Abilify- Stanford Clinic Patients

[leokitten]

I just skipped a dose of my 1.5 vraylar today to see if lower doses would help, but i feel like death today. not sure if its even worth trying to experiment with the dose because i was fairly stable on the 1.5 dose. I will give it another week and then go back (or hek, increase the dose).
ps good luck with the new bottle!

I read Vraylar is quite activating even at 1.5 mg, so some people take it only twice a week and with the very long half life it is effectively like taking a signif lower dose

 

[Frunobulax]

@Dude I’m also confused because my understanding of the D2 autoreceptor was that activation would result in lower dopamine release. I could be wrong but all these things need to be studied so that we know what is happening in patients that improve from Abilify.

This paper suggests that LDA could be able to restore sensitivity for dopamine receptors: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10561607/
So perhaps it's not the dopamine production after all. This would also explain why it works so well for some of us while it does nothing for others.

For context, Restless Legs is treated with dopamine agonists (parkinson drugs). A common side effect is augmentation, a desensibilization of dopamine receptors that appears to be semi-permanent and worsens the illness despite higher drug doses. (Drug studies sponsored by pharma claim it's reversible, but that's not the experience in clinical practice.) The paper above is a case study on 4 patients who augmented badly, and abilify was able to do wonders for 3 while the 4th still saw improvement.

Typically augmentation happens with drugs like pramipexol with affinity for the D3 receptor, but I believe Abilify modifies D3 and pramipexol works on D2 as well. Unfortunately I don't know anything about dopamine receptors.

But here's my story: I myself augmented in 2012-2013 on pramipexol, my RLS went from fairly mild to horrible and didn't return to anywhere near baseline in the 10 years since after coming off the evil stuff. I've had to take 20-25mg oxycodone ever since and this dose was a hard lower limit. Now, 5 weeks on abilify and now on .5mg/d, I reduced my Oxy for the 3rd time down to 5mg, and I'm still sleeping better than before. Amazing and totally unexpected.

 

[Frunobulax]

Apologies for the off-topic question.
My doctor suspected that since Abilify worked well, Wellbutrin should also be effective for me, which it wasn't. Lately, there have been increasing reports and medication studies focusing on acetylcholine receptors.
[...]

I looked into the potential effects of low acetylcholine levels, and surprisingly, it reads almost like ME/CFS symptoms. I wondered if dopamine also affects acetylcholine, and yes, dopamine D2 receptors can influence the release of acetylcholine in certain brain regions. What if this is a receptor issue? It's speculative, of course, just a hypothesis.

Wasn't there a recent paper from Scheibenbogen et al suggesting that anticholinergic effects may be responsible for ME/CFS symptoms?

As to receptors, I agree, see my previous post.

 

[Frunobulax]

Do we know this to be a fact from actual people's experience? I know the original paper from Stanford argued this but I don't trust that Bonilla quack.

Why do you call him a quack?

I know several people who reported hitting a sweet spot around 1mg/d. Going higher would only increase side effects.

 

[SlamDancin]

@Frunobulax I don’t know enough about him to weigh in about him being a quack but I do remember that that study had no placebo group. There were some other issues with it IIRC

 

[leokitten]

Why do you call him a quack?

I know several people who reported hitting a sweet spot around 1mg/d. Going higher would only increase side effects.

Bonilla would refuse to believe his patients telling him Abilify would stop working. This happens to most pwME

 

[Frunobulax]

@Frunobulax I don’t know enough about him to weigh in about him being a quack but I do remember that that study had no placebo group. There were some other issues with it IIRC

That's the norm for retrospective studies. They're considered weaker evidence, rightfully so, but it's quite common to have a retrospective study as first step to form conjectures, and then a placebo controlled, double blind study as followup. Nothing wrong about that, especially since the study is aware of these limitations and discusses them.

Bonilla would refuse to believe his patients telling him Abilify would stop working. This happens to most pwME

Huh, that's a red flag. Unfortunately not unusual for doctors who often have a tunnel vision on one treatment. Can you quantify "most"? Do you believe that the numbers in the study are overly optimistic?

My impression was that if it works at all, then there's at least a 50-50 chance that it will work for quite a while if you stick to the protocol (continue strict pacing and slowly increase exertion). So far I've heard more positive than negative experiences, counting people that I know in rl. But my sample size is small.

