Whats the case with Abilify (aripiprazole)

[eastman18]

Hello guys, recently I have read a lot about the latest generation antipsychotics like aripiprazole and cariprazine. They have really unique mechanism of action. But I also read a lot of comments in this forum about withdrawal symptoms from abilify (dispite its long half life which is pharmacologically impossible), anhedonia (which is also impossible since it is 5HT1A partial-agonist, D2 partial agonist) and other ridiculous comments. I myself used to drink abilify 5 mg per day for anxiety, worked very well. But can someone provide more information about his own experience and possibly sum pharmacological evidence for mechanism of action that would explain those withdrawals.

 

[darvocet21]

I was prescribed 2mg day which had no noticeable effects, the doctor increased the dose to 5 mg which I took for a week or two and made me feel sluggish so I stopped.

 

[Jabberwocky]

Having suffered negative psychological effects subsequent to ceasing Abilify on 3 occasions I think there is cause to consider the-possibility that there are withdrawal effects despite the long half life. There is certainly a nascent literature on Antipsychotic Withdrawal Syndrome, however the subset of that which deal with Abilify specifically is negligible. In my case I was often taking other substances so I was never certain Abilify was really the issue, or perhaps whether ceasing Abilify while adding something else (say meth or acid) simultaneously created a new negative effect that was not purely withdrawal.

After searching the literature it seems most papers are clear that while SOME effects and mechanisms and actions of individual antipsychotics are known ALL are certainly not - therefore it’s a bit facile to go declaring anything definitively ‘impossible’ or ‘ridiculous’ in this field. Furthermore, because it is not required for approval processes, there are few incentives to study long term effects of these medications. SO just because Abilify is known to be a 5HT1A partial-agonist and a D2 partial agonist does not mean it is not acting in different ways on other receptors. It is mentioned in a number of papers that neuroplastic adaptive effects of anti-psychotics create the possibility for withdrawal effects, for example by promoting the growth of new receptors and/or creating the conditions for receptor hypersensitivity when the blockade is withdrawn.

If neuroplastic adaptations have occurred under the influence of the medication then the half-life of the medication may not be directly relevant to withdrawal. This paper discusses this: https://academic.oup.com/schizophre...doi/10.1093/schbul/sbab017/6178746?login=true

 

[eastman18]

Having suffered negative psychological effects subsequent to ceasing Abilify on 3 occasions I think there is cause to consider the-possibility that there are withdrawal effects despite the long half life. There is certainly a nascent literature on Antipsychotic Withdrawal Syndrome, however the subset of that which deal with Abilify specifically is negligible. In my case I was often taking other substances so I was never certain Abilify was really the issue, or perhaps whether ceasing Abilify while adding something else (say meth or acid) simultaneously created a new negative effect that was not purely withdrawal.

After searching the literature it seems most papers are clear that while SOME effects and mechanisms and actions of individual antipsychotics are known ALL are certainly not - therefore it’s a bit facile to go declaring anything definitively ‘impossible’ or ‘ridiculous’ in this field. Furthermore, because it is not required for approval processes, there are few incentives to study long term effects of these medications. SO just because Abilify is known to be a 5HT1A partial-agonist and a D2 partial agonist does not mean it is not acting in different ways on other receptors. It is mentioned in a number of papers that neuroplastic adaptive effects of anti-psychotics create the possibility for withdrawal effects, for example by promoting the growth of new receptors and/or creating the conditions for receptor hypersensitivity when the blockade is withdrawn.

If neuroplastic adaptations have occurred under the influence of the medication then the half-life of the medication may not be directly relevant to withdrawal. This paper discusses this: https://academic.oup.com/schizophre...doi/10.1093/schbul/sbab017/6178746?login=true

Hi and thanks for taking part of this thread. I do acknowledge that antipsychotics do cause withdrawals sometimes, it is the unique mechanism of abilify that troubles me how could it possibly cause the same withdrawals as other Second gen antipsychotics. Perhaps it is possible that serotonin system takes part in it. Just trying to understand the scientific explanation. What dose were you on and how sever were your withdrawals? I mean what i was used to read is about severe withdrawals not mild ones and those are the withdrawals that i cant figure out

 

[Rectify]

Cariprazine > Aripiprazole.

 

[eastman18]

Cariprazine > Aripiprazole.

both have same mechanism of action but different receptor affinity, so in some people is the opposite but yeah cariprazine is more than great and in most cases is even better than aripiprazole but that's my point, new antipsychotics like cariprazine and aripiprazole should be generally better than traditional second gen antipsychotics right? What is your feedback and why are such medications so hated?

