Aricept for Bipolar

[WisNeuro]

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Pt today came in today, 50yo, was prescribed Aricept years ago by her psychiatrist to help with her Bipolar disorder. Is this a thing that I am not aware of, or just a terrible prescribing practice?

 

[whopper]

It suggests the psychiatrist doesn't know what they're doing.

On occasion patients get a reaction to a med that defies the scientific data. Actually makes sense when you think of biology always having outliers. In such cases I heavily document why I'm continuing the patient on the medication that's appearing to have benefits outside of it's usual scope. (E.g. I have a patient with depression-just depression and the only medication that worked is Ziprasidone, not as an augmentation agent but working as an antidepressant itself. She tried over 10 antidepressants with no benefits and several side effects. She's never been manic or hypomanic. Stopping the Ziprasidone caused her to be depressed again, restarting it caused the depression to go away. She's the only patient I've seen where this happen and I documented why she's on it for depression).

But when I see this going on it's more often the other doctor not knowing what they're doing, nor documenting the odd reaction which doesn't help other providers clear up what's going on. Notes are supposed to be written in a manner so that the practitioner but other providers will be able to understand what was going on and take over care if need be.

And BTW unless the patient has a deficiency of acetylchoine Aricept shouldn't cause any improvement. Studies show when people want cognitive benefits and try it it doesn't help and actually causes problems. There was a study done where a bunch of students tried it and none of them performed better. Makes sense cause Aricept only helps where there's a deficiency of Acetylcholine and adding more when the person has enough doesn't help. I've seen some TBI patients where Aricept helps but it makes sense there Not surprising that someone with a TBI might be producing less acetylcholine.

 

[WisNeuro]

Yeah, I am looking for notes that justify the prescription and am so far coming up empty. Heck, even in conditions where there is a decrease in acetylcholine, the med does not work, as in the AD trials.

 

[st2205]

Hey, at least it’s not disulfiram for acute mania.

 

[birchswing]

I don't know what a sigma-1 receptor is. But if there is a link between Aricept and bipolar, I'm guessing that's it. Even if it's just a link someone wanted to make theoretically. Sometimes people don't even bother to make a plausible link.

Sigma-1 seems to be the new buzz, esp with Nuedexta being prescribed off-label for a menagerie of disorders.

I'd be curious whether the Aricept was prescribed for bipolar before it became available as a generic.

 

[clausewitz2]

There are a few small (and I do mean small) studies out there that claim to demonstrate some benefit in bipolar disorder for patients who were non-responders to lithium and depakote, mostly in reduction of manic symptoms. This is the most interesting one: Donepezil in treatment-resistant bipolar disorder - ScienceDirect . It seems like not an absolutely insane third or fourth-line treatment approach for the sort of bipolar folks who have been depressed like once ever and mostly get manic on a very regular basis. Probably not at all useful for the sort of bipolar folks who got hypomanic/manic like once ever and mostly get depressed on a very regular basis. Can't find any similar data for aricept.

So basically either the person prescribing this is someone with a very deep knowledge of essentially speculative approaches to managing treatment-resistant bipolar disorder, or they are a muppet as whopper suggests.

 

[WisNeuro]

There are a few small (and I do mean small) studies out there that claim to demonstrate some benefit in bipolar disorder for patients who were non-responders to lithium and depakote, mostly in reduction of manic symptoms. This is the most interesting one: Donepezil in treatment-resistant bipolar disorder - ScienceDirect . It seems like not an absolutely insane third or fourth-line treatment approach for the sort of bipolar folks who have been depressed like once ever and mostly get manic on a very regular basis. Probably not at all useful for the sort of bipolar folks who got hypomanic/manic like once ever and mostly get depressed on a very regular basis. Can't find any similar data for aricept.

So basically either the person prescribing this is someone with a very deep knowledge of essentially speculative approaches to managing treatment-resistant bipolar disorder, or they are a muppet as whopper suggests.

