Manic pt with bad diabetes in DKA

[Messerschmitts]

Hey everyone, I'm on the psychiatry C/L service right now, and we have a female pt in her mid-50's who initially came into the psych ER classically manic but was found to be in DKA with very high blood glucose. She was started on seroquel, and now she is still on medicine with resolving DKA but is still manic and on seroquel 400mg po qhs. This is actually not my patient (being followed by a different resident on the team), but my attending today pimped me and asked what I would do. I initially said I'd probably bump her up to 600 or 800, but he said, "you really want to do that with a pt with bad diabetes and resolving DKA"? He expects me to come up with an answer by tomorrow.

What would you guys do? Switch her to risperidone? Add a mood stabiliser? Switch to a typical antipsychotic? Much thanks for some inisght.

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[BobA]

I would add a mood stabilizer. Tegretol has good data for both acute mania and maintenance treatment and has is relatively benign compared to Lithium and Depakote. Lamictal's another possibility, but I don't think it's nearly as well studied as Tegretol.

You would need to watch for drug drug interactions.

Seroquel I think would be fine during the acute phase of the illness. What she needs now is insulin, fluids, K+, etc. In the long term it'd be better to try a mood stabilizer as monotherapy, or consider Tegretol + Abilify.

 

[zenman]

What about Geodon?

 

[silas2642]

I would add a mood stabilizer. Tegretol has good data for both acute mania and maintenance treatment and has is relatively benign compared to Lithium and Depakote. Lamictal's another possibility, but I don't think it's nearly as well studied as Tegretol.

You would need to watch for drug drug interactions.

Seroquel I think would be fine during the acute phase of the illness. What she needs now is insulin, fluids, K+, etc. In the long term it'd be better to try a mood stabilizer as monotherapy, or consider Tegretol + Abilify.

If she is truly manic, why not add on lithium?

 

[billypilgrim37]

DKA is typically for type 1 diabetes. That's pretty irrelevant to seroquel.

 

[sunlioness]

I probably would have done Lithium plus maybe risperdal. Not that I'm overly worried about the Seroquel in this patient, just not overly impressed with it in general.

 

[whopper]

Problem with Seroquel is it can exacerbate metabolic problems and can be raised only to 100-200 mg per day. If she's manic 400 mg is on the low spectrum that'd work. You could, however, continue to raise it.

I'd try stuff that's potent where maximal dosages could be reached more quickly to stabilize her and the worry about transitioning to better long-term meds later.

Lamictal can take 6 weeks to get to a decent therapeutic range and the data suggests it doesn't get people out of mania well. It keeps them out of it, but once they're in it, it doesn't do much.

Without knowing specifics, it's hard to offer specific recommendations.

IMHO each psychotropic medication is better or worse given the situation. Lithium, while being highly effective for mania, can in the long run screw up kidneys and for that reason I tend to shy away from it in diabetics since their kidneys are already on the firing line. That doesn't mean don't ever use it on a diabetic, but you got to weigh all the options. What if lithium is the only thing that works on this patient?, what if she needs to be stabilized immediately due to comorbid medical problems, etc, these things would make me consider lithium. Good psychopharm recommendations require the doctor see the entire patient's history, the current situation, the long-term outlook, and having knowledge of the pros and cons of each specific med.

 

[BobA]

If she is truly manic, why not add on lithium?[/QUOTE}

As whopper noted, Lithium + DM could have increased chance of kidney disease.

Also, tegretol has a lot of data behind it.

 

[BobA]

What about Geodon?

I'd be worried about the QT prolongation in someone who is in acute DKA where there is a greater than usual chance of arrhythmia.

Once the DKA is resolved, I think geodon's a fine med with good side effect profile (even if slightly less effective).

 

[whopper]

In serious cases where there's serious problems and medical issues, my first goal is to stabilize, and once stabilized, I'd worry more about what meds would work better long-term.

E.g. if a guy is throwing chairs, I'm going to pull out the big guns first. When he's no longer an immediate danger then I'll try the stuff that hopefully will have less side effects.

But like I said, given that we don't know everything about this case (e.g. not being able to see the patient's EKG), I'm hesitant to give specific recommendations.

