using Olanzapine in liver disease

[ghost dog]

Hey peeps,

I wanted to put this question to you, as I currently have an uncontrolled bipolar pt ( I think) in my practice who refuses to see a psychiatrist for an expert opinion.

This person has very little insight into their condition, and although she has pretty much all the symptoms of mania, denies them. I previously suggested a trial of Olanzapine, she refused, stating that this medication was "for crazy people". I believe that I have now convinced her that this med may be for her, as the side effect profile includes sedation and weight gain ( she complains of insomnia and emaciation).

My question here is that she has Hepatitis C, and liver enzymes 2 - 3 times the ULN. Is Zyprexa contra-indicated here, or can I start on a baby dose of 2.5 mg OD and follow her bloods closely ?

To complicate matters further, I am tapering her off the Fentanyl patch ( she is currently on 75 mcg Q 3days ).

I suppose I could always get a GI opinion, but this would take quite awhile in my neck of the woods.

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[splik]

There are two issues here - the first is regarding the pharmacokinetics in liver disease, the second is regarding the effects of olanzapine on the liver.

Raised LFTs alone are not really a good indicator of the extent of the liver disease, especially if the levels are consistently raised at the same level bearing in mind there is a significant amount of redundancy to the liver. Thus the raised LFTs are not that much of an issue. I would be more concerned if pt was jaundiced, had low albumin, or raised PT/INR. Thus raised LFTs (if asymptomatic and not accompanied by derangements in synthetic liver function) are not a contraindication to olanzapine therapy.

All antipsychotics can cause raised LFTs or more rarely hepatotoxicity. This is more of an academic issue but is something to bear in mind with someone who may have chronic liver disease. For some reason I seem to recall there may be a stronger association of hepatotoxicity with olanzapine than risperidone or quetiapine but don't quote me on that. Nevertheless I would be more inclined to use risperidone if there was a possibility of liver decompensation as you are less likely to completely zonk the patient out in that instance.

Lithium is pretty much the only drug for bipolar which is not potentially hepatotoxic and whose pharmacokinetics are not affected by chronic liver disease.

 

[Divine Furor]

Just some thoughts--

1) If she's truly manic in a DSM-IV bipolar style, verging on hospitalizable (like that? new adjective), I don't know that 2.5mg of Zyprexa is going to bring you much joy. Low-dose starters of antipsychotics are very fashionable right now with the current thinking about dopamine receptor states, but treatment of psychosis that way takes a LONG time and requires a diligent patient with good compliance.
2) Since the thio-derivative antipsychotics are known to increase liver enzymes, you might be putting her at risk for questionable benefit. Maybe her liver disease would increase the serum levels of olanzapine, but that's not something you could take to the bank.
3) Lithium would, of course, be a great choice if she's maintained her renal fxn....and it also causes sedation and weight gain, but it needs monitoring and it screams, "PSYCH."

 

[whopper]

I've had several patients with Hep C and were on Zyprexa. The problem I've mainly faced with Zyprexa was not the stress on the liver but the metabolic problems and it's effects on ANC.

If you want to be cautious, you could order LFTs with the same frequency you'd order a lipid profile.

But even if it did cause harm to the liver, you have to weigh everything altogether (or more like the patient needs to and make a decision). Taking a med that puts some stress on the liver or lithium (which is not exactly the most benign med even if you have healthy kidneys), or no med at all, and if you have bipolar disorder you are most definitely in need of a medication.

 

[BobA]

Also, hepatic encephalopathy CAN present like mania. It's not always hypoactive.

How old is this person? What's their ammonia level?

If it were truly a bipolar illness you would expect a longer history of psych involvement whether through hospitalization or outpatient care, etc.

 

[freaker]

Nevertheless I would be more inclined to use risperidone if there was a possibility of liver decompensation as you are less likely to completely zonk the patient out in that instance.

Lithium is pretty much the only drug for bipolar which is not potentially hepatotoxic and whose pharmacokinetics are not affected by chronic liver disease.

Why not Invega if you're going to use risperidone (other than the obvious cost issue)? About 70% of it bypasses the hepatic metabolism. Others may weigh in differently, but I rarely use it outside of patients with liver disease.

 

[splik]

Why not Invega if you're going to use risperidone (other than the obvious cost issue)? About 70% of it bypasses the hepatic metabolism. Others may weigh in differently, but I rarely use it outside of patients with liver disease.

I have never rx Invega mainly for cost reasons but also it just sounded like a con! (I never rx lexapro either). I would use risperidone over olanzapine for pharmacodynamic reasons (less sedating) than pharmacokinetic reasons so there would be no added benefit from that point. If you were concerned about EPSE which of course is the major drawback of risperidone over olanzapine or even QTc prolongation then I agree that pharmacokinetics would be more of a consideration and invega would theoretically be a better choice.

 

[nitemagi]

I have never rx Invega mainly for cost reasons but also it just sounded like a con! (I never rx lexapro either). I would use risperidone over olanzapine for pharmacodynamic reasons (less sedating) than pharmacokinetic reasons so there would be no added benefit from that point. If you were concerned about EPSE which of course is the major drawback of risperidone over olanzapine or even QTc prolongation then I agree that pharmacokinetics would be more of a consideration and invega would theoretically be a better choice.

