Abilify- Stanford Clinic Patients

leokitten

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I just was thinking... isn't it likely that the Stanford Clinic would probably discontinue using Abilify as a firstline treatment if the drug stopped working after weeks to a few months in most patients? Just trying to get a rough idea of the incidence of waning efficacy. Does anyone know what's the longest time people there have been taking it?
 

jaybee00

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I just was thinking... isn't it likely that the Stanford Clinic would probably discontinue using Abilify as a firstline treatment if the drug stopped working after weeks to a few months in most patients? J
Not necessarily. The effectiveness of antivirals wane over time until they don’t work, yet many clinicians still prescribe them.
 

leokitten

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Not necessarily. The effectiveness of antivirals wane over time until they don’t work, yet many clinicians still prescribe them.
Ok, though I thought antivirals worked for the people that saw improvements on them for longer than a few months?
 

leokitten

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I just was thinking... isn't it likely that the Stanford Clinic would probably discontinue using Abilify as a firstline treatment if the drug stopped working after weeks to a few months in most patients? Just trying to get a rough idea of the incidence of waning efficacy. Does anyone know what's the longest time people there have been taking it?
Dear @Janet Dafoe - I know you are probably very busy, I was just wondering if you do have some time if you know or can ask Ron a follow-up question regarding his video where he said at the Stanford ME Clinic that ~80% patients were responders to Abilify.

There have been reports from some patients that Abilify gave significant improvements and then started waning in efficacy and stop working after weeks to a few months, even after increasing the dosage. Since there is a small risk of very serious side effects with Abilify then the risk might not be worth it for some patients if it turns out to only work a few months in most pwME.

Would you or Ron know (or be able to find out) the percentage of total patients who've been given Abilify at Stanford who are maintaining long-term efficacy and for how long it's been continuously working on average in these patients?

Thank you and all the best
 
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nyanko_the_sane

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Pharmacodynamics of Aripiprazole
Aripiprazole exhibits high affinity for dopamine D2 and D3, serotonin 5-HT1A and 5-HT2A receptors (Ki values of 0.34 nM, 0.8 nM, 1.7 nM, and 3.4 nM, respectively), moderate affinity for dopamine D4, serotonin 5-HT2C and 5-HT7, alpha1-adrenergic and histamine H1 receptors (Ki values of 44 nM, 15 nM, 39 nM, 57 nM, and 61 nM, respectively), and moderate affinity for the serotonin reuptake site (Ki=98 nM).
Abilify is one of those enigmas of the pharmacological world, it works, but the mechanism of action is not understood. Brain inflammation is associated in some of the mental disorders abilify is used to treat. So it stands to reason that a drug that may work on immune response in the brain, might make a difference in PWME. Since abilify is working for some, this gives validation to the autoimmune nature of ME/CFS. Does this make sense to you?

Detailed information on Abilify

Increased autoimmune activity against 5-HT: a key component of depression that is associated with inflammation and activation of cell-mediated immunity, and with severity and staging of depression

The Effects of Serotonin in Immune Cells
 
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leokitten

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You are unlikely to get a reliable answer to that question because physicians will tend to exaggerate benefits or more likely won’t do any long-term follow up.
Could you explain what you think the possible benefits would be for Stanford to do this? They have waiting lists of patients so they don't need to drum up new patients for money etc. I only see negative consequences of reporting much higher than the real anecdotal long-term efficacy rates at different time lengths they are seeing. Plus I'm pretty certain ME doctors easily keep track of patient drug response, my ME doctor always is folllowing up the next time I see her on if a drug treatment worked and how long etc. My answers are easy because nothing ever worked LOL. Do you not see or talk to your ME doctor for very long periods of time (years)?
 

leokitten

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Here are a couple additional possible mechanisms of action for Abilify which I searched against the ME neurological functional and structural evidence cataloged in this recent and good systematic review paper.