 

[Messerschmitts]

Thanks to everyone for their input. I believe her EKG is fine. Like I said, she's not a pt I'm personally following, so I don't know everything about her case, I'm mainly asked as an academic pimp question. I was thinking of suggesting lamotrigne but of course there is the problem of slow titration. I am thinking of still suggesting the uptitration of the seroquel in the acute period, I think that's not the answer my attending wants but I honestly think it's what I would do if I was the attending, and then switch to a mood stabiliser (perhaps carbemazapine as the board suggests) later, then add Abifliy/Geodon if needed.

 

[kugel]

I'm not impressed with antipsychotics as mood stabilizers. Haldol has been used as an adjunct in acute mania for decades, but few thought it was a serious mood stabilizer. Since every SGA puts out millions to get FDA approval, a lot of people have started referring to them as mood stabilizers, but I don't buy it. I think they do help reduce psychosis associated with acute mania, but that's not the same thing. If I'm looking to add an antipsychotic to mood stabilizers in a pt with diabetes (not something I relish), I would be likely to consider an FGA first for metabolic reasons. Is there an SGA that hasn't been known to induce DKA or at least raise glucose levels? Why go there?

As for the mood stabilizer, Depakote, Tegretol, Lithium are your best choices, esp in acute mania. I agree with other posters that Tegretol has been ignored too often in the last 10-20 years. I believe anyone with Bipolar 1 deserves a good full trial on Lithium, unless it is absolutely contraindicated. Every couple years, another important review re-states that Lithium is still the Gold Standard. Renal complications are a potential concern. Some believe Depakote pulls people out of mania faster. I don't know about that. With Depakote or Tegretol, consider loading doses to reach steady state ASAP.

Don't forget about judicious use of BZD's as an adjunct in acute mania, even at fairly high doses. Getting/keeping these patients calm (and getting them some sleep) can save lives. Use appropriate doses and raise them according to a schedule you set. Chasing the mania with ever increasing doses can be dangerous. Once they catch up with the patient, he crashes so bad that he's unresponsive and goes to the ICU. In these patients, it takes 50-100% longer for the doses to work. If you use a schedule dose with PRN's, use tiny PRN's. e.g., if you Rx "Ativan 2 mg PO q 4 hrs unless drowsy/asleep," he WILL begin to calm and eventually sleep, but it will likely take 2-3 doses. If you want to add a PRN, use 0.5 mg-1 mg, so that by the time he goes down, he won't have had so much that you have to put him on continuous Pulse Ox to be sure he's still breathing.

I had a pt so manic he could not avoid contantly wandering into others' rooms and had not slept in days. I finally ordered Ativan 1mg PO q 30min and I sat up watching him (beginning at 2am), until he finally could sleep a full hour. Then I set him a scheduled dose and I went to sleep.

 

[zenman]

Thanks to everyone for their input. I believe her EKG is fine. Like I said, she's not a pt I'm personally following, so I don't know everything about her case, I'm mainly asked as an academic pimp question. I was thinking of suggesting lamotrigne but of course there is the problem of slow titration. I am thinking of still suggesting the uptitration of the seroquel in the acute period, I think that's not the answer my attending wants but I honestly think it's what I would do if I was the attending, and then switch to a mood stabiliser (perhaps carbemazapine as the board suggests) later, then add Abifliy/Geodon if needed.

As an aside how fast do you titrate Lamictal on inpatients? My attending bumps it up every 3 days.

 

[whopper]

Lamictal 25 mg Qdaily x 2 weeks
then
Lamictal 50 mg Qdaily x 2 weeks
then
Lamictal 100 mg Qdaily x 1 week
then
Lamictal 150 mg Q daily x 1 week
then Lamictal 200 mg Qdaily.

Again 6 weeks to reach the recommended dosage for bipolar disorder though for antidepressant augmentation it could work lower dosages.

From personal experience, if Lamictal's going to work for bipolar disorder and the patient is having symptoms, I tend to see some benefit at 100-150 mg a day. 200 is the recommended dosage but I've seen plenty of patients do better at higher dosages.

