Abilify- Stanford Clinic Patients

[JES]

It's very common for drugs/supplements to stop working with ME/CFS, that's just the way it is. Unless you are treating the root cause (which I don't think Abilify does) there's always a chance of relapse, but it doesn't mean it necessarily will happen. In any case, improvements like these are remarkable from severe patients and hopefully it will help researchers to get one step closer in understanding this disease.

I predicted months ago in post above that Abilify would likely stop working at some point. This isn't because I have some special insight, it's just the way it seems to be with ME/CFS treatments.

My own experience with new drugs is that there tends to be a honeymoon period, which for me is even shorter, a couple of days to a week. After the initial improvement, you either fall back into the "trap" or often times, you even end up slightly worse than baseline. I have also noticed the reverse effect. When I attempt to reduce dosage of, say, an antidepressant, I again start to feel better. This keeps repeating until I'm off the drug, at which point baseline symptoms return.

If I understood correctly, Martin was feeling best at the point when he was still in transition of increasing the dosage, which sounds exactly like the honeymoon effect. Since this happens with so many drugs in ME/CFS, I don't think there is necessarily anything unique about Abilify causing this. Similar tolerance issues seem common in for example epilepsy, one paper here describes some interesting hypotheses.

I really think the problem boils down to figuring out a way to understand and avoid this effect, but unfortunately I have yet to have any practical success doing so.

 

[hmnr asg]

It seems @Martin aka paused||M.E. is trying a new dopinaminergic medication ? (sorry Martin, I creep on your instagram )

As for findind another similar medication to abilify, there is amisulpride which was shown by @Hip to be useful at low doses:

https://forums.phoenixrising.me/threads/amisulpride-a-multipurpose-drug-for-me-cfs.20964/

Also, lets keep in mind that Martin is a single data point. I am another one and so far my experiment with abilify has been good. 20% improvement initially and now after two months im down to about 10%, but its still something! (the caveat being that I also take cymbalta, now sure if that does anything).

I wonder if i quit abilify and restart again at the lower dose I will get the initial improvements back. I was doing better at 1mg than at the 2mg. I should get the solution as @leokitten suggested.

 

[leokitten]

Interesting review of research on the impact of inflammation on the dopamine system as well as a theoretical model and computational method trying to connect it all.

Could be a hypothesis as to why Abilify and dopaminergic agents have some partial efficacy in ME, even if it is temporary (so only a part of the ME symptom story, not for example what are the cause(s) of the chronic inflammation).

https://forums.phoenixrising.me/thr...treadway-mt-et-al-trends-cogn-sci-2019.82158/

 

[Martin aka paused||M.E.]

It seems @Martin aka paused||M.E. is trying a new dopinaminergic medication ? (sorry Martin, I creep on your instagram )

As for findind another similar medication to abilify, there is amisulpride which was shown by @Hip to be useful at low doses:

https://forums.phoenixrising.me/threads/amisulpride-a-multipurpose-drug-for-me-cfs.20964/

Also, lets keep in mind that Martin is a single data point. I am another one and so far my experiment with abilify has been good. 20% improvement initially and now after two months im down to about 10%, but its still something! (the caveat being that I also take cymbalta, now sure if that does anything).

I wonder if i quit abilify and restart again at the lower dose I will get the initial improvements back. I was doing better at 1mg than at the 2mg. I should get the solution as @leokitten suggested.

Im planning to try sth

 

[Martin aka paused||M.E.]

Interesting review of research on the impact of inflammation on the dopamine system as well as a theoretical model and computational method trying to connect it all.

Could be a hypothesis as to why Abilify and dopaminergic agents have some partial efficacy in ME, even if it is temporary (so only a part of the ME symptom story, not for example what are the cause(s) of the chronic inflammation).

https://forums.phoenixrising.me/thr...treadway-mt-et-al-trends-cogn-sci-2019.82158/

I read from a Patient who takes it on/off and it works ... so maybe it’s not only temporarily but you have two withdraw it always after a few months

 

[Martin aka paused||M.E.]

I predicted months ago in post above that Abilify would likely stop working at some point. This isn't because I have some special insight, it's just the way it seems to be with ME/CFS treatments.

My own experience with new drugs is that there tends to be a honeymoon period, which for me is even shorter, a couple of days to a week. After the initial improvement, you either fall back into the "trap" or often times, you even end up slightly worse than baseline. I have also noticed the reverse effect. When I attempt to reduce dosage of, say, an antidepressant, I again start to feel better. This keeps repeating until I'm off the drug, at which point baseline symptoms return.