Sometimes it's just pt. preference. I have had young schizophrenics who I've started on invega (because they're acutely psychotic and we have samples on hand), who really really didn't like risperdal when I tried switching them. Sometimes you go with what they'll take, because it's better than them being uncontrolled.

The only other benefit is sustenna.

I think the OP has posted far too little information for us to give any useful recommendations. We don't even know the age range. People are shooting in the dark about delirium as an explanation for a bipolar d/o, which we have no evidence to support aside from elevated LFT's.

 

[whopper]

The price of Invega needs to be an issue. If we doctors started prescribing meds with cost as a factor, collectively we could save billions.

But I have seen some patients that reacted better on Invega vs. Risperdal when tried on both. The number was extremely small. The first few times I did it, it was because the patients were on depot meds and they were highly resistant to medication treatment. (E.g. they had to be held down when injected). Doing that once a month instead of twice was safer for the patient and staff members.

One may argue that there's no exact conversion between the two meds so how do I know? I know because the improvement/side effect ratio differed. E.g. on Risperdal, one of my patients had EPS and her psychosis was worse, on Invega, no EPS and psychosis is less. But I reiterate that I only this on a few patients, and only did so if they did have some benefit on Risperdal and there was a specific reason to try Invega instead such as the above of if they were having significant side effects to Risperdal.

 

[ghost dog]

Also, hepatic encephalopathy CAN present like mania. It's not always hypoactive.

How old is this person? What's their ammonia level?

If it were truly a bipolar illness you would expect a longer history of psych involvement whether through hospitalization or outpatient care, etc.

She is around 50. Indeed, she has received a court ordered psych assessment in the past due to alcohol related issues (and thus the refusal to be assessed by psych again). She is a serious PIA.

At her next visit, I'm going to arrange some comprehensive bloodwork to get a better look at her liver, which will include a BAL.

As another poster indicated, I will slowly titrate the Olanzapine ( starting at a very small dose) if synthetic liver function is normal. Every time I see her, she is talking a mile a minute, hyper irritable, dresses flamboyantly, is inappropriate in the clinic (i.e. yelling and / or hugging staff members ) and catastrophizing about her pain symptoms (fibromyalgia).

Her urine drug screens have always been negative for drugs of abuse. However, she did " water " her last screen; I believe this was more due to a lack of insight rather than trying to
avoid detection of a illicit substance. When I confronted her about this, she stated that she couldn't urinate, and thus put water into the container (as " I would be mad " if she couldn't give me a sample). Regardless, I visualized the fentanyl patch on her person, and she is being tapered off ( in short order ! ).

She also alludes to non-specific chronic paranoid delusions, in regards to a number of people out to get her ( this has been going on for a number of years ). She seems to be getting along " OK " in the community, in that she is not an immediate threat to herself or others. She is rail thin, however.

I believe she scores about 41 points on the Young Mania Rating Scale.

I am veerrry close to discharging her.

 

[masterofmonkeys]

I would wonder about a personality disorder as well such as Histrionic or Borderline PD. Hard to diagnose over the internets, but if these appear to be relatively stable traits of personality instability (lol) could explain a lot of her symptoms.

 

[ghost dog]

I would wonder about a personality disorder as well such as Histrionic or Borderline PD. Hard to diagnose over the internets, but if these appear to be relatively stable traits of personality instability (lol) could explain a lot of her symptoms.

This is true; I spoke to her previous family physician and this was mentioned.

I am certainly not an expert in these matters; however, it is really a problem as this patient refuses expert consultation and she really causes problems in the office whenever she comes in.

One instance of strange and inappropriate behavior sticks out in my mind: I hear uncontrolled laughter come out of one of my exam rooms. At first I thought it was this patient; it turned out to be my nurse, as the patient was rapping ( literally ) for her. The RN was so surprised by this, she burst out into laughter.

The patient is a 50 yr old italian woman.

I really doubt that this is purely an Axis II disorder. Of course, I have been wrong before.

 

[masterofmonkeys]

This is true; I spoke to her previous family physician and this was mentioned.

I am certainly not an expert in these matters; however, it is really a problem as this patient refuses expert consultation and she really causes problems in the office whenever she comes in.

One instance of strange and inappropriate behavior sticks out in my mind: I hear uncontrolled laughter come out of one of my exam rooms. At first I thought it was this patient; it turned out to be my nurse, as the patient was rapping ( literally ) for her. The RN was so surprised by this, she burst out into laughter.

The patient is a 50 yr old italian woman.

I really doubt that this is purely an Axis II disorder. Of course, I have been wrong before.

While meds are not considered 'treatment' for personality disorders, they have plenty of evidence for at least SOME benefit in these populations anyway. And it's rare to meet someone with an Axis II who doesn't have some sort of Axis I or at least a history of it. Plenty of evidence to suggest true bipolar is more prevalent in Cluster B patients as well.

So I certainly wouldn't be afraid of using meds and they'd probably benefit more than nothing would. Seroquel, while liver-metabolized, may also be an option. Also generic if that is an issue.

Brief look at prescribing information also indicated that olanzapine metabolism isn't significantly affected by cirrhosis.