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Amisulpride — A Multipurpose Drug for ME/CFS

Hip

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@Stretched You'd have to check with a drugs interactions checker to see if there are any concerns mixing those drugs.
 
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I have been taking very low doses (12.5 mg daily) of the drug amisulpride for around a year now, and I have found this drug quite helpful for a number of mental and cognitive symptoms that arise in ME/CFS and its comorbid conditions like depression and anxiety disorder.

At very low doses, amisulpride is know to act as an:

Antidepressant treatment
Anti-anhedonia treatment
Anti-anxiety treatment


I have also found that very low dose amisulpride also:

Reduces ME/CFS noise sensitivity symptoms
Greatly reduces ME/CFS irritability symptoms
Improves sociability
Treats anxiety psychosis symptoms (anxiety psychosis from anxiety disorder)
Improves attention deficit-hyperactivity disorder (ADHD)


I have all the above conditions, and so I found amisulpride particularly useful.

This small scale study of the benefits of amisulpride for ME/CFS found that 25 mg of this drug taken twice daily reduced fatigue and somatic complaints.

Amisulpride is not licensed in the US, but it can be obtained from the usual overseas suppliers. I believe the smallest available size of amisulpride tablets is 50 mg, so you will need to cut these 50 mg tablets in half or in quarters if you want to take the very lowest doses of 25 mg and 12.5 mg.

I find 12.5 mg is a good dose for me; if I go up to 25 mg, it seems to make me a bit torpid and unmotivated.



UPDATE: Dopamine system stabilization drugs such as amisulpride and aripiprazole have been shown to benefit ME/CFS when taken in combination with an antidepressant — see this post.


Note that amisulpride is not the only antipsychotic that may show benefit in ME/CFS: quetiapine (Seroquel) is also used in ME/CFS and fibromyalgia for treating pain and improving sleep (as well as helping depression ).



BUYING AMISULPRIDE:
Amisulpride can be bought prescription-free from any of the following pharmacies:
1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 .

Amisulpride can also be bought in powder form at TrueLife Research.

Amisulpride : A forgotten "Old-School" AntiPsychotic with A Superior Anti-Depressant Profile & Unique Mechanism of Action (Little to no Side Effects)

Amisulpride certainly doesn't carry the wide array of pharmacological actions that most "familiar" or "Atypical Antipsychotics" do, but that doesn't make it any less potent (1).

AMISULPRIDE HAS FAR LESS SIDE-EFFECTS

One distinguishable trait of amisulpride is that lower doses seem to only, or mostly block the dopamine D2S (autoreceptors) (2) - which leads to an actual enhancement in dopamine release (3).

Most of the usual antipsychotics we hear about, e.g risperidone, thorazine and Haldol — all have very potent dual action dopamine receptor blockade (4). This leads to many more side-effects, including incidences of depression and high rates of drug-induced tardive dyskinesia (5).

Additionally, most anti-psychotic drugs have extremely potent alpha-1-adrenergic receptor blockade (6) (7), amisulpride lacks this property, as well as the usual anti histamine property of anti-psychotics (8) — which means AmiSulpride is very unlikely to cause any form of sedation (9).

Usually, the anti-histamine properties of other anti-psychotic drugs combined with the alpha-1-blockade — acts as a one-two punch in knocking the patient out cold.... frequently we hear about some of the affected even drooling on themselves or just completely incoherent and lethargic the following day (10)!

While some medical professionals consider this a benefit in hostile or unpredictable patients, I would find it much less than ideal for someone who wants to maintain somewhat of a normal life, not incapacitated but with symptoms controlled (11).

Besides lack of side-effects, or at least lack of sedation, amisulpride has one very notable effect that sets it apart from other drugs in its class — its anti-depressant effects are VERY FAST ACTING, very potent — and generally yield little to no negative endocrine effects (12).

The mechanism of action is totally unique, amisulpride binds to the serotonin 5-HT(7) with 11.5 nanomolar (ki/nm) affinity - this includes in human subjects (14).

It antagonizes the action of serotonin at this receptor — resulting in an anti-depressant effect that cannot only augment other anti-depressants — but can be much more effective alone than many anti-depressants (15).

The additional benefits of 5-HT(7) antagonism are that it will reduce overstimulation and anxiety - as well as treat depression - and lower cortisol levels as well (16).

Because many depressed patients exhibit HPAA (hypothalamic-pituitary-adrenal-axis) dysfunction — and often have elevated cortisol — this unique mechanism of action may benefit the hormonal balance of depressed patients (17), unlike SSRIs which tend to increase stress hormones (18) and oppose other beneficial neurotransmitters such as GABA, dopamine and others (19)!

Thus, in summary...

