Complicated cross-titration assistance

[Slingshot]

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I was hoping to pick your brains on a situation I have not had before (I am a out of residency 8 months.)

I basically took over care of a 52 year old lady with long-standing Bipolar 1 with over 5 inpatient hospitlizations but has been out of the hospital for 7 years doing well in terms of not needing the hospital but is having signifigant weight gain, diabetes and obesity after being on 50mg of Consta every two weeks in addition to 2mg oral risperdal. Also on 2mg ativan at bedtime.

She has never been psychotic, only severe mania multiple times in the past. Current euthymic and for health concerns I am wanting to switch her regimen to monotherapy traditional mood stabilizer and at this point deciding on Tegretol due to hopefully most weight-neutral compared to depakote (She is a rapid cycler traditionally and at baseline is still pretty hypomanic so Lithium was lower on my list. Not to mention she already has diabetes and protein in her urine).

Anyway the question is how to get her from her risperdal to the tegretol. Will keep the ativan for now and later deal with that if necessary.

Another note. Consta was used because compliance of pills was an issue for her. However she now has nursing come twice daily to administer pills so orals are now an option

Tentative plan was to-
1-Stop the consta (so no further shots at this point and let that slowly self taper)
2-Continue the oral 2mg risperdal
3.Titrate tegretol up to monotherapy dose over the course of a couple of weeks

Leave her for 2 months on the tegretol and oral 2mg risperdal and than after months start cutting out a 1mg of risperdal each month for 2 months until off of it.

Knowing the entire time the Tegretol will be metabolizing the risperdal down steadily is the only thing that concerns me that is this "too" quickly? Since there is no pressing issue other than more long-term health, I am in no huge rush.

Alternatively whether or not induction of risperdal really matters given it simply increasing effective iloperidone levels (essentially invega) I do not think anyone is sure if induction of risperdal metabolism really even matters in any case.

Any better thoughts? Taper the consta more slowly? I believe it stays at steady state for 3-4 weeks after last injection and then ultimately takes 3 months to essentially be "gone."

Any tips would be really helpful!

 

[vistaril]

if you've made the decision to do it using Tegretol(another thread onto itself), the way you're doing it seems perfectly reasonable.....if anything I would pull the oral risperdal off faster. I certainly wouldn't give her a taper of a depo.

 

[Slingshot]

Hey I am open to better regimens! Basically goal is longer-term health benefits and weight loss.

I have gotten her a personal trainer and nutritionist in the home regularly and doing other non-medication stuff but wanted to do the "healthiest" medicine regimen now that she has resources like home health for compliance.

I guess tegretol, depakote or geodon were my 3 "healthiest" choices and figured tegretol is the "healthiest" given her age etc.

Open to better suggestions for sure! Remember never been psychotic if that matters! Also as mentioned has history of documented rapid cycling.

 

[IAmAUser]

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[Slingshot]

I definetly agree there are some patients who simply do so well on a certain medicine that it is in their best interest to live with the side-effects.

This case is not that way however given risperdal was used simply because med compliance was an issue and obviously risperdal consta is the cheapest long-acting and first choice if you are going long-acting for many people. This patient now has access to home health nurses to give her oral pills so she can now try many other medications she has never been on or was not able to be compliant with.

I hope in residency where you are at they are not practicing adding topomax to regimens for weight loss? I would advise you during residency to really stick with evidence based regimens and not necessarily go by what you have "seen" work. You actually start to create your own bias.

For example (and I am not a huge fan of tegretol) but if in your few short years of residency you have not seen good results and thus never use it, than you will continue to probably only end up using it as a last choice in patients when you try other ones you had "good" luck with. So by default you end up only using it on treatment resistant patients who are already unlikely to respond and thus propogating your view.

I definetly recomend you try to use every evidenced based treatment equally throughout residency and when you are done you can stick to your favorite.

Another point just for education sake. Antipsychotics cause diabetes by mechanisms other than simply causing obesity. So if someone who has gotten diabetic on anti-psychotics loses weight, it helps and often eliminates the diabetes but definetly not always.

There is also the issues of a black box warning for antipsychotics in elderly patients so when you have some on the cusp of their 60's, legally you are better served using something with no black box warning if it is potentially equally effective.

Just a few reasons why I am proceeding with the change.

The other thought I had was to simply lower the consta dose for 2 shots. Do one 37.5 mg shot, than a 25mg shot and then stop.

Any other thoughts?

 

[whopper]

It's hardly ever a good idea for someone to be on a benzodiazepine long-term.

As for the titration, the bottom-line is there's no way to tell until you try it or if you know for a fact that carbamazepine worked well in this patient.

The medical data only suggests that psychotropics will more likely work than not. We really only know if it'll work when we try it on the patient. It's possible to cross-titrate a patient to a medication that will not work though it's not the doctor's fault if the patient was never tried on that med and there was good reason to believe it could've worked well. Just make sure you warn the patient and let them know what they're getting into.

As for carbamazepine, it's cheap, but I prefer oxcarbazepine because it has less side effects though it is more expensive.

