When to start Clozaril

[kugel]

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Under what circumstances do each of you start Clozaril?
How many antipsychotics must fail first?
How do you define "failure?"
How many hospitalizations in what period of time?
Do you think we, as a group, wait too long before trying Clozaril?
Do you use it for treatment resistant Bipolar? When?

 

[Hurricane]

In my limited experience (pgy3 resident), I have only started clozaril during inpatient admissions, usually in patients that prior to me seeing them had failed multiple meds and been hospitalized multiple times. (The one exception to this was a first break catatonic patient that we started cloz on after she failed two atypicals and it was like turning on a light switch, amazing)

As to the question of whether we wait too long - I dunno but we certainly wait longer than the APA guidelines recommend, which is after failure of two meds including at least one atypical. Or persistent suicidal ideation/behavior.

 

[whopper]

Per guidelines 2 antipsychotics must have failed.

Personally I will not give up after 2 antipsychotics. Clozaril though effective has a lot of side effects & requires multiple dosings during the day. While the product label does not require it, when you reach the higher doses, you dramatically increase the risk of seizure. For that reason several doctors will add an anti-seizure med which only increases the side effect risks.

Before I consider Clozaril, I will try at least Zyprexa or Risperdal at high doses mixed with a typical antipsychotic. I'm talking Zyprexa 40mg a day. I wouldn't give up on other antipsychotics unless you've tried one of these 2 mixed with an antypical. I certianly wouldn't start Clozaril if only the less efficacious atypicals such as Seroquel or Abilify were tried.

One benefit with working on a forensic unit is you get the sickest of the sickest. We're talking people who murder people when psychotic. I've never gotten the exposure or experience with using Clozaril that I now have working on this unit.

 

[Faebinder]

Per guidelines 2 antipsychotics must have failed.

Personally I will not give up after 2 antipsychotics. Clozaril though effective has a lot of side effects & requires multiple dosings during the day. While the product label does not require it, when you reach the higher doses, you dramatically increase the risk of seizure. For that reason several doctors will add an anti-seizure med which only increases the side effect risks.

Before I consider Clozaril, I will try at least Zyprexa or Risperdal at high doses mixed with a typical antipsychotic. I'm talking Zyprexa 40mg a day. I wouldn't give up on other antipsychotics unless you've tried one of these 2 mixed with an antypical. I certianly wouldn't start Clozaril if only the less efficacious atypicals such as Seroquel or Abilify were tried.

One benefit with working on a forensic unit is you get the sickest of the sickest. We're talking people who murder people when psychotic. I've never gotten the exposure or experience with using Clozaril that I now have working on this unit.

Ya, I think I'd give Geodon or Invega a try after Risperdal and Zyprexa fail together..

Unfortunately, the 4.X day limit on inpatient hospitalizations makes this impossible.

 

[whopper]

On the unit you're on I wouldn't try Clozaril unless the patient was already on it.

One thing I've learned while working the forensic unit is before you start Clozaril, if your patient was previously on it, you need to contact all the clozaril registries. Under specific guidelines, you can't restart clozaril if the patient's WBC &/or neutrophil levels went below a certain level. Often times the patient is an unreliable historical source.

Clozaril registries have the lab data of the patient's use of clozaril. However since several companies now produce clozaril, you'll have to contact all of them.

 

[strangeglove]

Why are the relatively rare scary side effects of Clozaril thought of as less problematic than the almost certain side effects of combining 2 or more typical antipsychotics, especially when there is excellent evidence of Clozaril working well and no evidence (i.e. negative evidence) for combining antipsychotics.

 

[whopper]

Clozaril's side effects seen as less problematic? Its really depends on who you ask. Some docs I've seen are more or less gung ho about using it. Some never use it except as a last resort. Others are more willing to use it earlier.

CATIE's data backed the notion that Clozaril had higher efficacy than the other atypicals. It IMHO opened more doctors to using it because its data showed patients were more likely to stay compliant on it than the other atypicals, possibly because the efficacy is so much higher, they're willing to live with the side effects.

I don't know if I'd consider mixing 2 typicals. Of course I guess if nothing else works, you can start trying that, but there's several typical & atypical & atypical combinations that can be attempted.