These are the manufacturer's guidelines. I haven't seen any data recommending it can be be titrated faster than this and I've seen doctors do that out of ignorance. Doing it faster raises the risk of Stevens Johnson Syndrome.

If there is data showing it can be raised faster let me know cause I haven't seen any.

 

[zenman]

That's the schedule I was using in outpatient, as well as inpatient, till she told me different. She's away this week but I'll ask when she returns.

 

[billypilgrim37]

That's the schedule I was using in outpatient, as well as inpatient, till she told me different. She's away this week but I'll ask when she returns.

I have had attendings who bump up every 3 days. Inpatient it's probably not unreasonable as patients are being monitored so closely (and the risk of SJ is still low, even if it it's very real).

That said, I do (and will continue to do) the same as Whopper. In fact, I've never seen those guidelines for the upper doses above 100, so I've generally even been a little more conservative than that getting them to 200.

 

[BobA]

I have had attendings who bump up every 3 days. Inpatient it's probably not unreasonable as patients are being monitored so closely (and the risk of SJ is still low, even if it it's very real).

That said, I do (and will continue to do) the same as Whopper. In fact, I've never seen those guidelines for the upper doses above 100, so I've generally even been a little more conservative than that getting them to 200.

I do 25mg per week until 100mg and then go from 100 to 150 to 200mg.

Neurologists, I believe, use a much quicker titration when using Lamictal for seizures. (They also use much higher doses).

 

[Doctor Bagel]

Lamotrigine would be 100% the wrong answer where I train. My understanding is that its evidence for acute mania is pretty much non-existent. It's a frequent source of lecturing here on why expert opinions sometimes don't match the data.

I agree with adding a mood stabilizer, but for acute mania, you're not going to see much of anything quickly. I also don't like quetiapine (and of course olanzapine) because of the metabolic side effects. Even if she's type I, being fat isn't going to be good for her regardless, and quetiapine makes lots of people fat (and maybe doesn't work that great at least from what I've seen). 400 mg is pretty low, though, so you could go higher. So yeah, lithium and ziprasidone make sense if her kidneys are good, and she doesn't have QTc issues. Benzos are also pretty OK in acute mania. For the antipsychotic piece, you could also think about a first generation antipsychotic. Perphenazine is our candy here, and I've used it in manic patients before -- it works about as well as anything else from what I've seen. If I recall, I think the recommendations for acute mania generally focus on 2nd generations, but I'm not sure of a reason why a first generation wouldn't work as well. And from the CATIE trial, perphenazine really didn't do worse the 2nd generations in terms of EPS.

 

[Doctor Bagel]

I'm not impressed with antipsychotics as mood stabilizers. Haldol has been used as an adjunct in acute mania for decades, but few thought it was a serious mood stabilizer. Since every SGA puts out millions to get FDA approval, a lot of people have started referring to them as mood stabilizers, but I don't buy it. I think they do help reduce psychosis associated with acute mania, but that's not the same thing. If I'm looking to add an antipsychotic to mood stabilizers in a pt with diabetes (not something I relish), I would be likely to consider an FGA first for metabolic reasons. Is there an SGA that hasn't been known to induce DKA or at least raise glucose levels? Why go there?

As for the mood stabilizer, Depakote, Tegretol, Lithium are your best choices, esp in acute mania. I agree with other posters that Tegretol has been ignored too often in the last 10-20 years. I believe anyone with Bipolar 1 deserves a good full trial on Lithium, unless it is absolutely contraindicated. Every couple years, another important review re-states that Lithium is still the Gold Standard. Renal complications are a potential concern. Some believe Depakote pulls people out of mania faster. I don't know about that. With Depakote or Tegretol, consider loading doses to reach steady state ASAP.