 

[IAmAUser]

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[whopper]

Just want to point out to not lock yourself into everything you learn in residency. Most of my experience in residency was inpatient or emergency psych. In office-based practice, I've seen a lot of patients do very well on Lamictal and that's something you'll hardly see on an inpatient unit or an emergency center.

Doing only one form of clinical practice can put blinders on you.

 

[vistaril]

I definetly agree there are some patients who simply do so well on a certain medicine that it is in their best interest to live with the side-effects.

This case is not that way however given risperdal was used simply because med compliance was an issue and obviously risperdal consta is the cheapest long-acting and first choice if you are going long-acting for many people. This patient now has access to home health nurses to give her oral pills so she can now try many other medications she has never been on or was not able to be compliant with.

I hope in residency where you are at they are not practicing adding topomax to regimens for weight loss? I would advise you during residency to really stick with evidence based regimens and not necessarily go by what you have "seen" work. You actually start to create your own bias.

For example (and I am not a huge fan of tegretol) but if in your few short years of residency you have not seen good results and thus never use it, than you will continue to probably only end up using it as a last choice in patients when you try other ones you had "good" luck with. So by default you end up only using it on treatment resistant patients who are already unlikely to respond and thus propogating your view.

I definetly recomend you try to use every evidenced based treatment equally throughout residency and when you are done you can stick to your favorite.

Another point just for education sake. Antipsychotics cause diabetes by mechanisms other than simply causing obesity. So if someone who has gotten diabetic on anti-psychotics loses weight, it helps and often eliminates the diabetes but definetly not always.

There is also the issues of a black box warning for antipsychotics in elderly patients so when you have some on the cusp of their 60's, legally you are better served using something with no black box warning if it is potentially equally effective.

Just a few reasons why I am proceeding with the change.

The other thought I had was to simply lower the consta dose for 2 shots. Do one 37.5 mg shot, than a 25mg shot and then stop.

Any other thoughts?

It's a tough call for me because the ideal treatment first line mood stabilizer based on ebm for maintenance in a rapid cycling bipolar pt is Depakote.

Is the possible weight gain from depakote worth this over the less common side effects of Tegretol considering that Depakote is standard treatment here and there is superior evidence for depakote's efficacy in this situation? I don't know....that's why it is a judgement call.

 

[Slingshot]

I hope you know how to spell topamax. And it does have some good evidence actually for weight loss.
http://www.nature.com/oby/journal/v11/n6/abs/oby2003102a.html
http://www.nature.com/oby/journal/v12/n10/abs/oby2004206a.html



That's true and a reasonable point, I'd also point out though, in the interests of evidence based medicine, that tegretol has no fda indication for any phase of bipolar illness, and the good evidence that does exist is for acute treatment of mania, not for maintainence (as you propose to use it) or for bipolar depression.

Tegretol actually is FDA approved for acute manic/mixed episodes in bipolar disorder. I agree there is no indication for maintence and prevention of symptoms in bipolar disorder but if you take a look at a great couple pages from the APA psychopharm book they list every tegretol study available and really comes out as well as any other tested medicine for this indication. But not arguing there.

In terms of topamax I admit I have never prescribed it and am not surprised I did not spell it correct! I do not argue it shows some weight loss but atleast in my view adding a medication with side-effects to combat the side-effects of another medication is more of a last-resort tactic. I feel it is prudent to change to a medication or dose of the same medication that has less side-effects that concern you and if you are unable to do that or if the patient needs the medication that produces side-effects than introducing something like topamax may be a last resort. However knocking off 10-12 pounds is unlikely to combat severe obesity and diabetes induced by an atypical.

I am more inclined to involved personal trainers, diet and excercise if they can afford it. If not atleast education about healthy living and getting them on the most benign medication in terms of side-effects.

Maybe others can chime in on using topamax as a first line approach rather than switching medications or lowering dosages if the patient has not had a trial on many more benign medications (not someone who has already failed other medicines and requires a side-effect heavy medicine for mental stability).

I agree benzo's will go when other titration is complete.

 

[billypilgrim37]

Risperdal is primarily a 2d6 substrate, and tegretol a 3A4 inducer. While the drugs are never actually that clean, the interaction between these two isn't among your biggest problems.

 

[Slingshot]

Here is just a quick literature objective study and in practice as you alluded to risperdal and tegretol both (along with many) due not tend to be clean in nature in terms of how they are effected and how they effect.

http://www.ncbi.nlm.nih.gov/pubmed/10942191

 

[vistaril]

Tegretol actually is FDA approved for acute manic/mixed episodes in bipolar disorder. I agree there is no indication for maintence and prevention of symptoms in bipolar disorder but if you take a look at a great couple pages from the APA psychopharm book they list every tegretol study available and really comes out as well as any other tested medicine for this indication. But not arguing there.

In terms of topamax I admit I have never prescribed it and am not surprised I did not spell it correct! I do not argue it shows some weight loss but atleast in my view adding a medication with side-effects to combat the side-effects of another medication is more of a last-resort tactic. I feel it is prudent to change to a medication or dose of the same medication that has less side-effects that concern you and if you are unable to do that or if the patient needs the medication that produces side-effects than introducing something like topamax may be a last resort. However knocking off 10-12 pounds is unlikely to combat severe obesity and diabetes induced by an atypical.