One stumper I've encountered is what the heck do you do if you've maxed out the patient on the highest dose of Clozaril & they still are psychotic? I did a lit review & there was no good data showing that anything worked well mixed with Clozaril except for amisulparide which unfortunately is not available in the US.

Another thing I didn't mention is I had never encountered a situation where an outpatient was started on Clozaril. I figure if their (edit, I incorrectly wrote "they're") psychosis is that bad, it would've started in inpatient & if anything would've continued after discharge.

 

[BabyPsychDoc]

Another thing I didn't mention is I had never encountered a situation where an outpatient was started on Clozaril. I figure if they're psychosis is that bad, it would've started in inpatient & if anything would've continued after discharge.

I started an outpatient on clozapine. A 70+ yo woman, chronic schizophrenia, tried all antipsychotics under the sun, was either unresponsive or non-compliant to those. She was "quietly" psychotic, shall I say...Did not threaten anybody, but was really afraid to go upstairs since she saw people and heard threatening voices each time she would go there. Downstairs it was, for some reason, better. She slept in her living room and had not been to her bedroom or bathroom for several years.

We are supposed to start clozapine on inpatients, but she firmly refused a voluntary admission and was not bad enough (under the UK law, at least) to be committed. The poor soul had a really bad experience with one and only admission that she had had - so I totally sympathised with her.

Anyway, I got our crisis team involved and community psych nurses. We organised her home care according to clozapine protocol for inpatients (ie, stay with the pt for the first 6 hrs, check BP, do the bloods at home, daily visits with supervision, etc). Logistics of the endeavour were quite complicated (once I had to do the home visit just to take her bloods, since a CPN called in sick that day), but it all worked out.

Retrospectively, it was probably a bit of a leap for a junior resident - and these days, I would have thought twice about doing something like this. But, the lady really improved (two months later she went to sleep in her bedroom) and nothing bad happened - so, I guess, "noli nocere..."

 

[whopper]

Well older patients, their (+) sx tend to burn out over time, & its usually the (+) sx that force an involuntary admission.

 

[strangeglove]

Why are the relatively rare scary side effects of Clozaril thought of as less problematic than the almost certain side effects of combining 2 or more typical antipsychotics, especially when there is excellent evidence of Clozaril working well and no evidence (i.e. negative evidence) for combining antipsychotics.

Sorry, I meant "more problematic."

 

[whopper]

Clozaril's effects can be fatal. Several of its side effects can also be permanent.

The big things to worry about with typicals are NMS (so rare its to the point where its almost never even considered until its encountered), EPS & metabolic effects. EPS side effects can be prevented & reduced with antihistamines & benztropine. Permanent EPS such as TD can be prevented by detecting characteristic mouth movements before TD actually starts & then lowering or stopping the typical.

Compare to Clozaril-fatality & permanent myelosuppression are big things to worry about. On top of that weekly blood draws are a pain in the butt, especially for a very psychotic patient who often times does not want to volunteer for them anyway. Its an irony-the sicker the patient, the more you want them on Clozaril, but the sicker the patient, the less likely they are to be compliant, complain about the side effects & not do the maintenance.

CATIE however showed that of the patients on Clozaril, more seem to stay compliant on it than was previously thought.

 

[OldPsychDoc]

Speaking of compliance--any of you encounter a manufacturer's discontinuation of Prolixin-D? I have a very stable 60 y/o schizophrenic who swears by his shots--out of the hospital for 12 years. We tried Consta 2 years ago, but he reported sexual s/e he wasn't having on the Prolixin (hey, psychotic pts need love too! 😉), and requested to go back. He'd had haldol D in the past and didn't like that either. I hope he's compliant enough to stick with the orals...

 

[whopper]

The parts where I practice, Prolixin D is very available.

I have wondered, what do you do when you got a patient who is stable on one med and seemingly only on that one med and the manufacturer decides to stop that med? I haven't encountered it yet, but I have heard stories from some older attendings of having that happen with one of their patients--psychiatric or not.

Being that Prolixin Dec is readily available in some parts, perhaps fishing for another distributor of Prolixin D could help.