Mental Health Aripiprazole (Abilify) & Selegiline / L-Deprynl (Emsam) Interaction Questions

[I_Hate_This_Place]

My apologies for cross / double posting but I haven't garnered the amount of response that I was hoping to in my original post in ADD.

As such I'm posting this again here as well as linking to the thread in ADD. The thread in ADD has garnered a reply with some information as well as a further response from myself. So if possible please refer to Aripiprazole (Abilify) & Selegeline / L-Deprenyl (Emsam) Interactions for further information / posting.

I would have posted the question here in the first place as it seemed like the appropriate forum but from past experience I figured ADD would garner the journal articles & the like I was looking for. Seeing as that has not occurred to the degree to which I would like I'm hoping that perhaps some of the members of this forum have any experience or information whatsoever regarding the concomitant use of Aripiprazole (Abilify) & Selegeline / L-Deprynl (Emsam).

The question I have is regarding as the thread title indicates; information regarding the concomitant use of aripiprazole (Abilify) & selegiline (Emsam). Without going into to many details yet my wife is currently on Abilify (aripiprazole), Klonopin (clonazepam) & Synthroid (levothyroxine). While looking at various ways to improve her mental health situation adding an MAOI to her medication regemine has come up.

I've searched various sites & been unable to find anything besides a single anecdotal post on a random forum on the usage of both concomitantly. I haven't been able to locate anything regarding the use of any MAOI in general (as opposed to selegiline specifically) & anti-psychotics concomitantly in the literature. From what I've found there appear to be no documented interactions. I was hoping someone in this forum might be able to provide me a little more insight into any possible interactions that could occur. I'm not positive that the lack of documentation regarding possible interactions indicates a lack of interactions or just a lack of documentation of said interactions.

The Dr. involved in her treatment does not make me particularly confident in his knowledge on this topic (or in general). I'm not as familiar as I'd like to be with selegiline & will continue to research any possible complications. A few possible interactions come to my mind...
However; rather than potentially jumping to erroneous conclusions I'd much prefer that someone more knowledgeable than I elucidate on the topic. Any input whatsoever is greatly appreciated. As I'm drawing a blank on locating more information on the subject regardless of my attempts to locate it.
Through search or other means.

Based on the responses I can provide further information if needed.

Hopefully someone here can help to shed some light on the subject. We extend our gratitude to anyone able to provide any insight on the matter.

Thanks to anyone that can provide any information or insight. Academic or source based answers are preferred but at this point I'd be happy to get any information whatsoever. Also any information regarding the use of MAOI's in general with aripiprazole would perhaps help. Actually any information regarding the use of MAOI's & any other substance that has a similar pharmacological profile as aripiprazole. If you read the thread in ADD we where able to find a little on the use of aripiprazole in conjunction with perphen-azine or haloperidol in Selegiline in the treatment of sexual dysfunction in schizophrenic patients maintained on neuroleptics: a pilot study but that is pretty much the extent of what we've located regarding the use of any MAOI. I've not been able to locate any literature on the combination of the 2 outside of the 1 case report that was linked in the reply in the ADD thread regarding aripiprazole & selegiline specifically.

As such information regarding other MAOI's combined with selegiline would also be of use. It's a starting point if nothing else.

If anyone has any information anecdotal or otherwise it's appreciated. Since the information doesn't seem to appear in the literature hopefully someone else will be able to locate it or at least elucidate on the topic from personal or anecdotal experience.
Our thanks & gratitude go out to anyone able to provide any insight into or elucidate further regarding the topic in question.

Edited: Copy paste error. Changed the error to reflect that any information regarding MAOI's & selegiline is also appreciated.

 

[I_Hate_This_Place]

I don't prefer usage of selegiline with abilify becouse that will over activate D2 receptors which known to be the cause of must mental illness (ocd, schizophrenia, and the H in ADHD)
Links? My laptop is broken and she have the links so I can't provide them.

I know you say you don't have any links to literature regarding the subject but could you elucidate on your statement? I'm sorry to hear that your laptop is broken BTW! I hope that your laptop gets working again soon or that you find alternative in whatever manner best suits you.

As for your reply; my understanding is that the main concern with the usage of aripiprazole & selegiline are serotergenic as opposed to dopaminergic interactions? In particular SS as well as the potential for a hypertensive crisis. Though oddly enough there is literature indicating the potential for hypotension. That potential factor was also mentioned & discussed in the ADD thread. There is more information concerning my question in that thread. I link to it in my OP Aripiprazole (Abilify) & Selegeline / L-Deprenyl (Emsam) Interactions.

