the central nervous system, so has a potential to reduce glutamatergic toxicity.[29][30]”


The 2 epilepsy drugs have helped others with brain fog.
 

junkcrap50

Senior Member
Messages
1,187
Likes
2,647
Rexulti Cariprazine & Abilify are in the same class of drugs and all have worked for patients.
Any more info on these other drugs? Are they also taken as very low dose like abilify in me/cfs? Did others work when Abilify failed? Did the effect on the other drugs fade/stop working too after a while?
 
Last edited:

Learner1

Senior Member
Messages
6,278
Likes
11,642
Location
Pacific Northwest
It’s called delimmun by Kora Healthcare
Apparently "this content is restricted in my region"... Wonder what's available in the US...
Screenshot_20210717-172755.png

Tyrosine could work… I can’t get Kuvan in Germany. Ferritin is normal
Looks like a subsidiary of Merck sells it in Europe?

https://www.thepharmaletter.com/article/merck-serono-launches-kuvan-in-europe

Ceftriaxone
Topiramate or phenytoin
"ceftriaxone caused more extensive and prolonged disruption of the gut microbiome than piperacillin/tazobactam. Antibiotics induce gut dysbiosis, thereby enabling colonization by drug-resistant pathogens."

"ceftriaxone sodium administration resulted in gut microbiota dysbiosis, intestine histological lesions, growth inhibition, spleen index reducing. The immune defense ability reduced as serum IgG and mucus SIgA decreased significantly. "

"Expert opinion: Mitochondrial-toxic AEDs may trigger or worsen an MID or may be even fatal in single cases. The AED with the most well-known mitochondrial toxicity is valproic acid (VPA), which has been known to exhibit a deleterious effect in patients with POLG1 mutations and patients with myoclonic epilepsy with ragged red fibers syndrome and VPA should only be applied in MIDs in case of a drug-resistant status epilepticus. AEDs other than VPA, which may affect the mitochondrial metabolism, include phenobarbital, carbamazepine, phenytoin, oxcarbazepine, ethosuximide, zonisamide, topiramate, gabapentin and vigabatrin. AEDs which interfere with mitochondrial function should be avoided whenever justifiable to the patient's well-being."

"Topirimate - Important warnings
Metabolic acidosis warning: This drug may raise your risk of a medical condition called metabolic acidosis. This can come on with no symptoms. Or it may happen with side effects on the kidneys (kidney stones), bones (osteoporosis, increased risk of broken bones), or growth delays. Symptoms of this condition include:

hyperventilation (rapid breathing)
tiredness
loss of appetite
changes in your heart rhythm
trouble thinking clearly

Vision loss warning: This drug can cause a blockage of fluid in your eye, which results in increased pressure in the eye. This can lead to permanent vision loss.

Birth defects warning: This drug can cause birth defects if it’s taken during pregnancy. These birth defects can occur early in pregnancy, before a woman even knows she’s pregnant. Women of childbearing age should use effective forms of birth control while taking this drug. Ask your doctor about good options. This drug can cause birth control pills to be less effective.

Severe skin reaction warning: Severe skin reactions (Stevens-johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) may happen when taking this drug. They can cause severe health problems that can be deadly. Get medical help right away if you experience any of these signs:"

"AEDs may influence various mitochondrial functions or structures in a beneficial or detrimental way. There are AEDs in which the toxic effect outweighs the beneficial effect, such as valproic acid (VPA), carbamazepine (CBZ), phenytoin (PHT), or phenobarbital (PB). "

"More common side effects in people taking Rexulti for depression include:

akathisia (feelings of restlessness and inability to sit still)
weight gain
headache


More common side effects in people taking Rexulti for schizophrenia include:

akathisia
weight gain

Serious side effects that have been reported and their symptoms include:

Neuroleptic malignant syndrome (a possibly life-threatening reaction to certain drugs). Symptoms can include:

confusion
fast heart rat
fever
high blood pressure or low blood pressur
rigid muscle
sweating
Tardive dyskinesia (unintentional muscle movements). Symptoms can include
excessive blinking
trouble controlling movements of your face or tongue
waving your arms without meaning t
High blood sugar levels. Symptoms can include
feeling unusually thirsty or hungry
needing to urinate more frequently than usual
weakness
tiredness
Orthostatic hypotension (a sudden decrease in blood pressure when changing positions). Symptoms can include
dizziness when you stand up after you’ve been sitting or lying down
Seizures (unusual electrical activity in the brain). Symptoms can include
loss of consciousness
confusion
uncontrollable movements of your arms or leg
Trouble swallowing caused by neck spasms (uncontrolled muscle tightening). Symptoms can include
trouble breathing
food getting caught in your throat
Body temperature regulation problems. Symptoms can include
trouble cooling down after you exercise or are exposed to heat
Stroke (decreased or blocked blood flow to the brain), which is more commonly reported in older people using Rexulti. Symptoms can include
confusion
numbness or weakness in your arms, face, or leg
trouble speaking
trouble seeing from one or both of your eye
Increased blood cholesterol or triglyceride levels. This usually doesn’t cause noticeable symptoms, but would show on blood test results
Risk of death in certain older adults.
Risk of suicidal thoughts and behaviors in certain people.
Weight gain.
Allergic reaction."


As someone harmed by 5 medications taken as prescribed for the indications they were prescribed for, it seems wise to consider whether using one of these drugs off-label might actually worsen ones situation.

It might be wiser to dig into the metabolomics/biochemistry of the problems one has and to individualize medicine to treat what's actually going on rather than whacking it with a sledgehammer and hoping/praying for the best...
 

jaybee00

Senior Member
Messages
536
Likes
852
There are risks for everything. Be aware of the risks and let the patient make the decision--informed consent.

side effects for aspirin:


In Summary
More frequently reported side effects include: dyspepsia, epigastric discomfort, heartburn, and nausea. See below for a comprehensive list of adverse effects.

For the Consumer
Applies to aspirin: oral capsule extended release 24 hr, oral tablet, oral tablet chewable, oral tablet enteric coated


Side effects requiring immediate medical attention
Along with its needed effects, aspirin may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking aspirin:

Incidence not known

Abdominal or stomach pain, cramping, or burning
black, tarry stools
bloody or cloudy urine
change in consciousness
chest pain or discomfort
confusion
constipation
convulsions, severe or continuing
dark urine
decreased frequency or amount of urine
diarrhea
difficult breathing
drowsiness
fainting
fast breathing
feeling that something terrible will happen
fever
general tiredness and weakness
greatly decreased frequency of urination or amount of urine
headache
heartburn
increased thirst
indigestion
irregular heartbeat
light-colored stools
loss of appetite
loss of consciousness
lower back or side pain
muscle cramping and weakness
muscle tremors
nausea or vomiting
nervousness
numbness or tingling in the hands, feet, or lips
panic
rapid, deep breathing
restlessness
seizures
skin rash
stomach cramps
swelling of the face, fingers, or lower legs
unusual bleeding or bruising
unusual tiredness or weakness
vomiting of blood or material that looks like coffee grounds
weakness or heaviness of the legs
weight gain
yellow eyes and skin
Side effects not requiring immediate medical attention
Some side effects of aspirin may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.


Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Incidence not known

Acid or sour stomach
anxiety
belching
dizziness
dry mouth
hyperventilation
irritability
shaking
stomach discomfort, upset, or pain
trouble sleeping
unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness
Managing side effects (general information)
For Healthcare Professionals
Applies to aspirin: compounding powder, oral capsule extended release, oral delayed release capsule, oral delayed release tablet, oral gum, oral powder for reconstitution, oral tablet, oral tablet chewable, oral tablet disintegrating, oral tablet dispersible, oral tablet extended release, rectal suppository

Gastrointestinal
Common (1% to 10%): Dyspepsia,

Frequency not reported: GI bleeding, ulceration, perforation, nausea, vomiting, pancreatitis, gastric irritation, GI erosions, gastritis, melena, hematemesis, gingival bleeding[Ref]

Renal
Frequency not reported: Interstitial nephritis, papillary necrosis, renal insufficiency and failure[Ref]

Hematologic
Common (1% to 10%): Increased bleeding tendencies

Rare (0.01% to 0.1%): Aplastic anemia agranulocytosis, thrombocytopenia

Frequency not reported: Prolongation of prothrombin time, disseminated intravascular coagulation, coagulopathy, antepartum and postpartum bleeding, anemia[Ref]

Hypersensitivity
Rare (0.01% to 0.1%): Anaphylactic reactions including shock

Frequency not reported: Urticaria, angioedema, skin rashes[Ref]

