Abilify (aripiprazole)

[apsig]

A number of months ago, my psychiatrist recommended I try aripiprazole for the treatment of depression. I am somewhat opposed to the use of antipsychotics in the treatment of such conditions, but I went along with it and received a 14-day sample pack.

I ended up taking it for two days and simply felt stupid whilst on it. After conveying this information to my doctor, he said it was likely placebo effect, as it "takes two to three weeks to work". Nonetheless, he accepted my disinterest in taking the medication and other approaches were tried.

Does his assertion make sense to anyone here?

The effects of aripiprazole according to wikipedia are:


D2 Partial Agonist (Ki = 0.34 nM)
D3 Antagonist (Ki = 0.8 nM)
D4 Antagonist (Ki = 44 nM)
5-HT1A Partial Agonist (Ki = 0.34 nM)
5-HT2A Antagonist (Ki = 0.8 nM)
5-HT2C Partial Agonist (Ki = 15 nM)
5-HT7 Antagonist (Ki = 39 nM)
SRI (Ki = 98 nM)
Antihistamine (Ki = 61 nM)
α-adrenergic antagonist (Ki = 57 nM)
mACh receptor antagonist (IC50 >1000 nM)


Wouldn't most of these mechanisms be active immediately upon penetration of the BBB?

Granted, any downregulatory/upregulatory responses may take a few weeks, but I would assume that receptor antagonism could be noticeable on the first day. Am I way off on this, or was his explanation questionable?

 

[Deleted member 170540]

Something you said to your psychiatrist probably made him/her think that you're psychotic... Aripiprazole is never prescribed for depression, its only used for psychotic disorders. If you feel bad and paranoid then aripiprazole might help you but theres also the possibility that the doctor is mistakingly treating you as a psychotic patient.

 

[negrogesic]

Personally, I dislike it.........but more over the concern of its over-prescription

Your doctor is telling you the typical bullshit. The drug has an immediate effect, while true, according to the Rx material, the maximum purported "benefit" is a function of time.

The better question; why are you on it to begin with? What is your "diagnosis"? I don't practice psychiatry, but I've never written a script for the drug, and the only "anti-psychotic" drug I feel comfortable using in people devoid of PSYCHOSIS, is seroquel. Abilify will certainly make you act and feel "dumb", and was improperly indicated by the FDA and obscenely and unethically marketed direct to the consumer via television campaign.

Ask your psychiatrist about its mechanism of action (don't expect him to give you Ki values, but he 'technically' should know what it does), and moreover, why he chose it over alternatives. If he reaches for the PDR, walk out of the room and do not pay his bill (haha, I know this is not an option for everyone, although it ideally should be).....

 

[negrogesic]

Oh, and as to those abilify "sample" packs, I literally see these things dispersed everywhere, the reps are pushing this shit with some serious force, and im sure many physicians don't give a shit and just want to get rid of it......

 

[Smyth]

My problem when I took this compound was this: I took the tablet during the morning without really much effect. By evening time it had metabolized to something speedy that kept me awake at night. All this happened with 15mg per day.

Im thinking the active metabolite is likely to be 2,3-dichlorophenylpiperazine. Still, this seems like rather a low dosage (15mg) whereas the dose of benzylpiperazine which is required to have a speedy effect is maybe 200mg at least. I cant figure this one out. Maybe it is metabolized to something different? But it seems like the Abilify wasnt doing anything in itself and needed to take several hours before it started having an effect on me. So im guessing that it could be a prodrug to a different compound.

 

[23536]

Something you said to your psychiatrist probably made him/her think that you're psychotic... Aripiprazole is never prescribed for depression, its only used for psychotic disorders.

maybe in Europe is it never prescribed for depression--and correctly so. In the US it is being very aggressively prescribed for depression with or without psychotic features.

In my area, quetiapine is widely prescribed for depression as well. Specifically for sleep disturbances associated with depression. Aripiprazole won't help you sleep like quetiapine will, so at least it has that going for it.

It is very common for a perfunctory psychiatrist to misdiagnose psychotic features. Shit, if they're robotically telling everyone the same "2 or 3 weeks to see an effect" cliche, they're not really paying close attention to the patient.

 

[apsig]

No, there were no symptoms of psychosis whatsoever. He recommended I try it after I had little to no response to a combination of 10 mg escitalopram and 400 mg bupropion daily in the treatment of depression.
As noted above, Abilify is being pushed heavily as an adjunct for SSRI/SNRI treatment in nonresponding patients. I hated it, as it only made the cognitive deficits of depression worse, which merely made me more depressed.

Then again, FWIW, this psychiatrist told me that downregulation is not a concept supported by medical literature, so....



I must at least give him credit for the fact that he 100% supported my decision not to take the drug, though.

 

[ebola?]

Then again, FWIW, this psychiatrist told me that downregulation is not a concept supported by medical literature, so....

Sounds rad. I'm going to take speed every day now. XD
...
What's up with these newer atypicals that seem to be getting less and less selective?

ebola

 

[apsig]

^^Haha

Granted, he was speaking in regards to the serotonin system, but still

Nice guy, but methinks he needs to read some stuff not published by the drug manufacturers....

