Amisulpride — A Multipurpose Drug for ME/CFS

[Hip]

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 personally found that very low-dose amisulpride also:

Reduces ME/CFS noise sensitivity symptoms
Greatly reduces ME/CFS irritability symptoms
Improves sociability
Treats mild psychosis symptoms
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, such as pain.

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 (third-generation antipsychotics) such as amisulpride (Solian) aripiprazole (Abilify) have been shown to benefit ME/CFS when taken in combination with an antidepressant — see this post. Amisulpride was the original third-generation antipsychotic. Ref: 1

A dopamine system stabilizer acts as an agonist of the dopamine receptors at low dopamine concentrations, but acts as an antagonist at high dopamine concentrations. So it boosts the dopamine system when dopamine is low, but puts the breaks on the system when dopamine is high. Refs: 1 2

My theory as to why dopamine stabilizer drugs are helpful for ME/CFS is here.


This paper indicates the two mechanisms of dopamine stabilization:

Partial agonists that display affinity for dopamine autoreceptors are potential stabilisers of dysregulated dopamine release in schizophrenia (Grunder et al, 2003).

However, it has been suggested that dopamine autoreceptor antagonists (sulpiride and amisulpride) also stabilise dopamine systems in schizophrenia by increasing dopamine release and selectively blocking D2 and D3 receptors in the limbic system (Kerwin, 2000).

Aripiprazole (Abilify) comes under the first mechanism, as it is a partial agonist with affinity for dopamine autoreceptors; and amisulpride comes under the second mechanism.



The response to amisulpride is also dose-level dependent:

At low doses, amisulpride blocks the dopamine autoreceptors. An autoreceptor is presynaptic regulatory feedback mechanism which controls how much of a neurotransmitter like dopamine is being released into the synapse (the junction between neurons). When you block the dopamine autoreceptors, it makes the neuron think there is not enough dopamine in the synapse, so more dopamine is released. In this way, blocking dopamine autoreceptors leads to more dopamine release.

But at high doses of amisulpride, then this drug starts to antagonize the postsynaptic dopamine receptor (the normal dopamine receptor), and at these higher doses the overall effect is dopamine antagonism. Refs: 1 2

This study says:

At low doses, amisulpride (100 mg/die or less) preferentially blocks presynaptic dopamine autoreceptors that control dopamine synthesis and release; whereas, at higher doses, it presents postsynaptic dopamine D2-receptor antagonism.

Aripiprazole behaves similarly at the presynaptic and postsynaptic dopamine receptors. This paper says:

There is evidence that aripiprazole functions as both a presynaptic D2 agonist and post synaptic D2 antagonist. Presynaptic D2 autoreceptors may play a vital role in the ability of aripiprazole to act as a DA system stabilizer, but at higher doses (such as the ones used to treat schizophrenia), aripiprazole also has a significant binding affinity at post synaptic D2 receptors.

Aripiprazole's dopamine stabilization is described here:

At high dopamine concentrations, aripiprazole lowers dopamine neuronal firing, while at low concentrations it increases dopamine firing. At the time, this mechanism of action was called ‘dopamine stabilization’ because a single drug could increase or decrease neuronal firing as needed.

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 ).



There are serious side effects that can result from taking antipsychotics, such as extrapyramidal symptoms like tardive dyskinesia. And developing type 2 diabetes is a risk too. But on the low-dose protocols of amisulpride or Abilify, the risks of these side effects are very much less. Refs: here and here.




BUYING AMISULPRIDE:
Amisulpride can be bought prescription-free from any of the following pharmacies:
InHouse, United Pharmacies, United Pharmacies UK, International Drug Mart, GoldPharma, 4RNX, 4NRX UK, Pharmacy Geoff, Buy Pharma, ClearSky Pharmacy, Over-the-Counter.

Other prescription-free pharmacies where amisulpride can be bought listed in this post.

Spoiler: More Info on the Unique Advantages of Amisulpride (Click Here)

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

 

[Hip]

Amisulpride, the Wonder Drug from France!

The following text was copied from here.

Amisulpride is a new antipsychotic drug that was invented in France. It is so new, it is still in the USA’s final testing stage for release here, but can still be obtained now legally from Europe.

Amisulpride is a very safe drug with few, if no side effects, and can be used for three different purposes.