I can look at the literature myself. Which I shall. If you could; would you please elucidate further on the statement that "D2 receptors which known to be the cause of must (most?) mental illness". I'm familiar with the disorders that you mention but to the best of my knowledge there is a lot more to the disorders in question than over active D2 receptors. As an example the meta analysis of Glutamate and dopamine in schizophrenia: an update for the 21st century gives an example of some of the hypothesis of what is involved. I was under the impression that the full mechanisms involved where not known? That some mechanisms have been discovered but that there is still a lot we don't know.

Limitations of the dopamine evidence in schizophrenia
The findings reviewed above provide evidence that there is a dopaminergic abnormality underlying schizophrenia, localise it to presynaptic dopamine dysfunction and link this to the symptoms of the disorder. However there are a number of findings that remain inadequately accounted for. These are discussed below.

Treatment resistance and non-dopaminergic forms of schizophrenia
One third of individuals with schizophrenia do not respond to non-clozapine antipsychotics (Mortimer et al., 2010) despite high levels of D2 occupancy (Kapur et al., 2000). Furthermore they do not respond to manipulations that deplete presynaptic dopamine either (Remington et al., 2012). The implication is that for a significant number of patients the pathophysiological basis of their symptoms involves more than dopaminergic excess, or may be unrelated to dopaminergic dysfunction. Demjaha et al. have shown that dopamine synthesis capacity appears was raised in individuals with a treatment responsive illness but not in treatment resistant patients (Demjaha et al., 2012). This is in agreement with earlier findings that found increased synaptic dopamine was predictive of treatment response (Abi-dargham et al., 2000). Overall this suggests that there may be a ‘non-dopaminergic’ sub-type of schizophrenia (Howes and Kapur, 2014).

Negative and cognitive symptoms
Whilst dopaminergic dysfunction has been linked to negative and cognitive symptoms, and there are plausible mechanisms to explain this (as reviewed above), the direction of causality has yet to be established (Howes et al., 2012a). Furthermore, the challenge studies provide evidence that dopamine elevation, albeit to supra-physiological levels, reduces negative symptoms (Laruelle et al., 1999), which is not consistent with a simple model of presynaptic dopamine dysregulation underlying negative symptoms. This could be accounted for by the hypothesis that there are regionally selective changes, with low cortical dopamine accounting for negative and cognitive symptoms (Laruelle, 2014). However, this hypothesis remains to be tested with in vivo imaging studies, although this is now possible (Narendran et al., 2009; Narendran et al., 2014). Notwithstanding this, in clinical practice the effects of dopamine antagonists and partial agonists on cognitive impairments and negative symptoms are modest at best (Murphy et al., 2006), and may even worsen cognitive function(Kim et al., 2013b). This implies that either the dopamine modulating tools currently employed are blunt instruments or that other pathways, such as those involving glutamate, contribute to cognitive dysfunction.

Dual diagnosis
Substance dependence is common in people with schizophrenia (Buckley et al., 2009) and a number of studies have examined this population. Decreased amphetamine induced dopamine release has been demonstrated in dual diagnosis patients compared to healthy controls (Thompson et al., 2013). Similarly, in clinically high risk individuals those that were cannabis dependent showed reduced dopamine release (Mizrahi et al., 2013). Imaging of dopamine synthesis capacity in individuals who experience psychotic symptoms when they smoke cannabis showed significantly reduced striatal [18F]-DOPA uptake compared to healthy volunteers (Bloomfield et al., 2014). These findings indicate that the link between substance abuse and psychosis may involve a pathway that is distinct from the striatal presynaptic dopamine dysfunction described above.

I know that more work has occurred in the field since this analysis was done but I just wanted to give a quick example in the literature that indicates that there is more to mental illness than D2 receptor over activation. I'm aware that the "dopamine theory" is a contentious discussion but to the best of my knowledge even within said theory there is believed to be more involved than strictly D2? If I'm incorrect on this belief please do inform me of further information. The study I linked references schizophrenia specifically as that is the most relevant of the illnesses at this point that you mentioned in your statement.

As to the next mental illness in your statement OCD; again to the best of my knowledge OCD involves more than just D2 receptors? I'm aware than D2 receptors have been reported to be reduced in the striatum of some with OCD as well as both reduced & increased DAT binding. However to the best of my knowledge that is just a small part of a much larger clinical picture & is not the "cause" of OCD.