A systematic review of neurological impairments in myalgic encephalomyelitis/chronic fatigue syndrome using neuroimaging techniques (2020)


Cingulate cortex multiple dysfunctions in ME (cerebral blood flow, neuroinflammation, serotonin transporter deficiency, glucose hypomethylation, cognitive dysfunction, etc) : aripiprazole seems to increase regional cerebral blood flow and improve cognition to anterior cingulate cortex

The relationship between dopamine receptor blockade and cognitive performance in schizophrenia: a [11C]-raclopride PET study with aripiprazole
After switching from first-generation antipsychotics (FGA) such as haloperidol to aripiprazole, the blood-oxygen-level-dependent signal measured in the anterior cingulate cortex in patients with schizophrenia increased during cognitive function tasks21. They also showed performance improvement in memory, attention, and executive function tests after switching to aripiprazole22,23. Moreover, verbal cognitive function in patients improved after switching from second-generation antipsychotics and other FGAs to aripiprazole3,24.
Acute effects of single-dose aripiprazole and haloperidol on resting cerebral blood flow (rCBF) in the human brain
Further increases [in regional cerebral blood flow] were evident in the insula, hippocampus, and anterior cingulate after both antipsychotics

Hippocampus dysfunction and neuroinflammation in ME: aripiprazole appears to promote hippocampal growth and improve memory performance (though evidence is not robust)

The effect of second-generation antipsychotics on hippocampal volume in first episode of psychosis: longitudinal study
Aripiprazole subgroup displayed significant increases in bilateral hippocampal volume compared with all other subgroups
Bulking up the hippocampus in schizophrenia: a role for 5-HT1A agonists?
Although speculative, the agonist activity of aripiprazole at the 5-HT1A receptor may be relevant to its differential effect on hippocampal volume compared with other antipsychotic agents examined by Bodnar and colleagues. The 5-HT1A receptors are major inhibitory G-protein-coupled receptor subtypes found on pre- and post-synaptic neurons throughout the brain. They are highly expressed in brain regions implicated in affect regulation and memory processing, including the hippocampus, particularly in the CA1 region, the amygdala and in the frontal, cingulate and entorhinal cortices.11 5-HT1A receptors influence dopaminergic, cholinergic, glutamatergic and GABAergic functions. In this context, 5-HT1A receptor agonists have been considered as potentially pro-cognitive on the basis of preclinical evidence that they modulate the release of cortical and hippocampal dopamine and acetylcholine.11
Improving cognition in schizophrenia with antipsychotics that elicit neurogenesis through 5-HT(1A) receptor activation
Mechanisms by which hippocampal adult neurogenesis can be increased are therefore of therapeutic interest and a promising molecular target is the activation of serotonin 5-HT(1A) receptors because agonists at this site increase adult neuronal proliferation in the dentate gyrus. We hypothesize that use of antipsychotics possessing 5-HT(1A) receptor agonist properties may protect against or attenuate CIAS by a dual mechanism: a favorable influence on adult neurogenesis that develops upon sustained drug treatment, and an increase in dopamine levels in the prefrontal cortex that starts upon acute treatment.
 
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leokitten

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I forgot to also summarize the potential mechanism of action already discussed in this thread and mentioned in the review paper:

Miller et al. [41] who described neuroinflammation as a potential mechanism underlying impaired neurotransmission in the basal ganglia. These features strongly suggest a neuroimmune process underlying ME/CFS pathology.
The cingulate cortex has strong reciprocal connections to the orbitofrontal cortex, the basal ganglia and the insula. The basal ganglia have important roles in reward-processing. Dysfunction of the basal ganglia has also been implicated in ME/CFS [41]. A fMRI study by Miller et al. [41] found that when performing a monetary gambling task, the right caudate and right globus pallidus were found to have significantly less activation in ME/CFS patient groups compared with HCs. The decreased activation detected in the right globus pallidus correlated with increased mental fatigue, general fatigue and reduced activity [41].

Basal ganglia reduced activity and neuroinflammation in ME: one of aripiprazole's main mechanisms of action (in a very simplified and reductionist way) is that it stabilizes dysfunctional dopamine neuron firing and neurotransmission in a functionally selective way in the both the striatum and extrastriatal dopamine regions. Of course in reality it's more complex but not needed for this point. It's other main mechanisms of action at serotonin receptors also play there own part and interact with dopamine neurons.