If I understood correctly, Martin was feeling best at the point when he was still in transition of increasing the dosage, which sounds exactly like the honeymoon effect. Since this happens with so many drugs in ME/CFS, I don't think there is necessarily anything unique about Abilify causing this. Similar tolerance issues seem common in for example epilepsy, one paper here describes some interesting hypotheses.

I really think the problem boils down to figuring out a way to understand and avoid this effect, but unfortunately I have yet to have any practical success doing so.

So many theories about myself, why aren’t you guys don’t just asking? No it’s wrong, I felt best right before it stopped working from one day to another. That was when I took 4 mg for three months

 

[leokitten]

So many theories about myself, why aren’t you guys don’t just asking? No it’s wrong, I felt best right before it stopped working from one day to another. That was when I took 4 mg for three months

Martin I had a question I forgot to ask and this reminded me. What was behind your decision to go fairly quickly up to the “high for ME” dose of 4 mg/day?

 

[Martin aka paused||M.E.]

Martin I had a question I forgot to ask and this reminded me. What was behind your decision to go fairly quickly up to the “high for ME” dose of 4 mg/day?

impatience

 

[leokitten]

impatience

In hindsight, and given your direct experience taking and feeling this drug, do you feel it would make a difference if you had started at a really low initial dose (0.25 mg/day), stayed there for a long while for your body and ME to adjust, and then only very slowly over months stepped up the dose by a 0.25 mg increment as needed? Such as stepping up only if benefits plateaued etc.

 

[Martin aka paused||M.E.]

In hindsight, and given your direct experience taking and feeling this drug, do you feel it would make a difference if you had started at a really low initial dose (0.25 mg/day), stayed there for a long while for your body and ME to adjust, and then only very slowly over months stepped up the dose by a 0.25 mg increment as needed? Such as stepping up only if benefits plateaued etc.

No

 

[leokitten]

I read from a Patient who takes it on/off and it works ... so maybe it’s not only temporarily but you have two withdraw it always after a few months

Yeah definitely give it a go to try, as I think you were already planning to, but now I think after longer washout period

 

[Yuno]

I probably wrote it unclear.
I dont have constant excitations and orgasms. And abilify is not the cause of the problem. It does just increase the risk of having one. The last three weeks I havent had one at all. But it was extremely exhausting to control absolutely each tought all the time. I have many ice pads beside my bed to cool me down if I start feeling excitment. That works to some degree. But it makes me mentally ill!

On the other hand Abilify works quite well physically. I wouldnt be able to use my smartphone, watch tv or use a spoon otherwise...sooo it's worth the higher risk of having a crash for me.

Cheers
Marco

Hi,
you said that you got severe braindamage from taking tenofovir,if I got that right. How did that happen or what exactly happened? This is very interesting to me, as i was planning on trialing tenofovir. thanks

 

[Yuno]

My question was if anyone heard about its effect in ME. Of course this is a dangerous drug

olanzapine did not help me. But i just trialed it for 5 days or so. made me feel tired and stoned and have me a migraine. but that being said,abilify does not help me. already 0,25 ml gives me a lot of energy, but I crash heavily on the next day. to me it feels more like doping than real energy. but as we know: everybody is different. lol

 

[Studi]

Hi,
you said that you got severe braindamage from taking tenofovir,if I got that right. How did that happen or what exactly happened? This is very interesting to me, as i was planning on trialing tenofovir. thanks

I took tenofovir for about 5 weeks( slowly ingreasing the dose) when I start having orgasms just by thinking of a woman. The damage remains after stopping the drug.
I found a study that says that the mousebrain changed during treatment with tenofovir....But I haven't heard it from an other human so far.....

 

[S-VV]

I think we need a low dose selective presynaptic dopamine agonist (ideally with a short half-life), to achieve a steady state of increased synaptic dopamine, the same principle as in low dose naltrexone really. Antagonism of presynaptic receptor will eventually lead to up-regulation and decreased dopamine output.

 

[S-VV]

Coincidentally, the need to de-sensitize Dopamine auto receptors was realised by the late Dr. Goldstein more than 20 years ago:

"I am ineluctably drawn to the conclusion that DA receptors are dysfunctional in neurosomatic disorders. The primary dysfunction appears to be in the NAc DA autoreceptor, which may be D2/D3 in type (Shafer RA, Levant B, 1998)."