 

[leokitten]

That's the norm for retrospective studies. They're considered weaker evidence, rightfully so, but it's quite common to have a retrospective study as first step to form conjectures, and then a placebo controlled, double blind study as followup. Nothing wrong about that, especially since the study is aware of these limitations and discusses them.


Huh, that's a red flag. Unfortunately not unusual for doctors who often have a tunnel vision on one treatment. Can you quantify "most"? Do you believe that the numbers in the study are overly optimistic?

My impression was that if it works at all, then there's at least a 50-50 chance that it will work for quite a while if you stick to the protocol (continue strict pacing and slowly increase exertion). So far I've heard more positive than negative experiences, counting people that I know in rl. But my sample size is small.

It would be an earth shattering thing in the ME community if we found a drug that would work for 50% if they only aggressively paced for a few months even when feeling better. Others who are also on FBK and Discord LDA groups probably know better than me but I’m pretty confident that for the vast majority of pwME Abilify stops working. I’m the only one or one of a handful on this entire forum where LDA slowly loses efficacy but then starts to work again when I take a months long break. For pretty much everyone else it worked amazingly once and never worked again or it never worked at all.

 

[Frunobulax]

IDK, I'm more optimistic than you I guess. And the FB group has people taking Abilify for 5+ years. But that's not representative, one reason why I'm sceptic about all information coming from FB

Abilify is much more common in the US than here in EU, I had a very hard time getting it at all because all docs sh*t their pants about possible side effects and liability. (Which is a joke anyway because over here it's literally impossible to win a lawsuit against a doctor even with blatant malpractice.) Therefore the number of ME/CFS patients I know taking abilify is small, and nobody knows anything about that drug.

It's curious though. Dopamine agonists are well known from Restless Legs to lose efficiency over time (the afore mentioned augmentation), but for most patients it takes 1-10 years. And in general, the shorter the half-life and the higher the dose, the shorter the time until augmentation. So if dopamine is causal for the improvement, then I would expect that Abilify should work some years at least, given that it has a long half-life and is given at a low dose. If that's not the case, then this is a big question mark behind the assumption that dopamine (or sensibilization of dopamine receptors) is the reason for the improvement that some of us see.

 

[leokitten]

It's curious though. Dopamine agonists are well known from Restless Legs to lose efficiency over time (the afore mentioned augmentation), but for most patients it takes 1-10 years. And in general, the shorter the half-life and the higher the dose, the shorter the time until augmentation. So if dopamine is causal for the improvement, then I would expect that Abilify should work some years at least, given that it has a long half-life and is given at a low dose. If that's not the case, then this is a big question mark behind the assumption that dopamine (or sensibilization of dopamine receptors) is the reason for the improvement that some of us see.

Abilify doesn’t work at all like regular dopamine agonists. Also we have no real idea how Abilify helps, it also how powerful effects on the immune system, cellular metabolism, and hormones, so no one can currently say for sure it’s due to dopamine network modulation, but you are right if you were to pick one dopamine modulation would be the first choice.

 

[leokitten]

IDK, I'm more optimistic than you I guess. And the FB group has people taking Abilify for 5+ years. But that's not representative, one reason why I'm sceptic about all information coming from FB

Abilify is much more common in the US than here in EU, I had a very hard time getting it at all because all docs sh*t their pants about possible side effects and liability. (Which is a joke anyway because over here it's literally impossible to win a lawsuit against a doctor even with blatant malpractice.) Therefore the number of ME/CFS patients I know taking abilify is small, and nobody knows anything about that drug.

I definitely think every person with ME should at least try Abilify. The long-term side effect nonsense is a a bit of a joke, Abilify is prescribed not only for schizophrenia but also for depression and other illnesses. I personally think ME is severe and life changing enough that the risk-benefit is worth it if it will work for you. The effect on your life is worse than anyone with depression. You would know within two weeks of taking between 0.25-2 mg per day whether it works for you or not, so that’s very low risk to me. If it does work for you then you can take it from there an evaluate whether the very low risk of long term issues is worth the benefit.