Amisulpride has the following benefits / advantages over other drugs aiming to do the same.
  • A cortisol reduction, instead of increase.
  • Enhances dopamine at lower doses.
  • Little to no sedation, drowsiness, dyskinesia, tremors , punding or other disturbing side-effects.
  • Doesn't interfere with cognitive function or vigilance.
  • Treats depression quickly , and effectively.
  • May improve anxiety symptoms as well.


Source: TrueLife Research
Thanks. I can't see that (m)any primary ME-CFS symptoms are being redressed by this drug. Seems like it's better suited to treat other disorders.
 

Stretched

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FWIW, I am an Amisulpride advocate, having followed @Hip's analysis and having similar symptoms.

It does the same for me as above, but I use it in 50mg units once a day in am. (I mistakenly bought the
only size this supplier had, 400mg, and 1/8's are the smallest 'slices' w/o powdering the pill, but divides fine
with a standard, ubiquitous plastic pill slicer.)

With a favorable side effect, it allows me to walk away from Sertraline without titration (take it or leave it), and has a similar effect with clonazepam, which I have taken for 30 years, minimally. I do wonder if there is an
inherent withdrawal potential w/Amis since it is has such noticeable efficacy? No need at present to withdraw - only if something 'non-redundant' falls off...:confused:
In all candor I have to report stopping Amisulpride. This past Christmas, 2018, I picked up a case of tremors, as in hands shaking. In reviewing meds it showed this as a possible side effect of antipsychotics. Coincidentally, in the same time frame my peripheral neuropathy in my feet flared into severe pain. I don’t know if any of this is connected to the underlying neurological nature of MECFS, casual or causal. I immediately stopped Amisulpride and am scheduled to see a neurologist soon for further evaluation.
 

Hip

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I can't see that (m)any primary ME-CFS symptoms are being redressed by this drug.
The study showed very low dose amisulpride substantially reduced ME/CFS fatigue and somatic complaints like pain (I've altered the first post to make this clearer).

I also found it reduced the ME/CFS sound sensitivity of ME/CFS, which is a common symptom. And it helped with anxiety and depression, which around 1 in 3 ME/CFS patients suffer from as a comorbid condition. And I found it worked wonders for irritability, which is a listed ME/CFS symptom in some ME/CFS classifications (this is not surprising, as the irritability of autism is treated with antipsychotics).


But even at very low doses, this is still an antipsychotic drug, so you would want to familiarize yourself with the major side effects of antipsychotics can cause before considering this drug.
 

stefanosstef

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In all candor I have to report stopping Amisulpride. This past Christmas, 2018, I picked up a case of tremors, as in hands shaking. In reviewing meds it showed this as a possible side effect of antipsychotics. Coincidentally, in the same time frame my peripheral neuropathy in my feet flared into severe pain. I don’t know if any of this is connected to the underlying neurological nature of MECFS, casual or causal. I immediately stopped Amisulpride and am scheduled to see a neurologist soon for further evaluation.
Would you mind sharing what happened eventually?Was your case of tremors caused by amisulpride?
 

Stretched

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Would you mind sharing what happened eventually?Was your case of tremors caused by amisulpride?
I’ve been seeing a neurologist since then as Peripheral Neuropathy in my feet began about that time. I was worried about Parkinsons Disease but he said likely not PD after some testing. It looked to him like ‘Essential tremors,’ one of about 10 common types (see Google). Further, he opined that they were most often caused by ingestion of other medicines. Since they still come and go with emotional stress I’m not sure he’s correct. He didn’t seem too concerned with narrowing down specific rxs. FWIW, my ongoing rx’s include Ambien, Zoloft, and several heart medications. IMO, the cause could be Ambien, Or another cause altogether, :( related to the neurology of MECFS, with which he is familiar. IAE, I never went back to Amisulpride since it is known to have
tremors as a side effect. It’s worrisome and uncomfortable, especially when flared! I hope this helps.
 

stefanosstef

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I’ve been seeing a neurologist since then as Peripheral Neuropathy in my feet began about that time. I was worried about Parkinsons Disease but he said likely not PD after some testing. It looked to him like ‘Essential tremors,’ one of about 10 common types (see Google). Further, he opined that they were most often caused by ingestion of other medicines. Since they still come and go with emotional stress I’m not sure he’s correct. He didn’t seem too concerned with narrowing down specific rxs. FWIW, my ongoing rx’s include Ambien, Zoloft, and several heart medications. IMO, the cause could be Ambien, Or another cause altogether, :( related to the neurology of MECFS, with which he is familiar. IAE, I never went back to Amisulpride since it is known to have
tremors as a side effect. It’s worrisome and uncomfortable, especially when flared! I hope this helps.
So the tremors started while you were taking amisulpride and you still have them today, so it is quite possible that they were caused by it.the positive side of this possibility is that you reacted quickly and stopped this from progressing.
 