NORMAL DOSE PROTOCOL:
In normal doses, 400mg-1200mg, it is used for symptoms that include and excess and/or disruption in cognition and emotional functions.

LOW DOSE PROTOCOL:
In lower doses, 50mg-200mg, it is used for symptoms that include a diminution or loss of normal cognitive and/or emotional functions.

VERY LOW DOSE PROTOCOL:
In even lower doses, 12.5mg-200mg, it is used for minor depression, attention-deficit/hyperactivity, and emotional imbalances.

It was discovered by accident that amisulpride, originally created as an antipsychotic drug for schizophrenia, has the antidepressant effect when taken in minuscule doses as compared to what was originally intended. The drug appears to have an opposite effect depending on if small or larger doses are taken.

Originally designed to be taken at 400mg to 800mg a day, when you take Amisulpride instead at just 12.5mg to 100mg a day combats LOW MOOD, CONSTANT NEGATIVE THOUGHTS, SOCIAL ANXIETY, ANHEDONIA (inability to experience pleasure), and FATIGUE. These are the symptoms of atypical depression or dysthymic disorder, which is a mild but continuous form of depression. The symptoms are characterized by blahness, lack of motivation, lack of interest, and social withdrawal. While combating these problems in an amazing way that no other drug seems to do, the low, low dose also makes amisulpride almost completely free of side effects, so it is tolerated by more people, more often than other anti-depressants.

In a day, or a week or two, depending on the person, on amisulpride one feels renewed interest, renewed motivation, social comfort, more confident, and less emotional anxiety. You’ll notice a very strange blunting of ONLY the emotional triggers that seem to be the ones you’d want to get rid of. It’s difficult to explain, but a strange yet wonderful experience!

It feels as if you’ve been freed of mental issues that have held you back from doing things you wish you would be doing.

Each person that has responded to the effect is immediately amazed. Others who see the transformation of their friends have been equally amazed.

Because amisulpride has an opposite effect at higher doses, for depressive treatment, you must prepare yourself to cut back on the dose if you feel any negative effects like sedation. Rather than immediately giving up, be aware that this is exactly what it’s supposed to do, and it simply means that your body is so sensitive that a lower dose is the appropriate one for you.

Most drugs don’t have the opposite effect the moment the dose is too high, so this unique quality should be known before you start on your journey.

Every person is different and it takes a unique milligram dose for each person that could be anywhere between as little as 12.5mg to 100mg so you need to understand that it’s not a bad thing if you don’t feel the correct effect; you simply adjust the dose and continue to find the exact amount that is right for you. DON’T GIVE UP!

Specifically, a the low doses, Amisulpride is a “selective dopamine antagonist” which stimulates specific types of dopamine receptors (D2 and D3) on their presynaptic side. D2/D3 limbic system pathways are thought to be involved in regulating mood, anxiety and motivation. Unlike many other medications, it exclusively acts in the mesolimbic brain, which is unusual, because this is the site where emotional mood states and memory storage and retrieval takes place in your brain. This is great because it doesn’t unnecessarily stimulate other dopaminergic receptors elsewhere in the brain, so locomotion and general attention/arousal systems are largely bypassed, eliminating sleep disturbances, anxiety exacerbations, the jitters, and scattered and/or hyper-attentiveness. For this specific purpose, it is used in very low doses (12.5-100mg/day).

Since it was designed to be used at much higher doses, there are few side effects at these low doses. Keep in mind it may take up to two weeks to feel any effects from amisulpride, so try it for at least 2 weeks! It seems to have a very unusual ability to tone down a person’s unwanted emotional outbursts in a very precise clean way, while preserving the drive to accomplish important matters in their life. Strangely enough, it actually seems to shut down the part of the brain that spends time worrying about other people’s problems or going in circles about personal emotional issues. The emotional spin cycle simply disappears!

It’s such a wonderful feeling to have emotional baggage simply lifted from you within the course of 2 weeks without therapy!

At doses above 400mg, amisulpride stimulates the same dopamine receptors but on their postsynaptic side. At this dosage, amisulpride treats disorganized symptoms including thought disorder, confusion, disorientation, and memory problems.

