Pt case: invega works but risperdal really doesn't. Any similar cases?

[caxoo]

As stated, interesting situation where invega is the only thing that has worked well, but risperdal surprisingly is one of the worst ones for the pt

Any similar cases/thoughts and comments as to why? Do the other risperdal metabolites really have that much variation in clinical effects? Or is it likely moreso the difference in pharmacokinetics

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[Nudexta]

In notice that invega is superior to risperdal which I don’t know why. This is just based on the clinical experience

 

[clausewitz2]

A big factor is the paliperidone doesn't undergo hepatic metabolism while risperidone does. Also has some differences in H1 occupancy (probably less sedating) and dissociates faster from D2 receptors than risperidone does (by at least a couple orders of magnitude) so putatively possible less EPS. Finally it also has essentially no muscarinic activity whereas risperidone definitely does, so if someone is sensitive to that I can imagine them feeling much less unpleasantly out of it/disoriented on equivalent dose of paliperidone as compared to risperidone.

Also the name is different and the patient knows this. Never to be underestimated.

EDIT: low impact journal, but this is interesting: Comparative Pharmacology of Risperidone and Paliperidone

 

[ObsequiousAplomb]

I have not seen oral Invega to be any more effective than oral Risperdal, though I have heard anecdotally that some people find it that way. I have also heard anecdotes of the opposite.

As to my anecdote, our state hospital was only allowing Risperdal Consta for a long time due to cost issues. We only had three LAIs on formulary: Consta, Haldol dec, and Prolixin Dec. If a patient didn't want Haldol or Prolixin (usually because of the very high dosing) and they were involuntary medication approved, their only real option was Consta or Dec.

I led the push in the P&T committee to add Invega Sustenna to the formulary. At first we would keep just oral Risperdal, as oral Invega costs a lot more and is only in that delayed release version. With a few of the initial poor responders to Consta

Before patients ended up getting unusual regimens of Consta, we obtained serum levels prior to going above 50 q2weeks or in some instances going 25q2weeks and 50q2weeks on alternating schedules. All of the levels of the people who were partial or minimal responders at 50q2weeks who did respond to a later unusual regimen had serum levels that were minimal or nil Risperdal and appropriate levels of Invega.

When it comes to Sustenna, I have found that it is often but not always preferred by patients because they only need to take it once a month. It also hurts less, I hear. Other patients prefer the closeness of seeing their team twice a month. Some patients had major decompensation with the transition off of Consta. Staff and patients tended to be happier with the wider dosing intervals, as it cut the number of physical holds and altercations related to involuntary meds considerably.

Some of the doctors (and more often the nurses) didn't like the idea of giving PO Risperdal and IM Invega as they felt it was polypharmacy. Despite showing the information on the manufacturer website and the FDA label that it is in fact recommended and safe to start with PO Risperdal for cost reasons, the P&T Committee caved and added PO Invega. Costs went up, and some staff were satisfied.

 

[mojetter]

Before patients ended up getting unusual regimens of Consta, we obtained serum levels prior to going above 50 q2weeks or in some instances going 25q2weeks and 50q2weeks on alternating schedules. All of the levels of the people who were partial or minimal responders at 50q2weeks who did respond to a later unusual regimen had serum levels that were minimal or nil Risperdal and appropriate levels of Invega.

fascinating! Can you clarify this, what is the unusual regimen? ..50mg q2weeks had a nil or minimal risperdal level?

 

[ObsequiousAplomb]

There were patients taking Risperdal 6 qhs, Consta 50 q2weeks, and we got serum levels before the 3rd or 4th injection. Many of them were just taking the Consta though, since we didn't do involuntary PO antipsychotics. Like I said, their levels were either no Risperdal or very, very low Risperdal, but a reasonable amount of Invega. I just assumed they had a rapid polymorphism for that step of metabolism.

Since we didn't have Sustenna, Maintenna, or Reprevv on formulary, if they couldn't take Haldol Dec and they still met involuntary med criteria (a very high bar) we would have to make a reasonable petition to the involuntary med approval committee. That's why we were getting the levels, so that at our 3rd monthly committee meeting for the patient we could have some data. If it showed they really were still subtherapeutic, we could justify getting fancy with the Consta.

Some patients ended up taking 50 qweek, others 50/25 qweek, and others still 67.5 or even 75 q2weeks. Whatever fancy thing we were doing, we had to back it up with a real reasoning and the patient had to really improve with the fancy regimen.