Don't forget about judicious use of BZD's as an adjunct in acute mania, even at fairly high doses. Getting/keeping these patients calm (and getting them some sleep) can save lives. Use appropriate doses and raise them according to a schedule you set. Chasing the mania with ever increasing doses can be dangerous. Once they catch up with the patient, he crashes so bad that he's unresponsive and goes to the ICU. In these patients, it takes 50-100% longer for the doses to work. If you use a schedule dose with PRN's, use tiny PRN's. e.g., if you Rx "Ativan 2 mg PO q 4 hrs unless drowsy/asleep," he WILL begin to calm and eventually sleep, but it will likely take 2-3 doses. If you want to add a PRN, use 0.5 mg-1 mg, so that by the time he goes down, he won't have had so much that you have to put him on continuous Pulse Ox to be sure he's still breathing.

I had a pt so manic he could not avoid contantly wandering into others' rooms and had not slept in days. I finally ordered Ativan 1mg PO q 30min and I sat up watching him (beginning at 2am), until he finally could sleep a full hour. Then I set him a scheduled dose and I went to sleep.

Maybe I should go back and delete my post because I agree about 100% with what you're saying.

 

[Telamir]

Hello. I'm an MS4 (just finished MS3!) and I was wondering why you guys were insisting on giving meds to this particular patient right now (as in when he's still in DKA) instead of waiting for the DKA to resolve? I would've thought it would be more prudent to wait for the DKA to resolve since some of the medication could interfere with his treatment or make it worse. Is know mania is a psychiatric emergency, but I wasn't aware its treatment preceded (or was just as important) as DKA.

I'm genuinely curious.

 

[zenman]

Hello. I'm an MS4 (just finished MS3!) and I was wondering why you guys were insisting on giving meds to this particular patient right now (as in when he's still in DKA) instead of waiting for the DKA to resolve? I would've thought it would be more prudent to wait for the DKA to resolve since some of the medication could interfere with his treatment or make it worse. Is know mania is a psychiatric emergency, but I wasn't aware its treatment preceded (or was just as important) as DKA.

I'm genuinely curious.

I would think the goal would be to work on both at the same time.

 

[Slingshot]

Sounds like a perfect patient to try a IV loading of depakene! Anyone else remember reading those few sources ( I think the APA psychopharm book alludes to anecdotal evidence for the rapid control of mania with iv depakene).

Suggest that and cite a source (apa psychopharm book) and look like an all-star. Than be shot down since nobody seems to ever do this in practice but I honestly always wanted to try this!

 

[freaker]

Typically the goal with a manic patient is to get them to sleep. Plenty works towards this end, though in my experience, nothing quite so well as thorazine with a little Ativan to push things along.

The patient isn't by chance delirious, is she? In DKA, I'd imagine that's a very real possibility.

 

[BobA]

Lamotrigine would be 100% the wrong answer where I train. My understanding is that its evidence for acute mania is pretty much non-existent. It's a frequent source of lecturing here on why expert opinions sometimes don't match the data.

I agree with adding a mood stabilizer, but for acute mania, you're not going to see much of anything quickly. I also don't like quetiapine (and of course olanzapine) because of the metabolic side effects. Even if she's type I, being fat isn't going to be good for her regardless, and quetiapine makes lots of people fat (and maybe doesn't work that great at least from what I've seen). 400 mg is pretty low, though, so you could go higher. So yeah, lithium and ziprasidone make sense if her kidneys are good, and she doesn't have QTc issues. Benzos are also pretty OK in acute mania. For the antipsychotic piece, you could also think about a first generation antipsychotic. Perphenazine is our candy here, and I've used it in manic patients before -- it works about as well as anything else from what I've seen. If I recall, I think the recommendations for acute mania generally focus on 2nd generations, but I'm not sure of a reason why a first generation wouldn't work as well. And from the CATIE trial, perphenazine really didn't do worse the 2nd generations in terms of EPS.

I don't think anyone was suggesting lamictal should be used for acute mania - it takes over a month to get to a therapeutic level! I took it as a side question.

If you look at the Cochrane reviews, the two most effective meds at Olanzapine and Haldol (although admittedly AP's on a whole are close to equal). I prefer Olanzapine acutely to haldol because there's very little risk of acute dystonia. I view using Olanzapine as a acute treatment med only, while getting therapeutic on a mood stabilizer (Lithium/Depakote/Tegretol) and then attempt monotherapy usually with Lithium. The Olanzapine is usually slowly reduced on an outpatient basis over a few months. I like benzo's in mania too.