In the case of ADHD D2 dopamine receptor subtype-mediated hyperactivity and amphetamine responses in a model of ADHD as an example does seem to indicate that D2 is the primary receptor involved in that particular hyperactive sub-type of ADHD. There are definitely differences in the receptors involved as well many other factors between the 3 examples you mentioned. OCD, Schizophrenia & ADHD (Emphasis from Quote) are all mental illnesses but I don't see where D2 over activation is the "cause" of all three. As stated there are significant differences in the pathology of the three mental illnesses you mentioned in your statement.

As I said I'm thankful for any information regarding interactions between aripiprazole (or MAOI's in general) & selegiline but am at a bit of a loss as to what you are stating regarding D2's role in an interaction between aripiprazole & selegiline? Are you saying that there is an actual interaction? Or are you saying that due to the mechanisms involved that the combination of the medications will not be effective? As I just noticed you said you "don't prefer". The use of "prefer" seems to indicate as personal preference over an interaction risk but again I'm not positive as to if that's actually what your saying?

Perhaps I'm just misunderstanding what you're trying to say? As based on your statement it appear that perhaps English is not your first language or you are using translation software? My apologies if this is not the case but the grammar & choice of words made me question if maybe there was a language barrier?

I'm on the autism spectrum (Asperger's) & sometimes have communication issues. In this case I can't determine if I'm just misunderstanding what you're trying to say or if your statement is to vague for me to understand what you're trying to say? No offense intended in anyway BTW! I'm just confused.

If you could you please elaborate or reword your statement it'd be appreciated. Also if possible you may wish to peruse Aripiprazole (Abilify) & Selegeline / L-Deprenyl (Emsam) Interactions over in N&PD. (I tend to forget the name change & call it ADD )There is some more discussion in that thread.
As like I stated I posted this thread in this forum mostly in the hope that it would draw more attention to the thread in NP&D. Questions looking for journal articles & the like are often better suited to N&PD in general. However; in this case with the dearth of information regarding my question I'm hoping that perhaps someone reading this forum has had personal, anecdotal or other experience with the substances in question & can give any input whatsoever on the topic. At this point personal / anecdotal information is better than no information.

Thanks again for taking the time to post! Hopefully you (or someone reading that gets it?) can clarify & I can better understand what it is your trying to say.


Admittedly this study I'm linking is a bit dated but seems to serve it's purpose as an offhand example.

Again the study is dated but is being used for illustrative purposes & to the best of my knowledge nothing has been published that expressly contradicts the usage of these as examples of the involvement of more than D2.

Though research may have since been done that contradicts some of the information contained within these 2 studies I don't believe that anything has been discovered that invalidates these examples as evidence that more than D2 is involved with the mental illnesses mentioned in the statement made by ibtisam midlet.

 

[I_Hate_This_Place]

Like I have said before Aripiprazole is selective dopamine 2 partial agonist (Wikipedia)

Monoamine oxidaz B is the generator of MPP+ that is a toxic to dopamine 2 pathways
So Blocking monoamine oxidaz B will cause upregulation on D2 pathways
>>https://en.m.wikipedia.org/wiki/MPTP

and swim said that selegiline make him put more effort to complete task perfectly (ocd).

I'm quite familiar with the binding profile of aripiprazole as well as selegiline. I thought that was made clear in my posts in this thread & in my other thread Aripiprazole (Abilify) & Selegeline / L-Deprenyl (Emsam) Interactions. Apparently there is some sort of communication issue?

As I'm absolutely boggled as to what MPTP could possibly have to do with this discussion? We're not discussing Parkinsons research, herbicides or drug contamination...
I don't see how MPTP is remotely relevant to the conversation? MPTP is a neurotoxic metabolite of MPP+ but I don't see how that has any relevance to the discussion at hand? MPP+ does not occur naturally in the human body. I really am at a total loss as to what you're referring to?

It would appear there is some sort of communication issue though as your posts don't make sense in relation to the topic at hand. Thanks for trying but for some reason there appears to be a mix-up.

I'm glad that your laptop will be restored & that you have found medications that work for you though. (y)

 

[Harmredux]

You are a waterfall... just pouring out and go-go-go... brother, have you ever looked into Remeron? It sidesteps all that stuff and is gentle. OCD, impulsive behavior... low toxicity. Maybe I am overstepping here, but you seem to be going a mile a minute. I appreciate the academic strictness when it comes to making decisions. Just wondering if you looked at this as an option because without going into too much detail (one of the benefits of Remeron), I think it's at least worth a look for you.