This state hospital had a ton of severely refractory patients as well. Sometimes you would look at a regimen like Seroquel 1200 qhs, Haldol Dec 300 q3weeks, Consta 50 q2weeks, and Zyprexa 20 BID (plus or minus depakote, lithium, Lamictal, etc) and rightfully be very annoyed. But if you read the notes you would see several years worth of PANSS, CGI, AIMS, etc, and very thorough documentation. Sometimes the patients were there for 50+ years and it really was clearly documented that despite them clearly still being psychotic it was a substantial improvement.

Still, I very frequently wondered why the reluctance by the staff to administer clozapine won out in the decision between four maximally dosed antipsychotics and one reasonably dosed one. Sometimes it was because there really had been a real trial of clozapine or a severe adverse effect that recurred on a second trial (myocarditis, etc).

It really helped that we only did monthly notes so there were fewer notes to comb through and the residents and fellows felt compelled to document that way. If you only have one note due in a day, it's usually a well-written one. No templates or silly EHR radio buttons, just good old fashioned paragraphs. Charts documenting behavior trends for catatonic patients, lists of violent outbursts and a nice summary statement describing the patterns for the past 10-15 of them. Same thing with the attending reviewing your notes. If your MSE didn't accurately describe patterns of behavior and thought patterns based on 10+ interviews over 4 weeks, they had plenty of time to give you detailed feedback.

Of course, other times, on other continuing treatment units (the ones without residents rotating through), you would see the same regimen but without the records. It all depends on the patients' legal status and their own desires to be medicated.

There's also the major drawback to having 12 months of state hospital psychiatry with no 24 hour call: we did a lot fewer admissions those 12 months than many peers at other programs. Almost made up for it at the private for profit hospitals we rotated through.

 

[clausewitz2]

There were patients taking Risperdal 6 qhs, Consta 50 q2weeks, and we got serum levels before the 3rd or 4th injection. Many of them were just taking the Consta though, since we didn't do involuntary PO antipsychotics. Like I said, their levels were either no Risperdal or very, very low Risperdal, but a reasonable amount of Invega. I just assumed they had a rapid polymorphism for that step of metabolism.

Since we didn't have Sustenna, Maintenna, or Reprevv on formulary, if they couldn't take Haldol Dec and they still met involuntary med criteria (a very high bar) we would have to make a reasonable petition to the involuntary med approval committee. That's why we were getting the levels, so that at our 3rd monthly committee meeting for the patient we could have some data. If it showed they really were still subtherapeutic, we could justify getting fancy with the Consta.

Some patients ended up taking 50 qweek, others 50/25 qweek, and others still 67.5 or even 75 q2weeks. Whatever fancy thing we were doing, we had to back it up with a real reasoning and the patient had to really improve with the fancy regimen.



This state hospital had a ton of severely refractory patients as well. Sometimes you would look at a regimen like Seroquel 1200 qhs, Haldol Dec 300 q3weeks, Consta 50 q2weeks, and Zyprexa 20 BID (plus or minus depakote, lithium, Lamictal, etc) and rightfully be very annoyed. But if you read the notes you would see several years worth of PANSS, CGI, AIMS, etc, and very thorough documentation. Sometimes the patients were there for 50+ years and it really was clearly documented that despite them clearly still being psychotic it was a substantial improvement.

Still, I very frequently wondered why the reluctance by the staff to administer clozapine won out in the decision between four maximally dosed antipsychotics and one reasonably dosed one. Sometimes it was because there really had been a real trial of clozapine or a severe adverse effect that recurred on a second trial (myocarditis, etc).

It really helped that we only did monthly notes so there were fewer notes to comb through and the residents and fellows felt compelled to document that way. If you only have one note due in a day, it's usually a well-written one. No templates or silly EHR radio buttons, just good old fashioned paragraphs. Charts documenting behavior trends for catatonic patients, lists of violent outbursts and a nice summary statement describing the patterns for the past 10-15 of them. Same thing with the attending reviewing your notes. If your MSE didn't accurately describe patterns of behavior and thought patterns based on 10+ interviews over 4 weeks, they had plenty of time to give you detailed feedback.

Of course, other times, on other continuing treatment units (the ones without residents rotating through), you would see the same regimen but without the records. It all depends on the patients' legal status and their own desires to be medicated.

