Aripiprazole - Abilify

I had the exact same experience as you with keto. Such a dramatic improvement it felt like an almost total remission in the beginning. Most symptoms just melted away within 2-3 days of starting it. It was amazing, like my brain and body did a full reboot and were clear again, it was almost euphoric.

I didn’t realize this could be a possible part of the story as to why it did this, thank you.

 

@Sid I agree for the most part

But I believe these examples like the ketogenic diet and drugs like Abilify, which cause such a fast and dramatic improvement in more than a handful of people, are a window into ME pathophysiology.

I don’t believe these treatments just give a completely false sense of improvement or energy. I also don’t think these treatments cause improvements by simply raising catecholamines or signaling.

Take for example stimulants as a treatment for ME. That is what stimulants do. Many of us have tried them to combat symptoms and for me they did not feel at all like the ketogenic diet did. With stimulants, I felt all my ME symptoms the entire time underneath this false sense of energy and pain reduction and they truly didn’t increase exertion capacity before any PEM like keto did, I felt the PEM underneath but could more easily ignore it and push through until the crash.

When I restart the ketogenic diet it still gives me some significant improvements, it’s just the amount of work and exertion required to follow the protocol day in and day out to get into deep enough ketosis to get that improvement isn’t worth it anymore. But it still is doing something.

Part of the story of the drivers for a number of ME symptoms seem to be coming from sources positively affected by these treatments, whether it be dysregulation of monoamine neurotransmitter levels or signaling, neuroinflammation, dysregulation of neuroendocrine function, immune dysfunction (modulated by these treatments), etc.

 

Yeah. We can't paint these treatments with too broad a brush. While there are some commonalities like altering relevant neurotransmitters, aripiprazole is obviously much more selective in what you're trying to target. Something like keto on the other hand results in profound shifts in energy metabolism you can't get from a drug. Stimulants are a very broad category. Some of that icky, jacked up feeling of fake energy (while your symptoms are still there) you describe can be attributed to a drug that's more noradrenergic. This is a good thing for some types of depression and ADHD but not so good for us. Obviously when we examine the symptom profile of ME/CFS we see it's more of an issue of dopaminergic signalling, esp. in the basal ganglia.

 

It is worth having a careful look at the figures from the open label rituximab study I appended to my testimony for the NICE committee. Placebo response in ME can be huge. It can produce 'recovery' in a good proportion. There is no doubt about that.

If there is any point inS4ME at all it is pointing out that personal accounts of improvement on things like Abilify are of no interest unless someone has done a proper trial.

 

Many of the things we talk about on these forums are pretty pointless when it comes to improving our condition, doesn’t mean it not worth mentioning or pointing out testimonials and anecdotal reports. Regarding treatments, its especially worth mentioning because there are no worthwhile clinical trials even in the works. The only two we had go through phase III in decades were ampligen and rituximab, and most people aren’t too happy to have to wait decades more for others when we’ve had our entire lives robbed from us at way too young an age.

If we didn’t have people pointing out pointless things like antivirals and the like, then maybe there wouldn’t have been the subset of people who saw those reports, took the treatment, and greatly improved or went into remission. Yes we don’t know for certain if it was a placebo effect or if they were going to get better anyway, but does it really matter? Most treatments haven’t harmed most people. We all know this risk, but information is value and no information is dispair. It’s like saying playing the lottery is pointless. Chances are slim but it’s actually not.

 

I'm sorry to hear that. Important caveats though are:
- Abilify is a serotonergic drug as much as a dopaminergic drug;
- Even within the subclass of atypical antipsychotics, Abilify is atypical in that it acts as a partial agonist at D2, D3, and D4 receptors. This means it can correct high as well as low dopaminergic tone - low dopamine is suspected to be an issue in pwME. Abilify is thought to be a partial agonist at 5HT1A, 5HT2C and 5HT7 receptors, too. Only cariprazine has a similar-ish binding profile.

Buproprion is first and foremost a dopamine reuptake inhibitor, so its mechanism of action is completely different. Apples and oranges, really.

Which is not to say Abilify is immune to tachyphylaxis. Reading experiences on PR and here on s4me, it seems that when Abilify works for a patient, it remains effective for a number of months before true tolerance sets in, perhaps giving us scope to cycle the drug and stretch its effectiveness.

 

Thank you. You've put it much better than I ever could.

 

You sound like you're saying that ME is psychological and we just need to believe that we've taken a drug that works.

 

I think @Jonathan Edwards is right that I am probably being a bit overzealous when I said that there isn’t much placebo effect with ME patients.

It can exist, but so many of us have tried countless drugs, supplement protocols, and other treatments over the years and none have shown any effect whatsoever, no placebo no nothing, except when out of nowhere one treatment temporarily does cause a very dramatic and immediate effect over most symptoms for a couple months or so (in my case the ketogenic diet).

We also know it wasn’t due to some disease fluctuation because we were declining steadily for years and the fluctuations were only very minor steady for many months at a time. It’s hard to believe that that was due, even in part, to placebo effect.

 

This is a bit harsh, I think. By a proper trial, I assume you mean a RCT trial?

1) Personal accounts are valuable because they can point researchers in a direction so that they can conduct controlled trials!!

2) The overwhelming emphasis and energy on this forum is on "combating" gaslighting from physicians/researchers who say that MECFS patients have a psycho illness and not an medical illness. Isn't not gaslighting to state that a patient is not improving on a med because the med has not undergone a controlled trial?