This drug was invented in France, and is still in Phase III FDA testing here in the USA, therefore it is only available by mailorder from Europe. It is not a scheduled substance and is legal to import in personal use quantities. Amisulpride works in a novel way, it doesn’t affect seratonin at all, it affects only dopamine, so it works when SSRI antidepressants don’t. Specifically, it increases the dopamine in the synaptic cleft of the D2-D3 receptors in the limbic system and to a lesser extent the striatum. It improves mood, concentration, energy, and sense of pleasure while decreasing social anxieties.


More info

Amisulpride: A Review of its Clinical Potential in Dysthymia
Amisulpride in medium-term treatment of dysthymia


Amisulpride dosage

One half 50mg tablet (25mg) once a day (use a razor blade to cut pills in half).

The effect is generally seen in 7-14 days.

If you feel sedation, cut back to 12.5mg/day ¼ tablet.

Since amisulpride has the OPPOSITE effect at higher doses, you should realize a dose too high will cause an effect opposite of what is desired.

Alternatively, if you feel no effect at 25mg/day, you can raise the dosage by 25mg increments to 100mg day maximum to get the best effect for you.

Wait at least a week after each 25mg increment; keep in mind 12.5mg-50mg should be sufficient.

Not available in the USA.

 

[adreno]

One problem with the drug is that prolactin levels often go through the roof. Did you experience this?

 

[Hip]

One problem with the drug is that prolactin levels often go through the roof. Did you experience this?

I haven't developed any "man boobs" (gynecomastia), which I believe is a symptom of high prolactin in men. Though I do notice my libido is significantly reduced on days when I take amisulpride — and reduced libido can result from high prolactin.

I usually take a very low 12.5 mg daily dose of amisulpride; and every week or two, I take a break from amisulpride for a couple of days. So at this very low dose, perhaps I am not raising my prolactin levels too much.

Even so, I wish I could find a workaround to prevent the low libido induced by amisulpride.

 

[adreno]

Pantethine should be an inhibitor of prolactin, by the way. I use it with pregnenolone and DHEA. I haven't done any tests, but libido is good.

 

[Hip]

Pantethine should be an inhibitor of prolactin, by the way. I use it with pregnenolone and DHEA. I haven't done any tests, but libido is good.

I might try that. I read that pantethine may have some neuroprotective effects, plus it seems to treat fatty liver, which I have.

Vitamin B6, vitamin E and SAM-e are good prolactin inhibitors, according to this article.

 

[FunkOdyssey]

Doesn't look like there is much hope for resolving sexual sides, aside from a switch to aripiprazole, which may or may not provide any of the same benefits:

J Sex Marital Ther. 2012;38(3):281-301. doi: 10.1080/0092623X.2011.606883.
Strategies for the treatment of antipsychotic-induced sexual dysfunction and/or hyperprolactinemia among patients of the schizophrenia spectrum: a review.

Nunes LV, Moreira HC, Razzouk D, Nunes SO, Mari Jde J.
Source

Department of Psychiatry, Universidade Estadual de Londrina, Paraná, Brazil.
Abstract

There is limited evidence for the management of sexual dysfunction and/or hyperprolactinemia resulting from use of antipsychotics in patients with schizophrenia and spectrum. The aim of this study was to review and describe the strategies for the treatment of antipsychotic-induced sexual dysfunctions and/or hyperprolactinemia. The research was carried out through Medline/PubMed, Cochrane, Lilacs, Embase, and PsycINFO, and it included open labels or randomized clinical trials. The authors found 31 studies: 25 open-label noncontrolled studies and 6 randomized controlled clinical trials. The randomized, double-blind controlled studies that were conducted with adjunctive treatment that showed improvement of sexual dysfunction and/or decrease of prolactin levels were sildenafil and aripiprazole. The medication selegiline and cyproheptadine did not improve sexual function. The switch to quetiapine was demonstrated in 2 randomized controlled studies: 1 showed improvement in the primary outcome and the other did not. This reviewed data have suggested that further well-designed randomized controlled trials are needed to provide evidence for the effects of different strategies to manage sexual dysfunction and/or hyperprolactinaemia resulting from antipsychotics. These trials are necessary in order to have a better compliance and reduce the distress among patients with schizophrenia.
PMID:
22533871

 

[FunkOdyssey]

Actually, it looks like maybe you can add aripiprazole to another antipsychotic and its partial d2 agonism is able to keep prolactin down. It isn't clear how that would affect the benefits of amisulpride though, seems to me if it can overpower the d2 antagonism of other antipsychotics at the pituitary, it would be able to do it throughout the brain:

J Psychopharmacol. 2008 May;22(3):244-53. doi: 10.1177/0269881107082901.
Change in sexual dysfunction with aripiprazole: a switching or add-on study.