I was just doing a lit review as you posted. I found a recent meta-analysis that found no effect of Aricept, galantamine, or memantine in Bipolar
Acetylcholinesterase inhibitors and memantine in bipolar disorder: A systematic review and best evidence synthesis of the efficacy and safety for multiple disease dimensions - ScienceDirect

Also, some possibility (albeit scant evidence) of donepezil induced mania in AD patients going through up-titration
Donepezil-associated manic episode with psychotic features: a case report and review of the literature - ScienceDirect

 

[clausewitz2]

I was just doing a lit review as you posted. I found a recent meta-analysis that found no effect of Aricept, galantamine, or memantine in Bipolar
Acetylcholinesterase inhibitors and memantine in bipolar disorder: A systematic review and best evidence synthesis of the efficacy and safety for multiple disease dimensions - ScienceDirect

Also, some possibility (albeit scant evidence) of donepezil induced mania in AD patients going through up-titration
Donepezil-associated manic episode with psychotic features: a case report and review of the literature - ScienceDirect

I think it is safe to say that the evidence is far from overwhelming for this being a useful approach. That said, I am always sensitive to the notion that particular endophenotypes of ostensibly the same DSM disorder may actually have a significant benefit from a medication that is not shared by most people with the diagnosis, and so will be wiped out in most large samples. We see this with neuroleptics with a population of folks who kinda sorta maybe improve with them and don't separate all that well from placebo but then a group of 10% or so who get dramatically better. Of note if used indiscriminately this is also an excellent justification of all manner of quackery, and I recognize that, but unfortunately reality is messy and it is hard to formulate a deontologically satisfying rule here.

 

[WisNeuro]

I think it is safe to say that the evidence is far from overwhelming for this being a useful approach. That said, I am always sensitive to the notion that particular endophenotypes of ostensibly the same DSM disorder may actually have a significant benefit from a medication that is not shared by most people with the diagnosis, and so will be wiped out in most large samples. We see this with neuroleptics with a population of folks who kinda sorta maybe improve with them and don't separate all that well from placebo but then a group of 10% or so who get dramatically better. Of note if used indiscriminately this is also an excellent justification of all manner of quackery, and I recognize that, but unfortunately reality is messy and it is hard to formulate a deontologically satisfying rule here.

I totally get the whole idea that if a patient has not really been helped by the first several lines of treatment, it's generally ok to start strongly considering off label meds. But, from this person's med history, they were just started on a combo of donepezil, trileptal, and queitiapine from the get go following a bad manic episode.

 

[clausewitz2]

I totally get the whole idea that if a patient has not really been helped by the first several lines of treatment, it's generally ok to start strongly considering off label meds. But, from this person's med history, they were just started on a combo of donepezil, trileptal, and queitiapine from the get go following a bad manic episode.

That combo as the initial approach does seem dispositive in favor of the muppet hypothesis.

 

[Liquid8]

Have never heard anything like this.

This sounds like one of those cases where it would be easier to pick up the phone and just ask the prescriber what their reason for prescribing Aricept was.

 

[WisNeuro]

Have never heard anything like this.

This sounds like one of those cases where it would be easier to pick up the phone and just ask the prescriber what their reason for prescribing Aricept was.

That's usually what I try. However, this was a prescriber outside of our system, and doesn't even practice in the state anymore. Prescribers who took over after that apparently didn't feel like messing with the medications too much.

 

[whopper]

This is exactly why I state that the current state of practice of of an unacceptable amount of physicians is ridiculous.

More than half the time I call another doctor's office I can't get a hold of the other physician.

You would expect an average doctor to document the effects of each medication very well.

From my own experience it seems that this is less than 1/3 of the physicians I see.

So if the expected average is to just write decent notes, and it turns out the average doesn't even do that what type of opinion am I supposed to have?

When I get other doctor's notes it's usually to the effect of "prescribe medication X 10 mg"
Then next note: "stop medication x" with no writing on the rationale or the effects the medication had on the patient.

And this is assuming I can even understand the doctor's handwriting or the doctor even gave me the notes. Less than 1/2 the time I don't get them at all unless my assistant and I pester the other doctor's office or hospital multiple times.

Which bring me to the next unacceptable yet commonly held thing going on. I get records less than half the time despite that federal law states they must be given if requested by the patient unless the institution is owed money by the patient or they have good reason to believe that by giving the notes it'll cause physical harm to someone else. So again if it turns out less than half are not doing the expected legal minimum, what opinion am I supposed to have?

Oh well. This is the norm in the real-world practice yet I see no initiatives by organizations like the AMA or the government to fix this.

