Abilify- Stanford Clinic Patients

[hmnr asg]

@hmnr asg

Any update on your restart?

Not doing well! The first time around it was almost miraculous. Now its like 10% improvements. I went to 2mg since 1mg wasnt doing much, hopefully 2 is better than 1. It's still better than nothing.

Do people here who’ve taken or are taking Abilify experience the same thing? Did you sleep less but had better quality sleep and/or woke up feeling less shitty?

Absolutely! I slept three hours less but woke up feeling refreshed. Now I sleep more and wake up feeling like death.

 

[Ski_again]

Is there any correlation between people's response to Abilifi vs LDN?

I tried LDN 1.5mg and it sent me into a crash for days. A few months later, tried half a cap (0.7mg) and it produced a mini crash. Very afraid of it now. This time I've been prescribed Abilifi 0.25 mg (due to symptoms of trembling and neuropathy), but after scanning through this thread I realize it is not to be trifled with, so I'm just looking for clues in advance before it arrives in the mail.

 

[leokitten]

Is there any correlation between people's response to Abilifi vs LDN?

I tried LDN 1.5mg and it sent me into a crash for days. A few months later, tried half a cap (0.7mg) and it produced a mini crash. Very afraid of it now. This time I've been prescribed Abilifi 0.25 mg (due to symptoms of trembling and neuropathy), but after scanning through this thread I realize it is not to be trifled with, so I'm just looking for clues in advance before it arrives in the mail.

There is no correlation or anything that can predict ahead of time if you will respond to any treatment for ME/CFS. It’s always a crapshoot.

 

[jaybee00]

@hmnr asg

Sorry to hear—are you back to 6 hours out of bed or is it still only 2 hours out of bed?

Since coming off Abilify I spend most of my day in bed. I don’t know if this is from the Abilify or from natural progression of the disease.

 

[jaybee00]

There is a post on FB from someone who got positive relief from CFS from rexulti https://en.m.wikipedia.org/wiki/Brexpiprazole
Same class as Abilify. I think this drug is also subject to poop-out. Some people on this review site report loss of effect after a certain amount of time.

https://www.drugs.com/comments/brexpiprazole/rexulti.html

 

[Martin aka paused||M.E.]

There is a post on FB from someone who got positive relief from CFS from rexulti https://en.m.wikipedia.org/wiki/Brexpiprazole
Same class as Abilify. I think this drug is also subject to poop-out. Some people on this review site report loss of effect after a certain amount of time.

https://www.drugs.com/comments/brexpiprazole/rexulti.html

Yes and you'll probably have a cross tolerance do no benefit

 

[jaybee00]

Maybe/maybe not

 

[bensmith]

I would recommend if people are interested to read this new ME hypothesis paper and thread discussion

https://forums.phoenixrising.me/thr...elitis-chronic-fatigue-syndrome-me-cfs.82761/

After doing some background reading, I realized there could be a possible mechanism here for how Abilify might improve symptoms in ME.

The hypothalamus is innervated by, and therefore responsive to and regulated by, dopamine, serotonin, and noradrenergic systems in the brain. It is also responsive to and regulated by many hormones and other signals in the endocrine and other systems.

So if this hypothesis is true and there is a central dysfunction in hypothalamic and pituitary gland function that ricochets throughout the entire endocrine system causing deleterious systemic effects and a vicious reinforcing cycle, then maybe Abilify’s actions at the monoamine systems improve hypothalamus function.

I thought a possible mechanism for why Abilify stops working after a while would be related to this vicious reinforcing cycle described in the paper. Maybe the hypothalamus, even with partial improvement in function, is still getting all these other signals reinforcing dysfunction, and these eventually are stronger than the positive effects Abilify has on the hypothalamus via monoamine systems, so the hypothalamus eventually falls back to its dysfunctional state.

This resonates with my condition. Do we have any tools for hypo repair? I have looked at team doing some kind of drug for narcolepsy, i know hypo is inolved in that.

I wonder then would people be able to take ssri/abilify etc and be “cured”. I’m sure this combination has been tried.

 

[leokitten]

This resonates with my condition. Do we have any tools for hypo repair? I have looked at team doing some kind of drug for narcolepsy, i know hypo is inolved in that.

I wonder then would people be able to take ssri/abilify etc and be “cured”. I’m sure this combination has been tried.

Researchers in the chronic critical illness community have been wanting to do clinical trials of hypothalamus releasing hormones to reset the anterior pituitary and eventually break the dysfunctional endocrine and inflammation cycle. Haven’t been done yet. Simply taking various exogenous hormones doesn’t work and feedback loops in endocrine system can make things worse.

 

[S-VV]

If abylifys mechanism is related to dopamine increase, I think L-DOPA would work as well for a few years, maybe with carbidopa and seleguiline once it starts lo loose it's effects.

 

[leokitten]

If abylifys mechanism is related to dopamine increase, I think L-DOPA would work as well for a few years, maybe with carbidopa and seleguiline once it starts lo loose it's effects.

I don’t think that’s been posited as a hypothesis, otherwise e.g. regular dopamine agonists would show significant benefits across a lot of pwME yet there are very few reports of that.

Currently to me these are the hypotheses for Abilify efficacy in ME:

1. Dopamine-serotonin system stabilizer
2. Anti-neuroinflammatory
3. Positively effects ME cellular metabolism dysfunction
4. Positively effects possible ME hypothalamus and pituitary gland dysfunction

As you can tell these hypotheses are overlapping and it could be all of these.

I’ve been reading papers to look more closely at 3 and 4 but it’s been slow going as takes a lot of background reading. Aripiprazole affects cellular metabolism and energy sensing as well as endocrine function. Antipsychotics all do but they have really different effects depending on the drug.

 

[andyguitar]

4. Positively effects possible ME hypothalamus and pituitary gland dysfunction

I'd put my money on this.

 

[leokitten]

Today is day 5 of my trial of Abilify 0.25 mg.

I don’t feel any different than before, still have so much fatigue and dizziness that I can’t get out of bed for more than 1 hour or so a day. I’ve had severe insomnia and sleep disturbances before treatment so don’t notice any significant worsening. I also am not experiencing any negative effects like others have mentioned experiencing during their first week on treatment, I don’t really notice any difference to my regular ME shitty feeling.

 

[leokitten]

What happens? Does it just suddenly get better from one day to the next in a few days?

 

[hmnr asg]

What happens? Does it just suddenly get better from one day to the next in a few days?

If you are not even experiencing side effects maybe go up to 1mg?

 

[leokitten]

If you are not even experiencing side effects maybe go up to 1mg?

I am going to wait until the 2 week mark as Abilify plasma concentration continues to increase to steady state then. If I don’t notice anything then will go up to 0.5 mg for another two weeks, and so on.

The reason I’m doing this is because it’s the only way to see what’s the minimum effective dose for a person.

 

[leokitten]

Antipsychotics differentially regulate insulin, energy sensing, and inflammation pathways in hypothalamic rat neurons. Kowalchuk et al. Psychoneuroendocrinology (2019)

Introduction: Second generation antipsychotic (AP)s remain the gold-standard treatment for schizophrenia and are widely used on- and off-label for other psychiatric illnesses. However, these agents cause serious metabolic side-effects. The hypothalamus is the primary brain region responsible for whole body energy regulation, and disruptions in energy sensing (e.g. insulin signaling) and inflammation in this brain region have been implicated in the development of insulin resistance and obesity. To elucidate mechanisms by which APs may be causing metabolic dysregulation, we explored whether these agents can directly impact energy sensing and inflammation in hypothalamic neurons.

Methods: The rat hypothalamic neuronal cell line, rHypoE-19, was treated with olanzapine (0.25-100 uM), clozapine (2.5-100 uM) or aripiprazole (5-20 uM). Western blots measured the energy sensing protein AMPK, components of the insulin signaling pathway (AKT, GSK3β), and components of the MAPK pathway (ERK1/2, JNK, p38). Quantitative real-time PCR was performed to determine changes in the mRNA expression of interleukin (IL)-6, IL-10 and brain derived neurotrophic factor (BDNF).

Results: Olanzapine (100 uM) and clozapine (100, 20 uM) significantly increased pERK1/2 and pJNK protein expression, while aripiprazole (20 uM) only increased pJNK. Clozapine (100 uM) and aripiprazole (5 and 20 uM) significantly increased AMPK phosphorylation (an orexigenic energy sensor), and inhibited insulin-induced phosphorylation of AKT. Olanzapine (100 uM) treatment caused a significant increase in IL-6 while aripiprazole (20 uM) significantly decreased IL-10. Olanzapine (100 uM) and aripiprazole (20 uM) increased BDNF expression.

Conclusions: We demonstrate that antipsychotics can directly regulate insulin, energy sensing, and inflammatory pathways in hypothalamic neurons. Increased MAPK activation by all antipsychotics, alongside olanzapine-associated increases in IL-6, and aripiprazole-associated decreases in IL-10, suggests induction of pro-inflammatory pathways. Clozapine and aripiprazole inhibition of insulin-stimulated pAKT and increases in AMPK phosphorylation (an orexigenic energy sensor) suggests impaired insulin action and energy sensing. Conversely, olanzapine and aripiprazole increased BDNF, which would be expected to be metabolically beneficial. Overall, our findings suggest differential effects of antipsychotics on hypothalamic neuroinflammation and energy sensing.

 

[leokitten]

There aren’t a lot of papers on this subject but as you can see from this paper it’s kind of inconclusive and equivocal. Aripiprazole seems to have some good hypothalamic actions and some bad. Though since so little research has been done on this topic I would say likely most is still unknown.

 

[leokitten]

The time of day when you take Abilify seems to alter its side effect on metabolic parameters. I know many of you were already doing it, but long story short, take Abilify in the morning!

Does the Time of Drug Administration Alter the Metabolic Risk of Aripiprazole? Chipchura et al. Front Psychiatry (2018)

Antipsychotic drugs cause metabolic abnormalities through a mechanism that involves antagonism of D2 dopamine receptors (D2R). Under healthy conditions, insulin release follows a circadian rhythm and is low at night, and in pancreatic beta-cells, D2Rs negatively regulate insulin release. Since they are sedating, many antipsychotics are dosed at night. However, the resulting reduction in overnight D2R activity may disrupt 24 h rhythms in insulin release, potentially exacerbating metabolic dysfunction. We examined retrospective clinical data from patients treated over approximately 1 year with the antipsychotic drug aripiprazole (ARPZ), a D2R partial agonist. To identify effects of timing on metabolic risk, we found cases treated with ARPZ either in the morning (n = 90) or at bedtime (n = 53), and compared hemoglobin A1c, and six secondary metabolic parameters across the two groups. After controlling for demographic and clinical factors, patients treated with ARPZ at night had a significant decrease in HDL cholesterol, while in patients who took ARPZ in the morning had no change. There was a non-significant trend toward higher serum triglycerides in the patients treated with ARPZ at night vs. morning. There were no group differences in hemoglobin A1c, BMI, total cholesterol, LDL cholesterol, or blood pressure. Patients taking APPZ at night developed a worse lipid profile, with lower HDL cholesterol and a trend toward higher triglycerides. These changes may pose additional metabolic risk factors compared to those who take ARPZ in the morning. Interventions based on drug timing may reduce some of the adverse metabolic consequences of antipsychotic drugs.

 

[leokitten]

Hopefully soon another new dopamine-serotonin stabilizer Brilaroxazine (also known as Oxaripiprazole) will be out in the market.

https://en.m.wikipedia.org/wiki/Brilaroxazine

It’s almost identical molecular structure to aripiprazole, with only a single carbon change in the quinolinone ring system to oxygen making it a benzoxazinone ring system. The resulting change also makes it closely related to cariprazine.

Brilaroxazine (RP5063) Clinical Experience in Schizophrenia: "A New Option to Address Unmet Needs"

Dopamine serotonin stabilizer RP5063: A randomized, double-blind, placebo-controlled multicenter trial of safety and efficacy in exacerbation of schizophrenia or schizoaffective disorder. Cantillon et al. Schizophr Res (2017)

RP5063, an atypical antipsychotic drug with a unique pharmacologic profile, improves declarative memory and psychosis in mouse models of schizophrenia. Rajagopal et al. Behav Brain Res (2017)

Brilaroxazine (RP5063) seems to have fewer potential side effects compared to aripiprazole (which itself already had fewer side effects than other antipsychotics).

Brilaroxazine doesn’t seem to cause any metabolic side effects compared to placebo and other antipsychotics, which is a big improvement compared to even aripiprazole. Patient’s glucose, lipids, and prolactin all actually decreased, and there were no significant changes in weight.

@Janet Dafoe I think Ron was looking for an alternative dopamine-serotonin stabilizer drug with a similar mechanism of action and binding profile to aripiprazole but doesn’t have the negative metabolic side effects, well brilaroxazine seems to be a good candidate.

They’ve already completed phase 1 and phase 2 trials for schizophrenia and are preparing phase 3 (https://revivapharma.com/clinical-trails/). Reviva Pharmaceuticals who is developing brilaroxazine is in Santa Clara, CA so just around the corner from you! https://revivapharma.com/