Dermatologic
Uncommon (0.1% to 1%): Urticaria

Rare (0.01% to 0.1%): Steven-Johnson syndrome, Lyell's syndrome, erythema nodosum, erythema multiforme

Frequency not reported: Purpura, hives[Ref]

Hepatic
Frequency not reported: Transient elevations of hepatic enzymes, hepatitis, Reye's syndrome, hepatic insufficiency[Ref]

Metabolic
Frequency not reported: Thirst, dehydration, hyperkalemia, metabolic acidosis, respiratory alkalosis, hypoglycemia, hyperglycemia, hyperuricemia, salt and water retention[Ref]


Cardiovascular
Rare (0.01% to 0.1%): Hemorrhagic vasculitis

Frequency not reported: Dysrhythmias, hypotension, tachycardia[Ref]

Nervous system
Frequency not reported: Cerebral edema, coma headache, subdural or intracranial hemorrhage, seizures, lethargy, dizziness[Ref]

Other
Frequency not reported: Fever, hypothermia, hearing loss, tinnitus (at high doses), hearing disturbances[Ref]

Musculoskeletal
Frequency not reported: Rhabdomyolysis[Ref]

Respiratory
Frequency not reported: Hyperpnea, pulmonary edema, tachypnea, epistaxis, dyspnea, bronchospasm, asthma[Ref]

General
The more commonly experienced adverse effects include indigestion, dyspepsia, bleeding, and bruising.[Ref]

Genitourinary
Rare (0.01% to 0.1%): Menorrhagia

Frequency not reported: Proteinuria[Ref]

Psychiatric
Frequency not reported: Agitation, confusion[Ref]
 

hapl808

Senior Member
Messages
994
Likes
2,524
I've also thought dopamine / adrenaline could be an issue, as mental exertion (even enjoyable exertion) or physical exertion both lead to PEM crashes. Unfortunately that's combined with pretty extreme weakness (I can't stand up without help), so that's quite limiting as you well know. I've also looked at glutamate / GABA - it's very hard to differentiate some of the neurotransmitter functions and balance.

I have tried various amino acids under the theory of precursors, etc. I only tried the L-Tyrosine version, but I didn't notice any effects. Maybe the other form would be more effective. I think when it's a combination of weakness and energy, it seems much tougher to fix. Many years ago when I was mild or moderate, there were many things that were helpful in different ways. Once I became more severe, the positive effects mostly dissipated.

I also have looked at Wellbutrin with interest, both for its effects on dopamine / adrenaline, and Goldstein's affinity for it. I have not tried that as of yet - I hope you have good results.
 
Messages
2,287
Likes
7,568
I've also thought dopamine / adrenaline could be an issue, as mental exertion (even enjoyable exertion) or physical exertion both lead to PEM crashes. Unfortunately that's combined with pretty extreme weakness (I can't stand up without help), so that's quite limiting as you well know. I've also looked at glutamate / GABA - it's very hard to differentiate some of the neurotransmitter functions and balance.

I have tried various amino acids under the theory of precursors, etc. I only tried the L-Tyrosine version, but I didn't notice any effects. Maybe the other form would be more effective. I think when it's a combination of weakness and energy, it seems much tougher to fix. Many years ago when I was mild or moderate, there were many things that were helpful in different ways. Once I became more severe, the positive effects mostly dissipated.

I also have looked at Wellbutrin with interest, both for its effects on dopamine / adrenaline, and Goldstein's affinity for it. I have not tried that as of yet - I hope you have good results.
I'll report if I have any positive results.
 

Viala

Senior Member
Messages
367
Likes
997
@Martin aka paused||M.E. I've also considered dopamine deficiency as one of imporant factors. I tested tyrosine but for me it was a no go, if I didn't have side effects I would try to increase the doses and test it for longer. I tried a lot of aminoacids though successfully for other issues, I could see positive results within a few days or a week so they act quite quickly, sometimes even within hours, so it is best to try low doses first.

I remember an interview with Jordan Peterson who took wellbutrin for his depression, he described his condition as having no energy and feeling like moving through molasses, hard to move, he also mentioned great relief when his muscles finally relaxed, all of it struck me as something similiar to what we experience with CFS. It worked well for his depression. I didn't try wellbutrin though, I am more an advocate of more natural approaches, but I was always curious if it could help. Here is the excerpt from that interview.
 