 

[WisNeuro]

Which bring me to the next unacceptable yet commonly held thing going on. I get records less than half the time despite that federal law states they must be given if requested by the patient unless the institution is owed money by the patient or they have good reason to believe that by giving the notes it'll cause physical harm to someone else. So again if it turns out less than half are not doing the expected legal minimum, what opinion am I supposed to have?

I only occasionally have a problem getting previous notes/reports. Although I'm usually only needing previous neuropsych reports, neurology notes, or an ED admission for some sort of brain-related incident. My assistant usually gets these fairly easily. But, for some people, who do not respond to us, or drag it out, I just send a long the relevant snippet about medical records and state that if I do not receive them, I will be making a complaint to the relevant board for their specialty. I only have to do that about once or twice a year for what I need, and so far it has always resolved the issue pertaining to records I need.

 

[whopper]

What I do it just point-blank tell the patient what's going on. If the other physician dodged my call once I will tell the patient the doc is a human being, maybe it was an honest mistake, but after a clear pattern of 3 or more, I tell the patient "it is what it is." "It's not my intent to bash anyone but it is what it is and I have tried to contact him or her three times." I've even gone as far as tell the patient they ought to complain to the state medical board if it went beyond that and unfortunately this is not rare for me.

If a doctor or other provider is very communicative I tend to refer to them more but I still have quite a smorgasbord of providers difficult with communications.

Medical records at several of the local hospitals are about as bad. On some occasions the patient had to physically go to the hospital and demand the records be given to them while there because of multiple failures in attempting to get them by fax.

 

[WisNeuro]

I will say, having an assistant makes me getting requests for my records much faster. When someone can go pull the files, I can quickly confirm it, and she can fax it off for me, we usually get them out same day, never more than 48 hours. Unless I am on vacation. But yeah, there should be better enforcement about getting records where they need to go for efficient and accurate patient care.

 

[Liquid8]

Prescribers who took over after that apparently didn't feel like messing with the medications too much.

That is also sad to hear. Surely if something doesn't make sense, it is the new treating doctor's responsibility to re-evaluate the suitability and effectiveness of all prescribed medication. One has to be aware of their limitations obviously, but if something was like Aricept was being prescribed at a low dose it wouldn't be difficult to reduce it or cease it, or if it was at a high dose to refer to a psychogeriatrician for a second opinion.

When I get other doctor's notes it's usually to the effect of "prescribe medication X 10 mg"
Then next note: "stop medication x" with no writing on the rationale or the effects the medication had on the patient.

When I'm discussing changing or adding medications I always find myself flicking through the file with patients to see what I've tried them on before and why things were ceased. There are obvious benefits to efficient decision making, and if I'm thinking about deciding whether to trial a drug again it makes bloody big difference if someone had anaphylaxis compared to some one who had mild GI upset and quit after a single day. Have no idea how one could practice without documenting this kind of stuff!

 

[WisNeuro]

That is also sad to hear. Surely if something doesn't make sense, it is the new treating doctor's responsibility to re-evaluate the suitability and effectiveness of all prescribed medication. One has to be aware of their limitations obviously, but if something was like Aricept was being prescribed at a low dose it wouldn't be difficult to reduce it or cease it, or if it was at a high dose to refer to a psychogeriatrician for a second opinion.

It's the 10mg dose. And, this person isn't at the level of needing a psychogeriatrician yet, they're only 50! That's a young patient in my usual population.

 

[clausewitz2]

Have no idea how one could practice without documenting this kind of stuff!

Badly, in a system that does nothing to incentivize good practice of the relevant kind.

 

[Liquid8]

It's the 10mg dose. And, this person isn't at the level of needing a psychogeriatrician yet, they're only 50! That's a young patient in my usual population.

My view is that in this scenario this medication should be stopped, as it's not indicated for the patient or the condition. I don't think it's particularly ethical to leave a patient on a medication that you know is probably not having any clinical benefit while potentially leaving them at risk of having side effects or interactions.

On the other hand, If someone is hesitant to make such a change in treatment because they're not sure (or if they just don't know what they're doing as is probably the case with your patient), they should definitely be looking at a second opinion or at the least running it by a colleague. In most instances a general psychiatrist would be fine, but a psychogeriatrician would be more experienced at dealing with Alzheimer's medications which is why I'd consider it if a patient was on a very high amount. If the psychiatrists haven't been inclined to change anything and are continuing to prescribe in a way that appears to be out of keeping with the expected standard of clinical practice, I don't really know what else can be done.