 

[leokitten]

IDK, I'm more optimistic than you I guess. And the FB group has people taking Abilify for 5+ years. But that's not representative, one reason why I'm sceptic about all information coming from FB

Have you trialed Abilify? Sorry that I haven’t kept up

 

[Inez]

I recently tried 5-htp for a week and it has significantly worsened my ME. As LDA reduces serotonin could that be how it improves symptoms?

Has there been any exploration of the autoantibodies to 5-HT since this study?

https://pubmed.ncbi.nlm.nih.gov/23664637/

"The incidence of positive autoimmune activity against 5-HT was significantly higher (p<0.001) in ME/CFS (61.5%) than in patients with CF (13.9%) and controls (5.7%). ME/CFS patients with 5-HT autoimmune activity displayed higher TNFα, IL-1 and neopterin and increased IgA responses against LPS of commensal bacteria than those without 5-HT autoimmune activity. Anti-5-HT antibody positivity was significantly associated with increased scores on hyperalgesia, fatigue, neurocognitive and autonomic symptoms, sadness and a flu-like malaise."

 

[SlamDancin]

I don’t think Abilify’s effects on serotonin are similar to 5-htp. It activates some serotonin receptors and blocks others, and moderately inhibits the serotonin transporter like SSRIs.

 

[Inez]

I don’t think Abilify’s effects on serotonin are similar to 5-htp. It activates some serotonin receptors and blocks others, and moderately inhibits the serotonin transporter like SSRIs.

Right, they're not similar at all. I'm wondering if abilify helps exactly because it blocks some serotonin receptors.

 

[SlamDancin]

Doubt it but you could try Cyproheptadine it blocks all serotonin receptors

 

[Dude]

Maybe the problem is due to too low BH4 levels. Ron Davis is currently investigating the role of Bh4 in MECFS. https://studypages.com/s/study-to-i...h4-deficiency-in-mecfs-and-long-covid-525299/

Tetrahydrobiopterin (BH4) is an essential cofactor in the biosynthesis of the neurotransmitters dopamine and serotonin and in the conversion of phenylalanine to tyrosine.

BH4 acts as a cofactor for the enzyme tryptophan hydroxylase, which plays a key role in converting tryptophan to 5-hydroxytryptophan (5-HTP), which is then further metabolized to serotonin.

 

[Frunobulax]

Have you trialed Abilify? Sorry that I haven’t kept up

Yes, but I just started 5 weeks ago or so. Seeing a marked improvement so far at 0.5mg. I'm also cautiously optimistic because I could cut my RLS drugs in half, and I blame them at least for making my CFS worse, possibly for causing it. But we'll see what happens in a few months.

 

[Inez]

Doubt it but you could try Cyproheptadine it blocks all serotonin receptors

I'm going to try it. If anyone has tried it before I'd be interested to hear experiences

 

[leokitten]

Hi everyone I have a significant update - with the new bottle of Abilify I still need to take 2 mg to have a good effect! So this comes as a bit of shock/surprise to me, which means the very old bottle was still potent enough and the way my body has responded to it this third cycle is different than the first two cycles.

To summarize my experience again, the first time I took LDA I took 0.25 mg per day for two weeks and felt nothing until from one day to the next I pretty much went into remission, the effects were very strong, and I only needed 0.5-0.75 for months after. The second time I took 0.25 for only a week before the effects came on again strongly and suddenly and again only needed 0.25-0.75 for months after. Going higher than that never improved its effects.

This third cycle such a low starting dose did not work, I needed 2 mg per day to get symptom relief and the effects did not come on strongly, they creeped up more slowly and smoothly. LDA also felt less activating this time, I don’t have as much very early waking or restlessness side effects either. In addition, I also feel it’s effects are not persisting as long as the first two times (which was for months), after only one month now it feels like before on month 3 or 4, my ME symptoms are creeping back in. That being said I’ve done A LOT of exertion this last month I’ve been able to function well enough to go on a vacation and was able to drive, fly, and do enough physical activity on the vacation except exercise. I couldn’t go all out but really didn’t need to pace.

Though there is one major difference between my situation this time and the previous two times. Before I’d been on moclobemide 600 mg but this time I’ve been taking fluoxetine 60 mg per day. Could fluoxetine or any SSRI for that matter reduce Abilify’s effects or worse could this mean Abilify with each cycle is starting to not work? Ugh, I really don’t want to come off fluoxetine to test what’s going on it has a very long half life.