Messages
2,287
Likes
7,568
@Martin aka paused||M.E. I've also considered dopamine deficiency as one of imporant factors. I tested tyrosine but for me it was a no go, if I didn't have side effects I would try to increase the doses and test it for longer. I tried a lot of aminoacids though successfully for other issues, I could see positive results within a few days or a week so they act quite quickly, sometimes even within hours, so it is best to try low doses first.

I remember an interview with Jordan Peterson who took wellbutrin for his depression, he described his condition as having no energy and feeling like moving through molasses, hard to move, he also mentioned great relief when his muscles finally relaxed, all of it struck me as something similiar to what we experience with CFS. It worked well for his depression. I didn't try wellbutrin though, I am more an advocate of more natural approaches, but I was always curious if it could help. Here is the excerpt from that interview.
I try many supplements and I’m not a fan of taking an AD. But if it makes me better… I took the first one this morning and feel a slight increase in energy but too early to tell…
 

Viala

Senior Member
Messages
367
Likes
997
I try many supplements and I’m not a fan of taking an AD. But if it makes me better… I took the first one this morning and feel a slight increase in energy but too early to tell…
I am also not a fan of AD, maybe at some point I will try it, I still test another treatments. I hope you will feel much better with loads of energy, keeping my fingers crossed.
 

nerd

Senior Member
Messages
863
Likes
2,537
Ceftriaxone
Topiramate or phenytoin
Phenytoin is on my Todo list as well, besides donepezil, both are sigma-1 agonists/modulators and have different additional mechanisms that might be helpful with the ME pathophysiology.

This is an excerpt of what I wrote Dr. Been.

A review of different allosteric modulators of Sig-1R has been done by Vavers et al. [14]. They list
Fenfluramine as another SSRI alternative to FVX. But they also list various anticonvulsant drugs, most
of which are experimental candidates, besides Phenytoin, an affordable and repurposed anti-seizure
anti-tachycardia drug that targets voltage-gated sodium channels and calcium channels [18, 19, 20,
21, 22]. Calcium and sodium channel overactivation participate in ME pathology [15, 16]. I expect this
finding to be transferable to LHS pathology. Seizures aren't uncommon among ME patients either [23].
Another concern of ME is neuropathic pain and fibromyalgia. Anti-seizure medications such as
Phenytoin are candidates for these kinds of pain where OTC analgesics do not work [24, 25].
Therefore, while FVX provides a multi-functional mechanism during the early phase of the SARS-CoV-
2 infection, Phenytoin might be the preferred alternative to provide a multi-functional mechanism to
LHS and ME with risks and side effects that can be managed better than serotonin-mediated ones.

The safety of the therapy could be further improved by reducing the dosage of Phenytoin since the
recommended dosage is meant for epilepsy patients who have significantly increased risks for
seizures when compared to ME or LHS.

Another Sig-1R agonist that is affordable and could be repurposed with a multi-functional mechanism
for ME and LHS pathology is the early Alzheimer's drug donepezil [26, 27]. Both ME and LHS are
associated with GPC, muscarinergic, cholinergic receptor antibodies [28, 29, 30]. Neurologically active
cholinesterase inhibitors have shown positive outcomes in ME [31]. The advantage of Donezepil is
that it combines these two mechanisms, namely Sig-1R agonism and cholinesterase inhibition. It
would be another viable alternative to FVX without the serotonin-mediated risks and side effects while
adding another mechanism.