 

[eastman18]

like you see abilify act primary on HT2b then D2 and D2 post synaptic receptors
after that it act on HT1a with selectivity less by 6.31 then dopamine 2 receptors which i used as returning point thats why it 1 and ht2b 0.48
this mean that with normal clinical dosage abilify will just act dopamine 2 and ht2b (no function really for this receptor)
so abilify is selective dopamine 2 partial agonist which have anti anhedonia effect and the withdrawal will be the opposite of what abilify do.
you can see that abilify is Histamine 3 legend but with unknown efficiency and with selectivity of 527 this mean you need the double by x527 times the normal dosage to make abilify interact with that receptor in clinically relevant manner.
selectivity is everything ♡

5ht2b - antagonists inhibit SERT => inverse agonists should do as well => increase serotonin. (it is known that 5ht2b activation causes increased serotonin reuptake => 5ht2b supression should stop increased serotonine reuptake). 5ht2b antagonists and inverse agonists are linked to serotonine syndrome arent they ? (not sure ofc)

My second question is:
"abilify is selective dopamine 2 partial agonist which have anti anhedonia effect and the withdrawal will be the opposite of what abilify do" - isn't that logically incorrect i mean, aripiprazole affects more d2 presynaptic receptor thus controlling the DA synthesis. In pubmet article it is stated that aripiprazole acts as dopamine regulator and as d2 postsynaptic antagonist only on high dosage. So discontinuing it will not necessarily cause opposite effect.

According to https://ajp.psychiatryonline.org/doi/pdf/10.1176/appi.ajp.2007.06091479 , at normal clinical dosages (10-30mg /day) for humans, it has occupancy in 5ht1a (mean 16%) and 5ht2b (mean 59%) and that seems more than clinically significant.

 

[AlphaMethylPhenyl]

Withdrawal can lie below the threshold of feeling it, but it does happen ("discontinuation syndrome" or the sort).

We can't go to psychopharm. to directly explain why a drug has its effects. Like why is bupropion indicated for depression and SAD syndrome if it doesn't work with serotonin?

Neuroscience itself is incomplete, too. For example, we have hardly studied one class (yes class) of brain cell called glia

Functionally, it works as mostly stimulating/dopaminergic at 5mg and under, oftentimes being useful as augmentation. At higher doses it's sedating (more of a major tranquilizer).

 

[darvocet21]

i have calculated the selectivity of abilify based on its affinity and efficiency (its a bit complicated i hope you can understand)

like you see abilify act primary on HT2b then D2 and D2 post synaptic receptors
after that it act on HT1a with selectivity less by 6.31 then dopamine 2 receptors which i used as returning point thats why it 1 and ht2b 0.48
this mean that with normal clinical dosage abilify will just act dopamine 2 and ht2b (no function really for this receptor)
so abilify is selective dopamine 2 partial agonist which have anti anhedonia effect and the withdrawal will be the opposite of what abilify do.
you can see that abilify is Histamine 3 legend but with unknown efficiency and with selectivity of 527 this mean you need the double by x527 times the normal dosage to make abilify interact with that receptor in clinically relevant manner.
selectivity is everything ♡

Interesting how 9 out of 10 searches for Abilify for injection return results for Abilify "Maintena" sustained release formula that works for a month after a single injection. Has anybody heard of any other antipsychotic let alone psychotropic drug that's administered once every 30 days? It strikes me as a particularly bad idea, even by Big Pharma's low standards.

What happens if a patient begins to develop symptoms of tardive dyskinesia? Or the rare but dangerous side effect 'neuroleptic malignant syndrome'? What happens if a patient shows symptoms of these or other adverse drug effects during the period between administrations? Are they seriously considering giving this to geriatric patients, whose risk of serious side effects is greater and possibly life-threatening?

I see that hasn't stopped Otsuka America Pharmaceutical Company's full-court advertising and promotional campaign (spoiler alert: psychiatrists can receive free samples...)

It sounds like Sublocade buprenorphine for once-monthly administration which is given in a similar dose range, perhaps utilizing the same or similar technology that allows for a smooth drug release curve and steady plasma levels. That might be justified in certain patients able to give their fully informed consent. Because for buprenorphine at least there's an antidote if too much is released at one time, or if the patient takes something that potentiates its effects including alcohol in excess. However I know of no antidote for aripiprazole

 

[AlphaMethylPhenyl]

I can think of risperidone, paliperidone, olanzapine, aripiprazole, haloperidol, and probably more in R@D for long-term injections. I think the range is two weeks to six months, depending on the shot. Considering its wide range on multiple GPCR types, it's at this point impossible to disentangle just what function leads to what effect, try as you may.

 

[thegreenhand]

i have calculated the selectivity of abilify based on its affinity and efficiency

i'm sorry, can you explain the motivation for your calculation?

perhaps i'm misunderstanding units here. but as i understand it, efficiency is a ratio of affinity to molecular size and thus:

(efficiency)(affinity) = [(affinity) / (size)] (affinity) = (affinity)^2 ??

what is the physical meaning of this?