 

[NJWxMan]

I think Olanzapine would be a very poor choice in this patient. While rotating several months on the geri-psych unit, I ordered PRN Olanzapine on patients with agitation+DM (on insulin) only to find out that 20 mins later that their fingerstick was 350. I think Trileptal or Depakote would be most fitting as a long term agent. DKA patients are normally quite fatigued and I highly doubt that agitation would be a big issue. I would avoid antipsychotics until her DKA resolves.

I don't think anyone was suggesting lamictal should be used for acute mania - it takes over a month to get to a therapeutic level! I took it as a side question.

If you look at the Cochrane reviews, the two most effective meds at Olanzapine and Haldol (although admittedly AP's on a whole are close to equal). I prefer Olanzapine acutely to haldol because there's very little risk of acute dystonia. I view using Olanzapine as a acute treatment med only, while getting therapeutic on a mood stabilizer (Lithium/Depakote/Tegretol) and then attempt monotherapy usually with Lithium. The Olanzapine is usually slowly reduced on an outpatient basis over a few months. I like benzo's in mania too.

 

[BobA]

I think Olanzapine would be a very poor choice in this patient. While rotating several months on the geri-psych unit, I ordered PRN Olanzapine on patients with agitation+DM (on insulin) only to find out that 20 mins later that their fingerstick was 350. I think Trileptal or Depakote would be most fitting as a long term agent. DKA patients are normally quite fatigued and I highly doubt that agitation would be a big issue. I would avoid antipsychotics until her DKA resolves.

Are you implying that the Olanzapine acutely increased the blood sugar?

 

[NJWxMan]

Yes, I am. There are case reports to suggest that Olanzapine can cause a rapidly occurring hyperglycemia in patients without DM. I can only imagine what it can do in elderly patients with DM.

 

[nitemagi]

Yes, I am. There are case reports to suggest that Olanzapine can cause a rapidly occurring hyperglycemia in patients without DM. I can only imagine what it can do in elderly patients with DM.

There's also good data that olanzapine can cause insulin resistance PRIOR to weight gain and appetite issues.

 

[Slingshot]

There's also good data that olanzapine can cause insulin resistance PRIOR to weight gain and appetite issues.

Are you talking acutely after a a dose or two? I have always wondered whether there is any acute effect on blood sugar/insulin resistance with either an overdose or a relatively high dose in someone potentially naive or less accustomed to taking it? For any atypical for that matter.

 

[BobA]

I'm sure that can happen, but I don't know it's a good idea to base practice on case reports. For what it's worth typicals can also lead to insulin resistance (although less commonly), as well as acute dystonia, longer QTc prolongation, increased risk of death in the elderly . . .I don't think there's a perfect answer.

 

[Slingshot]

I'm sure that can happen, but I don't know it's a good idea to base practice on case reports. For what it's worth typicals can also lead to insulin resistance (although less commonly), as well as acute dystonia, longer QTc prolongation, increased risk of death in the elderly . . .I don't think there's a perfect answer.

To be fair a blanket statement that typicals increase qtc and cause increased risk of death in the elderly is not really accurate since both atypicals and typicals have the same black box warning for death in elderly.

Haldol has one of the lowest qtc changes, especially orally when compared to even the atypicals.

Dystonia and akathesia yes typicals tend to be worse.

 

[BobA]

I think Olanzapine would be a very poor choice in this patient. While rotating several months on the geri-psych unit, I ordered PRN Olanzapine on patients with agitation+DM (on insulin) only to find out that 20 mins later that their fingerstick was 350. I think Trileptal or Depakote would be most fitting as a long term agent. DKA patients are normally quite fatigued and I highly doubt that agitation would be a big issue. I would avoid antipsychotics until her DKA resolves.

BTW - I wasn't suggesting Olanzapine for this particular patient. If you look back, I suggested a mood stabilizer such as Tegretol.

I was just saying that in general Olanzapine is one of the more effective treatments for mania.

