Abilify was originally intended as an anti-psychotic .... it's a partial dopamine agonist as opposed to a dopamine antagonist or blocker like most of the earlier, first-generation antipsychotics.for most of us (2/3?) Abilify builds up (pharmarkokinetic?) tolerance.
Any theories why?
Hiya @Push Fwd and @Martin aka paused||M.E. ....If it would be a problem with receptors then a break should help to let the brain rebuild it.
for most of us (2/3?) Abilify builds up (pharmarkokinetic?) tolerance.
Any theories why?
Maybe workarounds possible?
Well in the down-regulation of GABA receptors caused by benzodiazepine use, it appears to be histone deacetylation (an epigenetic mechanism) which is responsible. See this study.
If the loss of effect of Abilify also involves histone deacetylation, then possibly histone deacetylase (HDAC) inhibitors might act to restore the effect of Abilify. HDAC inhibitors have been shown to reduce morphine tolerance.
Valproic acid is one HDAC inhibitor, and there are several other HDAC inhibitor drugs available. Butyrate is another HDAC inhibitor. The probiotic Clostridium butyricum is a butyrate-producing bacterium.
Source : https://www.healthrising.org/blog/2...gregor-metabolism-chronic-fatigue-glycolysis/The Tie That Binds…
McGregor then shifted gears and proposed – using a gene expression exercise study by Whistler et. al. – that the tie that binds all this together may be massive levels of something called histone deacetylation (performed by histone deacetylase enzymes or HDACs). He noted that histone acetylation/deacetylation regulated the top twenty genes found altered in Whistler’s study. A similar outcome was found in a genetic polymorphism study.
Neil McGregor believes HDAC is involved.
Source : https://www.healthrising.org/blog/2...gregor-metabolism-chronic-fatigue-glycolysis/
people with ME/CFS are having trouble “acetylating”; i.e. using acetyl groups to regulate our gene expression.
If that's accurate, it's the same enzyme that metabolizes benzos, so anything that inhibits the metabolizing of benzos should do the same, at least to some degree, for Abilify ...If I'm not wrong I remeber that Abilify is metabolized by CYP3A4.
If you're speaking from personal experience I'd have to agree. But that's not the experience of anyone that's reported on their experience with benzo withdrawal. Once most systems have been sensitized by tolerance or cold turkey withdrawal, their response to benzos is altered for a very long time, and the incidence of tolerance withdrawal greatly increased and accelerated with future use.As it goes for benzos: 2 Weeks off and they work exactly as they did before withdrawal.
Once most systems have been sensitized by tolerance or cold turkey withdrawal, their response to benzos is altered for a very long time, and the incidence of tolerance withdrawal greatly increased and accelerated with future use.
It would be interesting to see if the Abilify loss of effect reverses itself after discontinuing the drug for some weeks, or whether the loss of effect is permanent
A depressingly plausible possibility ....If you are taking a treatment like Abilify where too much activity still causes crashes but you don’t get any overexertion signals like PEM then it makes sense it was masking the negative effects overexertion has on the disease process, otherwise you wouldn’t crash.
This makes sense, logically, even as I hope that it's totally wrong.It doesn’t take a big mental leap from this to postulate that even if you aren’t crashing on Abilify you could still be chronically overexerting and not realize it, all the while it having a big negative effect on the disease process until suddenly the drug doesn’t work anymore.