"It pains me to write this, but the situation is more complicated than I have just described. Presynaptic DA may be totally depleted or the mechanism by which stored DA moves to the edge of the presynaptic membrane where it is secreted (the “ready-releasable pool”) may be dysfunctional.

Neither of these explanations can account for the rapid symptom fluctua- tions commonly seen in neurosomatic disorders and certainly could not demonstrate why increasing DA transmitters can cause a relapse. These phenomena can be interpreted, however, as stemming from hypersensitivity of the DA autoreceptor.

What is an autoreceptor? The presynaptic neuron, which secretes most transmitters, must have a mechanism to sense how much transmitter it has secreted (i.e., how much is in the synapse). How autoreceptors themselves are regulated is imperfectly understood, but calcium ions are thought to be involved. Calcium is perhaps the most important intracellular regulating el- ement.

If the DA autoreceptor is hypersensitive, small amounts of secreted DA will result in a marked decrease of further DA secretion. Such a scenario may be applicable to patients with neurosomatic disorders. An ideal drug, therefore, would block the DA autoreceptor and “fool” the neuron so that a low DA concentration is sensed in the surrounding environment. "

"In a hyperglutamatergic state, as I have postulated for neurosomatic disorders, the D2 and other autoreceptors would be hypersensitive, limiting DA secretion in the phasic phase which is more relevant to human behavior. Indeed,"

 

[Martin aka paused||M.E.]

Coincidentally, the need to de-sensitize Dopamine auto receptors was realised by the late Dr. Goldstein more than 20 years ago:

"I am ineluctably drawn to the conclusion that DA receptors are dysfunctional in neurosomatic disorders. The primary dysfunction appears to be in the NAc DA autoreceptor, which may be D2/D3 in type (Shafer RA, Levant B, 1998)."

"It pains me to write this, but the situation is more complicated than I have just described. Presynaptic DA may be totally depleted or the mechanism by which stored DA moves to the edge of the presynaptic membrane where it is secreted (the “ready-releasable pool”) may be dysfunctional.

Neither of these explanations can account for the rapid symptom fluctua- tions commonly seen in neurosomatic disorders and certainly could not demonstrate why increasing DA transmitters can cause a relapse. These phenomena can be interpreted, however, as stemming from hypersensitivity of the DA autoreceptor.

What is an autoreceptor? The presynaptic neuron, which secretes most transmitters, must have a mechanism to sense how much transmitter it has secreted (i.e., how much is in the synapse). How autoreceptors themselves are regulated is imperfectly understood, but calcium ions are thought to be involved. Calcium is perhaps the most important intracellular regulating el- ement.

If the DA autoreceptor is hypersensitive, small amounts of secreted DA will result in a marked decrease of further DA secretion. Such a scenario may be applicable to patients with neurosomatic disorders. An ideal drug, therefore, would block the DA autoreceptor and “fool” the neuron so that a low DA concentration is sensed in the surrounding environment. "

"In a hyperglutamatergic state, as I have postulated for neurosomatic disorders, the D2 and other autoreceptors would be hypersensitive, limiting DA secretion in the phasic phase which is more relevant to human behavior. Indeed,"

Brain fog deluxe... are there any medical interventions ?

 

[S-VV]

Brain fog deluxe... are there any medical interventions ?

No idea man. Maybe a low dose dopamine antagonist (1st gen anti-psychotics) will lead to long term up regulation of post-synaptic receptors... Its worth discussing with your doctor if he understands the reasoning behind low dose naltrexone

 

[leokitten]

"In a hyperglutamatergic state, as I have postulated for neurosomatic disorders, the D2 and other autoreceptors would be hypersensitive, limiting DA secretion in the phasic phase which is more relevant to human behavior. Indeed,"

Why not directly treat the hyperglutamatergic state instead? I’ve always wondered if nitromemantine would have efficacy in ME. I wish it could be sourced to try.

I used to take memantine, but it has a nasty side effect with me where it worsened my ME vestibular and balance symptoms, so it made me even more dizzy to the point of nausea. Even when lying down my brain didn’t know which way was up anymore and it was like I was rolling or rocking in space even though I was still. Memantine is known to cause vestibular issues in some people.

 

[Martin aka paused||M.E.]

No idea man. Maybe a low dose dopamine antagonist (1st gen anti-psychotics) will lead to long term up regulation of post-synaptic receptors... Its worth discussing with your doctor if he understands the reasoning behind low dose naltrexone

Thinking of taking an dopamine agonist like Pramipexole... helped at least one patient here