 

[AlphaMethylPhenyl]

I don't prefer usage of selegiline with abilify becouse that will over activate D2 receptors which known to be the cause of must mental illness (ocd, schizophrenia, and the H in ADHD)
Links? My laptop is broken and she have the links so I can't provide them.

No, not really. In practice, selegiline at least in the form of EMSAM (transdermal decreasing m-amp and amp metabolites) doesn't really exacerbate psychotic illness. I mean it could, but not in all cases as something like THC would.

Aripiprazole is selective D2 D3 partial agonist
See just from Wikipedia >>https://en.m.wikipedia.org/wiki/Aripiprazole

Selegiline is selective monoamine oxidaz B inhibitor which it's first target is dopamine.

Must of pathways end with dopamine, it's the main chemical that is represent every nice feeling you could feel, she are known to be implicated in schizophrenia, but she is the main couse of ADHD. And the last pathway in ocd ( I was have it), and now I'm completely free of ocd by using respiridon as a D2 selective powerful antagonist and anafranil as Serotonin reuptake inhibitor which known to down regulate dopamine 2 pathways (no links I know)

Aripiprazole has a host of effects on various receptors, but yes the main idea is D2 partial with low efficacy. Important is the atypical norm of 5-HT2a antagonism.

Selegiline really only works for depression when it inhibits MAO-A.

Never heard that SSRIS "down regulate" D2. The best explanation I've found is BDNF activity in the hippocampus and less in the amygdala.

Monoamine oxidaz B is the generator of MPP+ that is a toxic to dopamine 2 pathways
So Blocking monoamine oxidaz B will cause upregulation on D2 pathways
>>https://en.m.wikipedia.org/wiki/MPTP

and swim said that selegiline make him put more effort to complete task perfectly (ocd).

?

Could be OCD, could be something else. But MAOIs are widely effective for forms of mental illness, so there's no promise that OCD is the culprit.

 

[I_Hate_This_Place]

You are a waterfall... just pouring out and go-go-go... brother, have you ever looked into Remeron? It sidesteps all that stuff and is gentle. OCD, impulsive behavior... low toxicity. Maybe I am overstepping here, but you seem to be going a mile a minute. I appreciate the academic strictness when it comes to making decisions. Just wondering if you looked at this as an option because without going into too much detail (one of the benefits of Remeron), I think it's at least worth a look for you.

Thanks for the advice but I'm asking in regards to the conditions my wife suffers from not myself. I'm on the autism spectrum myself (Aspergers) & my extraordinarily verbose writing style is to the best of my knowledge just one of my personality quirks. I have a tendency to restate my point multiple times. I will state the same information just in a different manner than I had previously. I will just vary or re-word the way in which I deliver said information in an attempt to be sure that despite any issues the intended recipient may have in understanding the information that I'm trying to convey they end up understanding at least one of the attempts I've made to convey said information. I'm well aware that I do so & that my posts may come off as someone who is either quite stimulated or perhaps manic. I'm in fact neither of those things but I totally understand how my posts could be misconstrued as they do appear that way to the general observer.

There's also the the fact the in general I enjoy language. In terms of how those on the "spectrum" are described I would likely fall into what some describe as a 'verbal' sub-type but I digress. Regardless the questions I'm asking do not pertain to my own mental health. They pertain to my wife's. I don't have any concerns for my mental health in terms of what you were suggesting might be the case. As an aside I've helped to treat someone with OCD using CBT resulting in a remission of symptoms so I'm quite familiar with that particular condition. No worries or offense taken to your suggestion BTW. As I mentioned I understand completely how my posts could appear to indicate such things to the general observer. Those that are familiar with me via this account or my old one are aware of this particular quirk.

Besides maybe I just enjoy hearing myself talk!

Though coincidentally enough I do happen to take mirtazapine (Remeron). In my case I consume the substance in a low dose more as an appetite stimulant & sleep aid than for it's antidepressant type activity despite mirtazapine being classified as a TeCA. It's quite possible that mirtazapine may in fact help to improve my mood but if so that effect is a secondary one. In terms of the reasoning behind my consumption of the substance the aforementioned effects on appetite & sleep are primary. I'm digressing from my original topic though & veering completely off from my initial subject matter to answer your post so I'm going to call it answered & move on.

Either way TL;DR as of this point we are proceeding in a different direction with my wife's treatment & this topic is no longer relevant to that direction. Considering that fact this thread can be closed.

 

[Harmredux]

Well heck, I didn't even charge you for an office visit. I am so very wordy, I apologize for writing more than reading , didn't realize it was your wife.
My wife is crazy but I take the drugs to deal with it. Work it out however ya gotta.