Mir A, Shivakumar K, Williamson RJ, McAllister V, O'Keane V, Aitchison KJ.
Source

COAST Team (Croydon Early Intervention in Psychosis Service), Westways Resource Centre, Croydon, UK.
Abstract

Sexual dysfunction and raised prolactin are common adverse effects of many anti-psychotics. Aripiprazole is an atypical anti-psychotic associated with a reduction in prolactin level in anti-psychotic-induced hyperprolactinemia. Our hypothesis was that switching from another anti-psychotic to aripiprazole would be associated with a reduction in sexual dysfunction. An open label switch to aripiprazole was offered to 27 subjects with inadequate therapeutic response or intolerance to another anti-psychotic, who were followed up for 26 weeks. Serial clinical ratings included the Anti-psychotic Non-Neurological Side-Effects Rating Scale (ANNSERS), and the Sexual Functioning Questionnaire. Our primary analysis point was week 12. In both sexes, there was a significant reduction in prolactin by week 12 (P = 0.003), accompanied by a significant improvement in libido (P = 0.028). In males, both erectile and ejaculatory difficulties were also significantly reduced (P = 0.04 and P = 0.017, respectively). In females, menstrual dysfunction was also significantly reduced at week 12 (P = 0.04). By week 26, the changes in all of the above remained significant, and were accompanied by a significant increase in satisfaction in overall sexual functioning (P = 0.007), despite the fact that 54.5% of subjects at were also taking their original antipsychotic. There was also a significant decrease in the total ANNSERS score (P < 0.001) and a significant improvement in all other measures of psychopathology (PANSS, CGI-S/I, GAF-S/D, and QoL). We conclude that switching to aripiprazole or the addition of aripiprazole to another antipsychotic regime is associated with a reduction in sexual dysfunction.
PMID:
18308789

 

[Hip]

Actually, it looks like maybe you can add aripiprazole to another antipsychotic and its partial d2 agonism is able to keep prolactin down. It isn't clear how that would affect the benefits of amisulpride though, seems to me if it can overpower the d2 antagonism of other antipsychotics at the pituitary, it would be able to do it throughout the brain:

That is very interesting. So, if I understand correctly, the reason for excess prolactin release by amisulpride (and other anti-psychotic drugs) is because it blocks the dopamine D2 receptors in the pituitary gland.

And aripiprazole has the reverse effect, as it stimulates the pituitary dopamine D2 receptors.


One of the things I find the most useful with very low dose amisulpride is that this drug noticeably reduces my irritability and annoyance symptoms.

Irritability seems to be a fairly common symptom in ME/CFS (and in autism). On bad days, I find myself irritable with everything: people, places, opinions — anything that moves! Irritability is a very unpleasant symptom — especially because you always have the urge to express your irritability and annoyance to people; and yet you know that your irritability is generally not warranted; it's just a ME/CFS mental symptom that makes you that way; so you have to try to bite your lip and suppress expressing your irritability.

Interestingly, it seems that aripiprazole is good for treating irritability in autism, with doses of 2 mg and higher, so I wonder if aripiprazole may work for ME/CFS irritability too. Ref: 1.


EDIT: looks like aripiprazole does not reverse amisulpride-induced hyperprolactinaemia.

 

[Hip]

By the way, Funk, would you have any idea of how aripiprazole treats irritability, in terms of its actions at receptors. I would like to understand the neurochemistry of irritability.

Amisulpride not known for its ability to treat irritability (or at least I have not seen any literature on this), but I have personally found that amisulpride reduces irritability symptoms. It makes me a little more tolerant of things, and also makes me more tolerant of sound and noise.

 

[heapsreal]

Pantethine should be an inhibitor of prolactin, by the way. I use it with pregnenolone and DHEA. I haven't done any tests, but libido is good.

Sorry to go off topic but adreno have u found preg and dhea increase prolactin?