 

[23536]

What's up with these newer atypicals that seem to be getting less and less selective?

the diseases are adapting

 

[atara]

I ended up taking it for two days and simply felt stupid whilst on it. After conveying this information to my doctor, he said it was likely placebo effect

My understanding is that any clinically significant dopamine antagonist is going to inhibit cognitive function, period. I like my dopamine receptors as they are -- functioning!

What's up with these newer atypicals that seem to be getting less and less selective?

Less selective was the point of the atypicals in the first place. 5-ht antagonism was found to prevent ugly side effects like ataxia and akathisia. Haloperidol is really selective, for example.

 

[Smyth]

Sounds rad. I'm going to take speed every day now. XD
...
What's up with these newer atypicals that seem to be getting less and less selective?

ebola

I take it you didnt read the SNDRI article I wrote on wikipedia then?

The issue of drug promiscuity is covered by article citations 16-23 (and articles cited therein), but if you are particularly pressed for time then concentrate on reading Bryan Roths' article. If you dont have institutional access then you can get this one:

http://www.ncbi.nlm.nih.gov/pubmed/20704963

 

[ebola?]

Looks like useful reading. Thanks. While I was aware that serorotonergic antagonism (specific to where, again?) reduces extrapyramidal side-effects, I was beginning to wonder why more and more recent psychiatric meds seem to have bizarrely broad spectra of activity.

ebola

 

[apsig]

I know it would be no easy task, and that many illnesses are the result of dysfunction of multiple systems, but I think it would be amazing for (qualified and experienced) physicians to have a library of highly selective drugs that target individual receptor systems in agonist/antagonist/partial agonist forms.

So then, one could go to a compounding pharmacy and get a pill made with a cocktail of molecules to target different receptors as specified by your psych/neurologist.

Of course, perhaps it will turn out that blocking and activating receptor sites is ultimately not the best way to treat these illnesses, but such a project would certainly help us out in acquiring more knowledge of brain function...

 

[Smyth]

I thought the reason why drugs like riperidone have less extrapyramidal symptoms when compared to the typicals like haloperidol is that more emphasis is placed on 5HT2A receptor antagonism whereas the latter solely functions as a D2 receptor antagonist with little activity at other receptors. I believe it is the relative lack of antagonist (c.f. aripiprazole) affinity for D2 receptors that makes the atypical less likely to exhibit extrapyramidal symptoms. I dont think the 5HT receptors have got anything to do with that per se.

Chlorpromazine will only produce EP symptoms when high dosages are employed whereas haloperidol has an intrinsic tendancy to produce EP symptoms even at low doses. The latter drug is still in the core list of essential medicines according to the WHO so it may still have uses.

 

[StaySedated]

Something you said to your psychiatrist probably made him/her think that you're psychotic... Aripiprazole is never prescribed for depression, its only used for psychotic disorders. If you feel bad and paranoid then aripiprazole might help you but theres also the possibility that the doctor is mistakingly treating you as a psychotic patient.

Aripiprazole is used along with an SSRI to treat depression.

 

[MeDieViL]

Meh, abilify is more likely to induce parkinson like shit compared to the other atypicals, useless junk.

 

[thomasc93]

Meh, abilify is more likely to induce parkinson like shit compared to the other atypicals, useless junk.

agreed. it has no place IMHO in the treatment of depression. hell, I wouldn't even take it if I had schizophrenia; I would just stick with clozapine or risperidone or something.

 

[PsychedelicPeptide]

I thought most of the broad activity you see from these pharm small molecules is because they usually pull the starting molecular backbone down from library screens and thus it is hard to get rid of all the undesired activities without destroying the desired activity all together.

Then once they get a hit they will make analogs to try and optimize the molecule, but obviously you can only get so far working with this strategy in terms of ideal receptor profiles. Ideally they would use receptor models as a starting point but most people just aren't smart enough to put all the puzzle pieces together, or they unfortunately want the "easy way" out: throw X thousand random molecules at the target, find a hit, have your "I can only synthesize not rationalize" chemist workforce synthesize analogs based on what analogs are easy to make or have simple modifications, screen again --> bam there's your first candidate.

With a little luck you won't have toxicity and will see effect in rodents. This is all they want. Have a few human trials with some cases of successful treatment... then apply for FDA approval, no questions asked about the side activities.

Besides it probably won't be until other people start testing their molecule that they figure out about them anyways!

 

[Alcyone]

^ Good point, I guess. Small molecular drugs aren't very clean, in the sense that they more often than not display unwanted side activities. But I think it's a bit more complicated than that.

If I may go off on a little rant myself, I believe that many drugs currently used in psychiatry are "dirty" by intent and not by misfortune. In recent years, neurobiologists and psychopharmacologists have realised that they don't understand the mechanisms of depression after all. There's also the almost universal misconception that depression, anxiety, and to some extent psychotic disorders, are closely interlinked. Textbooks will have to be re-written, and in the meantime the medical community is gleefully dispensing pharmacological pipe bombs such as mirtazapine, aripiprazole and quetiapine, assuming that at least one or two of the multiple receptors that they hit would be relevant in treating pretty much any psychiatric condition.

Somewhat exaggerated, of course.