 

[vistaril]

Hey everyone, I'm on the psychiatry C/L service right now, and we have a female pt in her mid-50's who initially came into the psych ER classically manic but was found to be in DKA with very high blood glucose. She was started on seroquel, and now she is still on medicine with resolving DKA but is still manic and on seroquel 400mg po qhs. This is actually not my patient (being followed by a different resident on the team), but my attending today pimped me and asked what I would do. I initially said I'd probably bump her up to 600 or 800, but he said, "you really want to do that with a pt with bad diabetes and resolving DKA"? He expects me to come up with an answer by tomorrow.

What would you guys do? Switch her to risperidone? Add a mood stabiliser? Switch to a typical antipsychotic? Much thanks for some inisght.

If she's still classically manic I'd probably use Haldol, Risperdal, or Olanzapine acutely to control this on the medical floor......probably Haldol or Olanzapine because it comes IM. Longterm recs I would consider Depakote if she has a clear hx of mania. If weight gain happens certainly a switch to Tegretol is a consideration.

A key point(and this why I am confused by your attending's question) is that the side effect profile for Seroquel does not increase linearly with dose increases. For example, someone on 100mg of seroquel does not have only 12.5% of the metabolic side effects of 800mg....that's why I am sorta puzzled over your attendings question as I assume he is thinking that is what the pt is going to be treated on longterm since who the heck really cares how she is treated acutely.......Seroquel is reasonable I suppose. For acute mania on a consult service I just prefer to put in antipsychotic recs that come IM as well because manic pts may refuse and that just then becomes a hassle for the medicine service if they get out of control.

 

[whopper]

Yes, I am. There are case reports to suggest that Olanzapine can cause a rapidly occurring hyperglycemia in patients without DM. I can only imagine what it can do in elderly patients with DM.

Repeating what was said above, but giving a more specific example, I've seen data that Olanzapine affects the GLUT receptors in the intestine and for most of us psychiatrists (and for that matter pretty much all MDs) who forgot what those are, they regulate carb absorption in the GI tract.

http://www.ncbi.nlm.nih.gov/pubmed/16002093

This also somewhat backs the theory that Zydis and Relprevv are not quite as bad as regular oral Zyprexa for metabolic side effects because the two meds bypass the GI tract.

As I wrote above, it's hard to determine just what is the best med for a situation like this. Geodon and Abilify, while more metabolically neutral are less efficacious vs. the other antipsychotics. The more efficacious ones tend to cause more metabolic effects. Sometimes the best med really comes down the the delivery method. If the patient is swinging, you usually have to inject them and that limits the choices to what's injectable. By the way, I read a recent article showing that one of the typicals may soon come in an inhalable form.

http://www.healio.com/Psychiatry/jo...Loxapine-for-the-Treatment-of-Acute-Agitation

A problem with carbamazepine is that if the patient is on multiple meds, it could screw with the metabolism of several of them, in addition to being able to only give limited dosages that may not be efficacious at first and can only be raised to higher levels after the patient's been on the medication for a few days at the least.

Without more data, it's hard to peg down a best medication.

I've often-times complained that I find so many doctor's med choices idiotic. E.g. a psychiatrist who puts someone with chronic kidney disease on lithium, and yes I've seen that, but even the best docs will only be able to argue within a range of what meds are better vs. worse. If I saw a psychotic patient in good health, first break, with no specific factors making this patient out of the ordinary, there's not much ground in arguing that Geodon vs. Abilify vs. Risperdal is going to be significantly superior until you give one a try and see what happens.

 

[Slingshot]

A problem with carbamazepine is that if the patient is on multiple meds, it could screw with the metabolism of several of them, in addition to being able to only give limited dosages that may not be efficacious at first and can only be raised to higher levels after the patient's been on the medication for a few days at the least.

.

Actually in an acute situation, this would be irrelevent. Enzyme induction takes days and days to weeks to become signifigant. Look at auto metabolism of tegretol. Begins to lower levels of itself at about 2 week range which is why you check levels every 2-3 weeks after you hit a target dose to see how it is effected.

Therefore unless if used short-term for a couple weeks it would be inconsequential. I agree if they were on a regimn with tons of medications which would be effected long-term than it would not be worth it but this could easily be thought of before.