 

[adreno]

Pantethine is a precursor to cysteamine, which depletes prolactin:

Prog Neuropsychopharmacol Biol Psychiatry. 1990;14(6):835-62.
Preclinical and clinical studies with cysteamine and pantethine related to the central nervous system.

Vécsei L, Widerlöv E.
Source

Department of Psychiatry and Neurochemistry, University of Lund, Sweden.
Abstract

1. Cysteamine is formed by degradation of coenzyme A (CoA) and causes somatostatin (SS), prolactin and noradrenaline depletion in the brain and peripheral tissues. 2. Cysteamine influences several behavioral processes, like active and passive avoidance behavior, open-field activity, kindled seizures, pain perception and SS-induced barrel rotation. 3. Cysteamine has several established (cystinosis, radioprotection, acetaminophen poisoning) and theoretical (Huntington's disease, prolactin-secreting adenomas) indications in clinical practice. 4. Pantethine is a naturally occurring compound which is metabolized to cysteamine. 5. Pantethine depletes SS, prolactin and noradrenaline with lower efficacy compared to that of cysteamine. 6. Pantethine is well tolerated by patients and has been suggested to treatment of atherosclerosis. The other possible clinical indications (alcoholism, Parkinson's disease, instead of cysteamine) are discussed.
PMID: 2277850

 

[adreno]

It works in rats:

Pantethine, a cysteamine precursor, depletes immunoreactive somatostatin and prolactin in the rat.

The depletion of plasma prolactin by pantethine in oestrogen-primed hyperprolactinaemic rats.


Whether this would reverse the effects of antipsychotics, I don't know.

 

[adreno]

Sorry to go off topic but adreno have u found preg and dhea increase prolactin?

They do from the studies I have seen, IIRC. They also gave me tingling nipples in the beginning, but it went away (with pantethine, I presume)

 

[Pachequín Bombín]

Hi Hip. I'm also taking amisulpride for my ADHD, but I haven't seen any result that just somnolence since three weeks ago Does it help for concentration? I'm taking 50 mg now, but as you say, I must cut back to 25 mg. What is the best dosage? 25 or 12.5 mg? Does it depend on my weight? Thank you so much.

 

[Hip]

Hi Hip. I'm also taking amisulpride for my ADHD, but I haven't seen any result that just somnolence since three weeks ago Does it help for concentration? I'm taking 50 mg now, but as you say, I must cut back to 25 mg. What is the best dosage? 25 or 12.5 mg? Does it depend on my weight? Thank you so much.

I usually take 12.5 mg daily. What I personally find is that taking 25 mg gives a stronger effect, but I get the impression this higher dose reduces my motivation and reduces my focus on doing things. So this is why I usually stick with 12.5 mg.

 

[Hip]

I just found this thread on Phoenix Rising on using the above-mentioed atypical antipsychotic drug Abilify (aripiprazole) for treating ME/CFS:

Abilify and energy

I have just ordered some Abilify, and will compare its benefits to those of amisulpride.

I have a good opinion of atypical antipsychotics as a treatment for ME/CFS (based so far on my experience with amisulpride) and others might find these drugs useful.

General Note:
Don't be concerned about using an antipsychotic drug for ME/CFS. Atypical antipsychotics are not just used for psychosis and schizophrenia: atypical antipsychotics are also used off-label for many other conditions, such as: depression, ADHD, anxiety disorder, bipolar disorder, PTSD, OCD, dementia, etc (reference: here).

Atypical antipsychotic drugs alter levels of neurotransmitters in various part of the brain; the only thing that really matters is whether the changes these drugs make to neurotransmitter levels translates to a benefit for ME/CFS patients; it is of no importance at all that these drugs are labelled as antipsychotics — that is just part of their function.

In any case, the doses of these drugs used for ME/CFS treatment are much, much smaller than the dose used for psychosis and schizophrenia.

 

[adreno]

Even atypical antipsychotics potentially have some very nasty side effects (diabetes, tardive dyskinesia etc), so just be careful. Personally I won't touch them, not even Abilify. I also believe that modulating the glutamate/GABA balance is more effective than blocking dopamine.

 

[Hip]

Even atypical antipsychotics potentially have some very nasty side effects (diabetes, tardive dyskinesia etc), so just be careful. Personally I won't touch them, not even Abilify. I also believe that modulating the glutamate/GABA balance is more effective than blocking dopamine.