There's also the major drawback to having 12 months of state hospital psychiatry with no 24 hour call: we did a lot fewer admissions those 12 months than many peers at other programs. Almost made up for it at the private for profit hospitals we rotated through.

Fascinating, really makes me wish that the state I trained in hadn't shut down the local state hospital a few years before I started so i could have at least seen this sort of environment in training. Sort of proper old-school asylum type psychiatry.

For some of these folks on multiple LAIAs, did you all ever try somewhat less traditional agents like minocycline or sarcosine? I don't doubt some of these people may have gotten genuinely a bit better but once you get into the evidence-free land of Consta + haldol dec, etc., it seems like hammering D2 over and over is going to have limited returns and something like minocycline isn't -less- evidence-based.

 

[jbomba]

A big factor is the paliperidone doesn't undergo hepatic metabolism while risperidone does. Also has some differences in H1 occupancy (probably less sedating) and dissociates faster from D2 receptors than risperidone does (by at least a couple orders of magnitude) so putatively possible less EPS. Finally it also has essentially no muscarinic activity whereas risperidone definitely does, so if someone is sensitive to that I can imagine them feeling much less unpleasantly out of it/disoriented on equivalent dose of paliperidone as compared to risperidone.

Also the name is different and the patient knows this. Never to be underestimated.

EDIT: low impact journal, but this is interesting: Comparative Pharmacology of Risperidone and Paliperidone

My understanding was risperdal had virtually no anti cholinergic activity. I just checked some receptor affinity charts which seemed to confirm this. Are you seeing something different?

 

[clausewitz2]

My understanding was risperdal had virtually no anti cholinergic activity. I just checked some receptor affinity charts which seemed to confirm this. Are you seeing something different?

You are of course completely correct. Slip of the keyboard on my part, I meant alpha-adrenergic activity (risperidone antagonizes alpha-adrenoreceptors much more strongly than paliperidone does).

 

[Sikrouf]

You are of course completely correct. Slip of the keyboard on my part, I meant alpha-adrenergic activity (risperidone antagonizes alpha-adrenoreceptors much more strongly than paliperidone does).

You sure about that i though the orthostatic hypotension from pali was higher thats why some countries didnt bother with the oral formulation

 

[clausewitz2]

You sure about that i though the orthostatic hypotension from pali was higher thats why some countries didnt bother with the oral formulation

I am seeing conflicting sources so now am genuinely unsure. Probably not the reason the patient in OP's post did better with it anyway.

 

[Sikrouf]

There were patients taking Risperdal 6 qhs, Consta 50 q2weeks, and we got serum levels before the 3rd or 4th injection. Many of them were just taking the Consta though, since we didn't do involuntary PO antipsychotics. Like I said, their levels were either no Risperdal or very, very low Risperdal, but a reasonable amount of Invega. I just assumed they had a rapid polymorphism for that step of metabolism.
.

At steady state risperidone/hydroxy risperidone is around 1/10 for extensive 2d6 metabolisers so thats quite normal

 

[ObsequiousAplomb]

Fascinating, really makes me wish that the state I trained in hadn't shut down the local state hospital a few years before I started so i could have at least seen this sort of environment in training. Sort of proper old-school asylum type psychiatry.

For some of these folks on multiple LAIAs, did you all ever try somewhat less traditional agents like minocycline or sarcosine? I don't doubt some of these people may have gotten genuinely a bit better but once you get into the evidence-free land of Consta + haldol dec, etc., it seems like hammering D2 over and over is going to have limited returns and something like minocycline isn't -less- evidence-based.

I agree, very much of what we were doing at the end of the algorithm wasn't evidence based but more likely institutional dogma.

Each attending and unit would try some interesting things. One of them loved to give everyone who was truly treatment-refractory B vitamins, Omega-3, NAC, etc.

We also were a very psychoanalysis and psychodynamic-centered program. All patients would have 4 or more hours of group therapy 5 days a week. Many/most would get individual therapy. So if a patient were too overmedicated/sedated to attend psychotherapy, we would usually have to back off. The preference was that someone be under medicated if it meant they would be more able to participate in psychotherapy.

One patient successfully petitioned to not receive involuntary meds because he felt even low doses made him too tired to pray the 40 times a day that he wanted to. Very interesting cases. Not very EBM though, I'll admit.