Stretched

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So the tremors started while you were taking amisulpride and you still have them today, so it is quite possible that they were caused by it.the positive side of this possibility is that you reacted quickly and stopped this from progressing.
Possibly, but a key point in my mind is they will cycle without Amisulpride again entering the loop. Actually, they seem to emerge at times of increased stress or anxiety. Some of the time minimal, towards unnoticeable. Do I
think Amisulpride is the etiology? A couple of years using it might have been a catalyst and opened the gate,
so to speak on the peripheral neuropathy? Or, vice versa :confused: It’s not tested.
 
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I noticed no one mentioned this before but if something like a 'tremor' develops from taking a drug classified as antipsychotic, it is not a 'tremor' unfortunately, it's something called 'tardive dyskinesia' . It's permanent. Good thing you stopped taking it fast. If you search videos on youtube you'll see, it could have been much worse then a tremor, had you not stopped taking it.

It's the reason I stay away from any and all 'antipsychotics'.
 

Stretched

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Geez, TD looks awful! Some shakiness still comes and goes, re above. I’m wondering if taking Zoloft for 30+ years has contributed? I’ve read over the years that its efficacy is questionable, maybe not worth taking. However, stopping its use completely is difficult. The residual feelings make it just not worth withdrawing.
 

choochoo

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In all candor I have to report stopping Amisulpride. This past Christmas, 2018, I picked up a case of tremors, as in hands shaking. In reviewing meds it showed this as a possible side effect of antipsychotics. Coincidentally, in the same time frame my peripheral neuropathy in my feet flared into severe pain. I don’t know if any of this is connected to the underlying neurological nature of MECFS, casual or causal. I immediately stopped Amisulpride and am scheduled to see a neurologist soon for further evaluation.
Hi, may I ask, did your level of health change positive or negative after ceasing Amisulpride?
 

Rvanson

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Geez, TD looks awful! Some shakiness still comes and goes, re above. I’m wondering if taking Zoloft for 30+ years has contributed? I’ve read over the years that its efficacy is questionable, maybe not worth taking. However, stopping its use completely is difficult. The residual feelings make it just not worth withdrawing.
Zoloft is an SSRI antidepressant. I've found that most of the SSRI medications simply numb one out, or other such things. The MAOI antidepressants seem to work much better and without side effects like post SSRI loss of libido, which can be permanent like TD with the anti-psychotics. They are not used much anymore, as the young psychiatrists are scared of the so-called "Cheese Effect" they read about and trust in the newer drugs.
 

choochoo

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In all candor I have to report stopping Amisulpride. This past Christmas, 2018, I picked up a case of tremors, as in hands shaking. In reviewing meds it showed this as a possible side effect of antipsychotics. Coincidentally, in the same time frame my peripheral neuropathy in my feet flared into severe pain. I don’t know if any of this is connected to the underlying neurological nature of MECFS, casual or causal. I immediately stopped Amisulpride and am scheduled to see a neurologist soon for further evaluation.

Hi if you don't mind me asking, did you ever reduce your dose from the 50mg of amisulpride?
 
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Zoloft is an SSRI antidepressant. I've found that most of the SSRI medications simply numb one out, or other such things. The MAOI antidepressants seem to work much better and without side effects like post SSRI loss of libido, which can be permanent like TD with the anti-psychotics. They are not used much anymore, as the young psychiatrists are scared of the so-called "Cheese Effect" they read about and trust in the newer drugs.
Those are just excuses, older drug manufactures don't get paid anymore as the patent expired and generic forms became available. $$ is only in drugs that still have a valid patent, hence the doctors also get a % from newer drugs vs no % from the older ones.

If one had a great doctor, such doctor would even prescribe drugs that aren't manufactured anymore, with such a prescription you'd go to a specialized lab that synthetize these, made to order.
 

choochoo

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@Hip

Can you let us know how amisulpride helps with PEM?

I notice you extol the mental benefefits but you mention very little about PEM?

Do you find it improves PEM? If yes, in what way and by what degree?
 

choochoo

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Thanks for prompt reply?

This is a surprise. Because most people ive communicated with who seem to be improving claim more energy and shorter PEM.

Have you got more energy and stamina or are things just the same?

Whilst on this subject are you aware of anybody ( or have you? ) who has tried L-dopa ?
 

Hip

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Have you got more energy and stamina or are things just the same?
My symptoms which amisulpride improved are listed in the first post. This drug worked quite well for sound sensitivity and irritability, I found.

I did not notice any effects on energy or stamina, though a study found amisulpride may improve these (see 1st post).

I have not tried L-dopa.