Point taken. I would definitely say that to help minimize the possibility of side effects, take the lowest does you feel is offering benefits. In my case, my daily dose of just 12.5 mg of amisulpride is very much lower than the 400 to 800 mg doses used for treating schizophrenia and psychosis. So I hope that this makes the risk of side effects much lower. I have been taking amisulpride for a year now, and have seen no real side effects.


Amisulpride Side Effects: Assessment of Risks

I cannot find any data on amisulpride, but found some info on a similar drugs risperidone and clozapine, which are also from the atypical anti-psychotic drug class. Risperidone is used to treat ME/CFS (risperidone one of Dr Jay Goldstein's ME/CFS treatments that sometimes brings major remission from ME/CFS).

It says here that the risk of developing diabetes mellitus from the atypical anti-psychotic drug risperidone is 0.05% (= 1 in 2000 patients), and the risk from the atypical anti-psychotic drug clozapine is 2.03% (= 1 in 50 patients). Though these statistics I think apply to people taking the full dose of these drugs, not the very low dose regimen that I use.

In the case of the very low dose amisulpride that I am taking, my dose of 12.5 mg is almost 100 times smaller than the highest 1200 mg dose of amisulpride used for schizophrenia, so presumably that very low dose significantly lowers the diabetes risk.


Also, in this very low dose protocol, amisulpride works in the opposite way to its full dose regimen. In the very low dose protocol, amisulpride actually boosts the dopaminergic system, whereas in the full dose regimen, amisulpride inhibits the dopaminergic system (which antipsychotics usually do). Amisulpride is in effect a different drug when used at the very low dose protocol.

It is the dopaminergic inhibition caused by anti-psychotics that is linked to triggering the extrapyramidal symptoms like tardive dyskinesia; so the fact that in my very low dose amisulpride protocol I get dopaminergic boosting rather than inhibition perhaps means that this very low dose protocol will not be less subject to the risks of extrapyramidal symptoms.

But even low-dose amisulpride can sometimes lead to tardive dyskinesia: see this study of a patient who was give low-dose amisulpride (100 mg daily) as an antidepressant.

 

[Hip]

One of my main reasons for taking amisulpride is because I find it increases my social motivations; that is to say, amisulpride increases my desires to engage in social activity.

I find that it it not just the fatigue of ME/CFS that draws you away from socializing; there seems to be an increased need for peace and solitude in ME/CFS, with too much social activity perturbing the mind. I sometimes feel my mind has been almost "mentally raped" after too much social activity. I think this feeling of being "mentally raped" is actually caused by a weakened "mental firewall" — that is to say, a weakness in the mind's sensory stimuli filter, which allows stimuli to enter into consciousness, when they really should have been filtered out. This weakened "mental firewall" I think is also the reason for noise sensitivity in ME/CFS.

I am pretty sure this "mental firewall" itself is located in the reticular formation of the brainstem. The reticular formation's functions are known to include filtering out irrelevant or repetitive stimuli, so that the rest of the mind is not overloaded with unnecessary information. So for example, for a normal healthy person, if they hear a car alarm go off in their street, at first this noise rouses their consciousness attention, but then they soon forget about it, and after a few minutes, it does not enter consciousness anymore. This filtering out is called habituation, and is the reticular formation's "firewall" springing into action, and blocking irrelevant, repetitive stimuli from reaching consciousness and thereby overloading the brain.

However, I find that in ME/CFS, repetitive noises such as car alarms are constantly aggravating, because you do not seem to habituate to the noise, and so the noise continually deeply penetrates into your conscious mind and becomes unpleasant; this repetitive noise is not properly filtered out by your "mental firewall".

I suspect a weakened reticular formation "firewall" is the norm in ME/CFS, and this leads to the feeling of being overwhelmed or "mentally raped" when exposed to too many stimuli, as you tend to get in hectic social situations. These stimuli are penetrating deep into the mind, whereas they should have been stopped by the "firewall", stopped by the brain's bouncer at the door: the reticular formation.

Anyway, what I have found is that amisulpride seems to make this "mental firewall" stronger, so that you are more able to cope with the maelstrom of social environments; and with amisulpride I find that sounds and other sensory stimuli are not so mentally intrusive.