Theoretically, Sig-1R agonism and positive allosteric modulation can also be combined if the doses
are reduced adequately. The appropriate dosage could be found by slowly increasing it while checking
for potential adverse effects. A dose-finding study could clarify this question but I don't expect a
generalizable dosage since I'm generally a supporter of patient-adjusted dosing.
  1. The IDO Metabolic Trap Hypothesis for the Etiology of ME/CFS (2019) [10.3390/diagnostics9030082]
  2. The Mechanism of Substrate Inhibition in Human Indoleamine 2,3-Dioxygenase (2012) [10.1021/ja208694g]
  3. Chronic COVID-19 Syndrome and Chronic Fatigue Syndrome (ME/CFS) following the first pandemic wave in Germany: a first analysis of a prospective observational study (2021) [10.1101/2021.02.06.21249256]
  4. Adolescent and Young Adult ME/CFS After Confirmed or Probable COVID-19 (2021) [10.3389/fmed.2021.668944]
  5. Fluvoxamine alleviates ER stress via induction of Sigma-1 receptor (2014) [10.1038/cddis.2014.301]
  6. Repurposing of CNS drugs to treat COVID-19 infection: targeting the sigma-1 receptor (2021) [10.1007/s00406-020-01231-x]
  7. Antibody-mediated platelet activation in COVID-19: A coincidence or a new mechanism of the dysregulated coagulation system? (2021) [10.1111/jth.15275]
  8. Serotonin is elevated in COVID-19-associated diarrhoea (2020) [10.1136/gutjnl-2020-323542]
  9. Thrombocytopathy and endotheliopathy: crucial contributors to COVID-19 thromboinflammation (2020) [10.1038/s41569-020-00469-1]
  10. Platelet Activating Immune Complexes Identified in COVID-19 Associated Coagulopathy (2020) [10.1101/2020.11.04.20226076]
  11. Serotonin syndrome in two COVID-19 patients treated with lopinavir/ritonavir (2020) [10.1016/j.jns.2020.116944]
  12. Drug repurposing of selective serotonin reuptake inhibitors: Could these drugs help fight COVID-19 and save lives? (2021) [10.1016/j.jocn.2021.03.010]
  13. COVID-19 Pathophysiology: Are Platelets and Serotonin Hiding in Plain Sight? (2021) [10.2139/ssrn.3800402]
  14. Allosteric Modulators of Sigma-1 Receptor: A Review (2019) [10.3389/fphar.2019.00223]
  15. Pathophysiology of skeletal muscle disturbances in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) (2021) [10.1186/s12967-021-02833-2]
  16. The symptoms of chronic fatigue syndrome are related to abnormal ion channel function (2000) [10.1054/mehy.1998.0822]
  17. SARS-CoV-2 organising pneumonia: ‘Has there been a widespread failure to identify and treat this prevalent condition in COVID-19?’ (2020) [10.1136/bmjresp-2020-000724]
  18. Mechanism of calcium channel inhibition by phenytoin: comparison with classical calcium channel antagonists (1985) [pmid: 2414431]
  19. Neuroprotection by Sodium Channel Blockade with Phenytoin in an Experimental Model of Glaucoma (2005) [10.1167/iovs.05-0618]
  20. Phenytoin: an old but effective antiarrhythmic agent for the suppression of ventricular tachycardia (2013) [10.5694/mja13.10224]
  21. Phenytoin differentially modulates the affinity of agonist and antagonist ligands for sigma 1 receptors of guinea pig brain (2005) [10.1002/syn.20103]
  22. Differences in the allosteric modulation by phenytoin of the binding properties of the sigma1 ligands [3H](+)-pentazocine and [3H]NE-100 (2006) [10.1002/syn.20230]
  23. An Etiological Model for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (2011) [10.4236/nm.2011.21003]
  24. Fibromyalgia as a Localized Non-Length-Dependent Small Fiber Neuropathy, Responding to Topical Phenytoin (2019) [10.23880/mjccs-16000213]
  25. Intravenous Infusion of Phenytoin Relieves Neuropathic Pain: A Randomized, Double-Blinded, Placebo-Controlled, Crossover Study (1999) [10.1213/00000539-199910000-00030]
  26. Activation of sigma-1 receptor chaperone in the treatment of neuropsychiatric diseases and its clinical implication (2015) [10.1016/j.jphs.2014.11.010]
  27. Efficacy of donepezil in early-stage Alzheimer disease: a randomized placebo-controlled trial (2004) [10.1001/archneur.61.12.1852]
  28. Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome (2016) [10.1016/j.bbi.2015.09.013]
  29. Functional autoantibodies against G-protein coupled receptors in patients with persistent Long-COVID-19 symptoms (2021) [10.1016/j.jtauto.2021.100100]
  30. Are nicotinic acetylcholine receptors coupled to G proteins? (2013) [10.1002/bies.201300082]
  31. Trial of a Selective Acetylcholinesterase Inhibitor, Galanthamine Hydrobromide, in the Treatment of Chronic Fatigue Syndrome (2011) [10.1300/J092v02n02_04]
 
Last edited: