Hello everyone. I know that this will not sound believable at first, but I'm pleased to announce that I have potentially found a treatment approach for a significant subset of CFS patients. It's been a long 16 years of suffering with this debilitating disease — now my time has come to continue living, instead of simply existing. Perhaps your time has also come?
TL;DR Low dose Ziprasidone via 5-HT2C antagonism may help a significant subset of CFS sufferers and may be even better than low dose Aripiprazole.
*Please note: This is my personal experience and theory. Always consult with healthcare providers before making any treatment decisions.*
## Who might this help? Contraindications?
This approach is potentially viable for a specific subset of CFS patients who meet the following criteria:
1) low (or no) emotions
2) a schizoid-type personality (see: 'schizoid personality disorder')
3) non-existent anxiety
4) anhedonia
5) low/no libido
6) low blood pressure
7) difficulty gaining weight
Perhaps the group of people is even wider, but for now this seems like plausible criteria given my hypothesis.
## The rationale
Luckily I'm in a position where I could easily test any medication I wanted on myself as a guinea pig (*don't do this — I had specific circumstances that made this possible*), while having sufficient financial resources to finance my health experiments.
After years of study and trial-and-error, I've come to the conclusion that my chronic fatigue was due to insufficient noradrenaline and dopamine. However, I've tried all legal and illegal stimulants that exist, as well as many, many other prescription medications. The stimulants in particular are "correct" in the sense that they target catecholamine release, yet they're, unfortunately, a band-aid at best, just stop working after a short time, and quickly make things even worse. So I was stuck knowing that my body either is incapable of producing catecholamines or simply refuses to excrete them — even when appropriate, i.e., in situations of physiological stress. I ruled out that my biochemical pathways for catecholamine production are defective via whole genome sequencing. Furthermore, I have no Parkinson-like symptoms, which means that in theory, baseline dopamine is there. It's simply not being properly excreted under mental and physical load.
Another piece of the puzzle was that any kind of medication which increased my serotonin seemed to make things much, much worse. This includes SSRIs and SNRIs in particular. This made me suspect that I perhaps have too much serotonin.
Indeed, there are even studies you can find online showing that people with CFS have higher serotonin. There's even a thing called the "central fatigue or serotonin hypothesis of ME/CFS".
Yes. Indeed. And from here on — after weeks of research — I finally stumbled over the 5-HT2C serotonin receptor: This is the holy grail of CFS in my (not so humble) opinion.
It turns out that this receptor — when activated — increases GABA in key parts of the brain. This GABA in turn acts as a brake pedal on endogenous catecholamine release. Could this be it?
Well, it turns out that medications targeting 5-HT2C even have their own name: "Norepinephrine–dopamine disinhibitor (NDDI or NDD)". Have a look at the Wikipedia page: it's extremely short. This mechanism has NOT been sufficiently studied, and there are only very few medications that potentially classify as a NDDI:
Agomelatine, Aripiprazole, Buspirone, Cyproheptadin, Filbanserine, Fluoxetine, Mianserin, Mirtazapin, Olanzapine, Quetiapine, Vilazodone, Ziprasidone
The big issue with most of these medications is that they — in addition to targeting 5-HT2C — either:
1) strongly antagonize the histamine receptor H1, leading to tiredness and fatigue
2) act as a strong agonist on the melatonin receptors, leading to tiredness and fatigue; or
3) act as a strong SSRI, increasing the issue at hand — namely high serotonin.
Interestingly, Aripiprazole shows up in the above list. The informed readers will know about the existing LDA (low dose abilify/Aripiprazole) treatment for CFS that seems to work wonders for some people. So it seems like we might have something significant here... Anyways, I've found something even better than Aripiprazole, namely **Ziprasidone**. Interestingly, it's also an atypical antipsychotic — like Aripiprazole. Bookmark this tab right now, because this may be a historic moment you're witnessing. Ziprasidone has an extremely good receptor binding profile. It acts as a serotonin 5-HT2A and 5-HT2C antagonist with very high affinity. Taking this in low doses gives an extremely targeted effect without the nasty histamine receptor antagonism. It also works as a partial agonist on some 5-HT1 receptors, which may also contribute to its positive effects.
As an added bonus, I combine this with yohimbine-hcl, giving me a slightly better noradrenaline/dopamine ratio via alpha2 antagonism. This combination is the perfect NDDI medication and is what Mirtazapine would like to be / should have always been.
## My CFS treatment plan
5-20 mg Zeldox® (Ziprasidone) liquid per day
5-15 mg Yohimbine-hcl per day
*Note: These are psychiatric medications that require medical supervision. The typical dosage for treating schizophrenia is 120+mg/day, so these are very low doses, but still require careful monitoring.*
The liquid form of Ziprasidone called Zeldox - similar to Abilify - is optimal for titrating the dosage. The yohimbine is optional, but good especially if you have issues with vasodilation/ low blood pressure. They complement each other very nicely.
I can tell you from first hand experience that I feel exactly how I felt before getting CFS. I feel human again and I'm quite sure, that many of you could benefit from low dose Ziprasidone.
*This is my personal experience and may not work for everyone. CFS likely has multiple subtypes with different underlying mechanisms. Please work with knowledgeable healthcare providers if you're considering this approach.*
TL;DR Low dose Ziprasidone via 5-HT2C antagonism may help a significant subset of CFS sufferers and may be even better than low dose Aripiprazole.
*Please note: This is my personal experience and theory. Always consult with healthcare providers before making any treatment decisions.*
## Who might this help? Contraindications?
This approach is potentially viable for a specific subset of CFS patients who meet the following criteria:
1) low (or no) emotions
2) a schizoid-type personality (see: 'schizoid personality disorder')
3) non-existent anxiety
4) anhedonia
5) low/no libido
6) low blood pressure
7) difficulty gaining weight
Perhaps the group of people is even wider, but for now this seems like plausible criteria given my hypothesis.
## The rationale
Luckily I'm in a position where I could easily test any medication I wanted on myself as a guinea pig (*don't do this — I had specific circumstances that made this possible*), while having sufficient financial resources to finance my health experiments.
After years of study and trial-and-error, I've come to the conclusion that my chronic fatigue was due to insufficient noradrenaline and dopamine. However, I've tried all legal and illegal stimulants that exist, as well as many, many other prescription medications. The stimulants in particular are "correct" in the sense that they target catecholamine release, yet they're, unfortunately, a band-aid at best, just stop working after a short time, and quickly make things even worse. So I was stuck knowing that my body either is incapable of producing catecholamines or simply refuses to excrete them — even when appropriate, i.e., in situations of physiological stress. I ruled out that my biochemical pathways for catecholamine production are defective via whole genome sequencing. Furthermore, I have no Parkinson-like symptoms, which means that in theory, baseline dopamine is there. It's simply not being properly excreted under mental and physical load.
Another piece of the puzzle was that any kind of medication which increased my serotonin seemed to make things much, much worse. This includes SSRIs and SNRIs in particular. This made me suspect that I perhaps have too much serotonin.
Indeed, there are even studies you can find online showing that people with CFS have higher serotonin. There's even a thing called the "central fatigue or serotonin hypothesis of ME/CFS".
Yes. Indeed. And from here on — after weeks of research — I finally stumbled over the 5-HT2C serotonin receptor: This is the holy grail of CFS in my (not so humble) opinion.
It turns out that this receptor — when activated — increases GABA in key parts of the brain. This GABA in turn acts as a brake pedal on endogenous catecholamine release. Could this be it?
Well, it turns out that medications targeting 5-HT2C even have their own name: "Norepinephrine–dopamine disinhibitor (NDDI or NDD)". Have a look at the Wikipedia page: it's extremely short. This mechanism has NOT been sufficiently studied, and there are only very few medications that potentially classify as a NDDI:
Agomelatine, Aripiprazole, Buspirone, Cyproheptadin, Filbanserine, Fluoxetine, Mianserin, Mirtazapin, Olanzapine, Quetiapine, Vilazodone, Ziprasidone
The big issue with most of these medications is that they — in addition to targeting 5-HT2C — either:
1) strongly antagonize the histamine receptor H1, leading to tiredness and fatigue
2) act as a strong agonist on the melatonin receptors, leading to tiredness and fatigue; or
3) act as a strong SSRI, increasing the issue at hand — namely high serotonin.
Interestingly, Aripiprazole shows up in the above list. The informed readers will know about the existing LDA (low dose abilify/Aripiprazole) treatment for CFS that seems to work wonders for some people. So it seems like we might have something significant here... Anyways, I've found something even better than Aripiprazole, namely **Ziprasidone**. Interestingly, it's also an atypical antipsychotic — like Aripiprazole. Bookmark this tab right now, because this may be a historic moment you're witnessing. Ziprasidone has an extremely good receptor binding profile. It acts as a serotonin 5-HT2A and 5-HT2C antagonist with very high affinity. Taking this in low doses gives an extremely targeted effect without the nasty histamine receptor antagonism. It also works as a partial agonist on some 5-HT1 receptors, which may also contribute to its positive effects.
As an added bonus, I combine this with yohimbine-hcl, giving me a slightly better noradrenaline/dopamine ratio via alpha2 antagonism. This combination is the perfect NDDI medication and is what Mirtazapine would like to be / should have always been.
## My CFS treatment plan
5-20 mg Zeldox® (Ziprasidone) liquid per day
5-15 mg Yohimbine-hcl per day
*Note: These are psychiatric medications that require medical supervision. The typical dosage for treating schizophrenia is 120+mg/day, so these are very low doses, but still require careful monitoring.*
The liquid form of Ziprasidone called Zeldox - similar to Abilify - is optimal for titrating the dosage. The yohimbine is optional, but good especially if you have issues with vasodilation/ low blood pressure. They complement each other very nicely.
I can tell you from first hand experience that I feel exactly how I felt before getting CFS. I feel human again and I'm quite sure, that many of you could benefit from low dose Ziprasidone.
*This is my personal experience and may not work for everyone. CFS likely has multiple subtypes with different underlying mechanisms. Please work with knowledgeable healthcare providers if you're considering this approach.*