3) Endpoints matter. For the 2 main meds that worked for me over the past 5 years, Valtrex and Abilify, if the end point was 6 months, there would probably be no difference between treatment and control, due to tachyphlaxis (poop out). If you measured at one or two months, then there would likely be a treatment effect. Knowing that there is an effect at one or two months, but not at 6 months or a year is still valuable data. Why? Because someone might be able to figure out a way to extend the efficacy of the drugs using an ancillary med.

4) There is a problem on other forums with people making claims about B vitamin methylation cycles, ozone, moon walking, yada, yada etc., helping them. This is unfortunate, and I assume that this was one reason for the split of the forums. But that doesn't mean you should ignore all claims of efficacy that occurred for meds trialed outside of a controlled trial.

5) FWIW I took rituximab and noted no improvement, but I did note a very notable and non-lasting improvement on Valtrex and Abilify.

6) I don't understand why there was a large placebo effect in the rituximab trial, but I worry that it may have poisoned the well for the UNCONTROLLED Norwegian cyclophosphamide trial, which had pretty spectacular treatment effects. I worry that patients and researchers lost faith in the UNCONTROLLED cyclo study because of the ritux study placebo effects. My point here is that the cyclo trial results shouldn't be discarded because it wasn't controlled.

 

It should be easy enough to do an RCT of this. Widely available drug, no travel to infusion centre necessary unlike in the rituximab trial etc.

@J.G I didn’t say the two drugs had the same mechanism of action. I was discussing dopaminergic interventions (including diet) more broadly.

Years ago when when the damage from SSRIs became evident and they started heavily promoting bupropion instead for depression there were quite a few anecdotal reports floating about it in our community. There’s been a heavy push in recent years to augment antidepressants with SGA especially aripiprazole. Some years ago the drug of the hour was low dose naltrexone so it seemed for a while like everybody was on it. Whatever is the latest fad in psychiatry trickles down to us since mainstream medicine believes that’s what’s wrong with us. Often ME/CFS patients are sold these psychotropics under the guise of improving sleep or pain or “reducing brain inflammation”.

 

I think it's used in bi-polar (type 2 bi-polar or some such)
Who is the Jonathan you refer to?

 

OMF/Stanford are planning a placebo-controlled trial on low-dose Abilify. And yeah, let's hope we can finally get some more RCT trials going on drugs for ME/CFS. Current lack of RCT evidence for ME/CFS treatments is depressing since the issue isn't just lack of evidence but that nothing has even been attempted.

 

@Sid I know, I know. My point is that all dopaminergic drugs are not equal, and your friend's experience with bupropion can therefore not necessarily be extrapolated into a warning about Abilify. It's also worth noting that the present interest in Abilify is coming from the exact opposite direction of the "latest fad in psychiatry". Rather, it comes from the serotonergic / dopaminergic implications of the metabolic trap theory, plus Abilify's proven capacity to improve the condition of our community's most famous patient. I understand that we are cautious and perhaps scarred by years of psychiatry's forcing neurodrugs on us, but that's not a reason to assume upfront that Abilify is but another symptom-masking generic that cannot offer improvements long-term.

 

I've heard that OMF plan to do a (Abilify) trial - anyone know anything about this?

 

Another account of Abilify on Reddit. I won't post anymore of these, but this one references an improvement in functional dyspepsia and occured several years ago:

 

Forgive my scepticism, but if that ends up being the case, it would be, to my knowledge, the first known instance of a psychiatric drug being disease-modifying in a true sense, in any condition. They all mask the symptoms. Some would argue that long-term pharmacotherapy with psychotropic drugs actually makes the underlying disease process worse for some people and I'm not even talking about the (potentially disfiguring) side effects. Over the decades of increasing use of these medicines, relapse rates in various psychiatric conditions and the need to use ever more medications (polypharmacy) have increased.

The metabolic trap hypothesis is speculation by bench scientists who have no clinical experience with psychotropic drugs. The fact that the community's most famous patient is improving is great news but let's not ignore the fact that he is or was also on a steroid.

If the metabolic trap exists then I would need to see people being pushed out of it by using aripiprazole and/or other drugs. What instead we are seeing is people relapsing if they get off the drug (which suggests that there are no long-term improvements, only symptom masking, i.e. the opposite of what the metabolic trap would predict) or relapsing while on the drug (tachyphylaxis). And that's the most generous interpretation assuming it's not placebo.

 

Hmm. Abilify does not eliminate trapped cells' elevated tryptophan content, so it cannot push a patient out of the trap. Abilify also does nothing about kynurenine pathway inhibition in trapped cells. But, if I read the hypothesis correctly, it predicts that secondary effects on TPH1/2 will cause serotonergic dysregulation, and also that tryptophanic inhibitory knock-on effects may occur on dopamine synthesis. As a partial agonist at certain receptors Abilify should - theoretically - counter both this dopamine understimulation and serotonin under/overstimulation. In my mind, that is addressing (some of) MECFS pathophysiology rather than just masking symptoms, but perhaps the devil is in the terminology.

 

I have the genetic markers for the IDO2 metabolic trap (checked by Robert Phair). Abilify did nothing for me, at any doses.

 

You may interpret Jonathan's post like that, I don't. He's stating what the rituximab trial showed us.