I am more inclined to involved personal trainers, diet and excercise if they can afford it. If not atleast education about healthy living and getting them on the most benign medication in terms of side-effects.

Maybe others can chime in on using topamax as a first line approach rather than switching medications or lowering dosages if the patient has not had a trial on many more benign medications (not someone who has already failed other medicines and requires a side-effect heavy medicine for mental stability).

I agree benzo's will go when other titration is complete.

1) I agree with everything you say about Tegetrol and it's fda indications and the studies we do have. But from a purely ebm standpoint(and all else being equal, which it isnt I suppose in this case), Depakote/Lithium(depending on the characteristics of the bipolar d/o) are considered the first line agents of choice....the reason being(I guess?) there is just more data supporting efficacy for maintenance in those two.
2) I don't think we have enough information about the clinical scenario to know that the benzo eventually needs to go. maybe it should and maybe it shouldn't, but just looking at a medication list and assuming a benzo shouldn't be there chronically in most cases isn't the right approach imo.

 

[IAmAUser]

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[splik]

tegretol xr is the licensed version for acute mania

 

[IAmAUser]

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[BobA]

The other thought I had was to simply lower the consta dose for 2 shots. Do one 37.5 mg shot, than a 25mg shot and then stop.

Any other thoughts?

It would depend how bad the previous manic episodes were. If they were extremely severe I would get her therapeutic on the Tegretol before reducing the risperdal, or taper the risperdal with the extra shots as above.

If the previous manic episodes were short and not that severe then I think just stopping the risperdal would be fine.

I have no evidence to back that up, but it seems reasonable.

 

[Slingshot]

I definetly learned something! i did not know it was only one form of tegretol approved so good to know. Of course we all know that is only because tegretol was simply generic by the time it struck the drug companies to try for approval for a psych indication so thus the extended release form. The variety of tegretol extended release has always confused me. XR, carbetrol etc etc.

I forgot to comment while I used to be ok with Trileptal, I have had terrible luck with multiple patients getting hyponatremic on inpatient units. Now as an outpatient doc I just do not think it is worth it, given it also has the least evidence. I would rather deal with tegretol drug interactions instead of that pesky hyponatremia!


Ultimately I decided to give one 37.5 and then one 25mg shot to get off the shot. Started titrating up until tegretol. Once tegretol is at steady state goal dose and she has had atleast 2 months after the final shot, and she is stable I will taper the oral by 1mg per month.

Like I said I have the luxury of having no rush and a patient who is quite stable.

Thanks for all the input!

 

[nitemagi]

I'd add a consideration of converting her to oral risperdal equivalent to the consta, titrating up after stopping the consta (2mg-->8mg/day) over a month. The goal I'd make is to keep close to a steady state risperdal, load the tegretol, then taper the risperdal over a longer period of time monitoring for breakthrough mania and for overmedication. Half-life for consta is in the 3-6 day range, so should be out of her system by 1 month.

So I'd think about something like:
Day 0: Last consta shot. Keep risperdal 2mg/day.
Day 7: Start tegretol.
Day 14: Don't give new consta shot. Cont. tegretol, increase risperdal to 4mg.
Day 21: Monitor progress, check Tegretol level. If ok may raise risperdal to 6mg.
Day 28: Keep risp at 6mg or raise to 8mg/day. Titrate up tegretol if needed.

The difficulty is I try not to change more than 1 variable at a time.
The general strategy I'd aim for would be to get tegretol to right level, match the risperdal to the consta dosing, taper down risperdal slowly, and see how it goes. Then might need to add in other med.

 

[billypilgrim37]

Half-life for consta is in the 3-6 day range, so should be out of her system by 1 month.

Consta doesn't even peak for a few weeks after first injection (and is hardly detectable in serum the first week or so after injection)... it doesn't get out of people's systems for a LONG time, especially after they've been on it for a while. I had plenty of people who would decide they didn't want to be on consta, tell me I didn't know what I was talking about (even though they were still coming to see me every week or so), and then get floridly psychotic after about two months when it was finally starting to get out of their system. That seemed to correlate with about the time, as I understood it, that their serum levels would actually be decreasing substantially.

I don't think it makes any sense pharmacokinetically to give people stepped down doses of Consta. It's sorta like if you were dropping down a really deep pit, but then a squirrel jumped on your back. You're going to hit the ground about the same time, but in one scenario you had a squirrel on your back, and the other you didn't.

 

[Slingshot]

The conversion to oral is an interesting thought. I guess in my eyes you are losing the benefit of the shot being such a nice prolonged natural slow "taper" given its kinetics and as mentioned, once at steady state after 4 shots of risperdal, it stays at close to steady state levels for almost a month and then slowsly dissipates. So once at steady state, it actually takes as long as it initially took to reach steady state to reach almost fully cleared. Which is 2-3 months. I always found the kinetics and thus dosing the injectables half science and half guess work. I do not plan using it much in an upper end practice but still need to know as I learned you never know who may be a patient!

Thanks for all the input