Decreased Basal Ganglia Activation in Subjects with Chronic Fatigue Syndrome: Association with Symptoms of Fatigue
Compared to non-fatigued controls, patients with CFS exhibited significantly decreased activation in the right caudate (p = 0.01) and right globus pallidus (p = 0.02). Decreased activation in the right globus pallidus was significantly correlated with increased mental fatigue (r2 = 0.49, p = 0.001), general fatigue (r2 = 0.34, p = 0.01) and reduced activity (r2 = 0.29, p = 0.02) as measured by the Multidimensional Fatigue Inventory. No such relationships were found in control subjects. These data suggest that symptoms of fatigue in CFS subjects were associated with reduced responsivity of the basal ganglia, possibly involving the disruption of projections from the globus pallidus to thalamic and cortical networks.
One mechanism that may contribute to alterations in function and neurotransmission in the basal ganglia in CFS is inflammation [47]. CFS patients have been shown to exhibit a number of immune alterations including the presence of increased inflammatory markers in the peripheral blood and increased production of inflammatory cytokines in ex vivo preparations of peripheral blood mononuclear cells [12][15]. As noted above, a number of inflammatory stimuli including the inflammatory cytokine, interferon alpha and cytokine inducers such as endotoxin and typhoid vaccination have been shown to alter basal ganglia function while also leading to symptoms of fatigue including psychomotor slowing and reduced motivation, both fundamental behavioral processes regulated by basal ganglia structures [19], [20], [47], [48].
TSPO-PET/MRI Reveals Increased Neuroinflammation in Basal Ganglia of Chronic Fatigue Syndrome Patients (prepublished)
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease affecting millions of people in the United States alone, but little is known about the underlying pathophysiology. We show that simultaneous TSPO-PET/MRI measurements using [11C]DPA-713, including SUV, SUVr, QSM, R2*, and volume can uncover new information about this disease. We find that the putamen has significantly higher TSPO-PET signal in ME/CFS subjects compared to healthy controls, indicating an elevated inflammatory response in this area. This finding corresponds to previous fMRI and diffusion imaging findings and may help with future diagnosis and tracking of this chronic, widespread disease.
Plus there are a number of published papers finding aripiprazole exhibits neuroprotective and anti-inflammatory effects in various areas of the brain (sorry too tired now to bring them into this post)
 

bensmith

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I have a psych doctor who would give me abilify, not for cfs/me though. He thinks im nuts because of my me. Not sure if thats a food idead or not.

What do they monitor, just symptom improvement? I have hppd too so not sure i could. But interested.
 
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leokitten

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Don’t understand. Remember we cannot give direct medical advice to you on these threads.
If you mean just taking Abilify by itself without a COX-2 inhibitor or LDN? Anecdotal reports say combining with these is synergistic with Abilify and supposedly helps to prevent tolerance or ME-related waning efficacy. But each of us is a crap shoot so you never know Abilify might work for you without anything else or it might not, this is the hell of ME having to make these decisions about empirical treatments.
 

leokitten

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Does abilify come in 1 mlg doses? Going to get some from a psych doc maybe.
I would be very interested in hearing how it goes with your psych doc and Abilify. If your psych doc is well-trained and informed they will know that Abilify does not work at all as an antipsychotic at low dosages. If they are just open to letting you try it at the dosage you want that’s awesome, but hopefully they aren’t intending to Dx you as bipolar or schizophrenia and put the dosage all the way up to 15-30 mg / day.
 

bensmith

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he has incorrectly diagnosed me as schizo i think, but i have an extensive bistory of medicine sensitivity. Sub clinical working for me
Would not be odd. Im thinking .25 or lower if i can.

id like to add ldn and celebrex after, i think. Getting on abilify will likely be difficult.

meds are often difficult for me. Scared but hopeful, i am ready for some breathing room.