randomdoc1

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At my job I've inherited some of the more complex cases after someone in my hospital system left. It is a population of veterans who get intensive case management and a number of them are diagnosed with treatment resistant schizophrenia/bipolar disorder. Classically, I was taught that if someone fails two antipsychotic trials, it is not unreasonable to consider clozapine and there is not much evidence for multiple antipsychotics. However, a number of my new vets are on 2 antipsychotics and possibly up to a couple of mood stabilizers. Does anyone have any recommended reading on this or are familiar with antipsychotic combinations? I hear abilify with seroquel just makes no sense, and fortunately I have not seen anyone on that combination. But I'm more used to treating bread and butter depression and anxiety. It's been awhile since I managed these types of cases. I'll be doing some reading of my own but was wondering what other's people's experiences were. Thanks!
 
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thoffen

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I hope you are suggesting that some patients have treatment resistant schizophrenia and others have treatment resistant bipolar disorder, not that you are talking about patients who have both diagnoses. Some thoughts:
1. for SCZ, yes 2 failed adequate trials of antipsychotics is considered appropriate for clozapine, but that is far from a hard/fast rule. Still, it is vastly underutilized. A lot may have to do with the logistics of making the treatment happen with the blood draws.
2. BPAD is a whole other can of worms, too complicated in my view to create a general recommendation
3. Evidence for combining multiple antipsychotics or multiple mood stabilizers to my knowledge is thin at best, although studies on multiple antipsychotics have neither shown clear benefit nor clear risk. Still, the Joint Commission requires documentation of justification of multiple antipsychotic use.
4. These mental illnesses are often hard to treat, and a great number of patients may show no or limited treatment response to any medication

Most importantly, though, is to address the validity of the diagnosis itself. Or to focus the treatment plan on things other than medications which might be the more important component of successful treatment anyway.
 

wolfvgang22

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Many of my VA patients are the same type population. I also inherit patients on odd medication combos sometimes.

A lot of your patients may not be on Clozapine because of the strict monitoring requirements and the extra paperwork the VA requires for everything, especially Clozapine. It's not so much the frequent labs you would do anyway with Clozapine but all the extra paperwork and the large number of patients at the VA. This sometimes frustrates doctors into suboptimal prescribing patterns to avoid burnout and death by paperwork (ok, digital paperwork). One more set of forms and 24 button click order sets are often one too many. For me, I would quit before this happens.

Also, many of these patients won't come back to clinic as scheduled no matter how many times I or the other staff call them, and there is enormous pressure to prescribe something to help our heroes in the VA. So I think this is one reason you see veterans on 33 medications with only moderate improvement a lot of times.
 
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PistolPete

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At the state hospital where I'm working, I've had good experience combining Haldol with Zyprexa for cases that have only had partial remission of psychosis on one anti-psychotic alone and can't/won't do clozapine. I don't like polypharmacy but sometimes it is needed in a minority of patients.
 
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nitemagi

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I always add to "check your math." Meaning make sure medical mimics have been ruled out (we are physicians first, after all), and make sure to the best of your ability that the records confirm real trials of each medication.

The most important rule of thumb -- if you don't look for it, you won't find it.
 
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wolfvgang22

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At the state hospital where I'm working, I've had good experience combining Haldol with Zyprexa for cases that have only had partial remission of psychosis on one anti-psychotic alone and can't/won't do clozapine. I don't like polypharmacy but sometimes it is needed in a minority of patients.
I sometimes utilize PRN haldol for break through psychosis for patients on zyprexa in these types of cases.
 

Crayola227

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SmallBird

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At my job I've inherited some of the more complex cases after someone in my hospital system left. It is a population of veterans who get intensive case management and a number of them are diagnosed with treatment resistant schizophrenia/bipolar disorder. Classically, I was taught that if someone fails two antipsychotic trials, it is not unreasonable to consider clozapine and there is not much evidence for multiple antipsychotics. However, a number of my new vets are on 2 antipsychotics and possibly up to a couple of mood stabilizers. Does anyone have any recommended reading on this or are familiar with antipsychotic combinations? I hear abilify with seroquel just makes no sense, and fortunately I have not seen anyone on that combination. But I'm more used to treating bread and butter depression and anxiety. It's been awhile since I managed these types of cases. I'll be doing some reading of my own but was wondering what other's people's experiences were. Thanks!
When you say treatment resistant - do these patients continue to have unambiguous psychotic or manic symptoms despite being on antipsychotics, or are they struggling with disabling psychosocial adversity and substance abuse. Multiple antipsychotics probably aren't sensible in either case but are frequently applied to the latter which is particularly insane.
 
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HarryMTieboutMD

Briefly:

1) Treatment resistance schizophrenia: This presupposes that all antipsychotics (besides clozapine) work by blocking D2 to treat positive symptoms, and based on the aggregate of data, they are more or less equally efficacious (though in real life this isn't always the case). Thus, failing to respond to one AT ADEQUATE DOSE/DURATION AND COMPLIANCE is technically treatment resistance. There isn't really a rationale for "two failed antipsychotics" other than side effect burden from Clozapine. The seminal paper that got clozapine re approved was done in the 1980s by John Kane in which he watched people fail on Haldol (adequate dose/duration) and then respond to clozapine: Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. - PubMed - NCBI.

If they fail to respond to clozapine (again, adequate, dose/duration/levels/compliance) there is some evidence for augmenting with D2 blocking antipsychotics, but in reality your go to should be ECT

With a few exceptions, dual neuroleptic therapy is in general poor practice, and 90% of the time it is done by lazy psychiatrists

2) Treatment resistant bipolar isn't really as consistent, but you can conceptualize treatment resistant mania and TRD as heuristics for very difficult to treat cases.
For treatment resistance mania there is some evidence for clozapine and of course ECT

3) For treatment resistant bipolar depression... the literature is pretty vague (as it is for TRD because it's a heterogeneous syndrome), but if the patient doesn't respond to Lithium/Latuda/Seroquel you need to do ECT
 
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NickNaylor

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I did a pretty thorough lit review of treatment-resistant schizophrenia and all of the studies that I could find related to management of treatment-resistant schizophrenia for a VA case conference last year. If you're interested, you can check it out here:

https://app.box.com/s/zhntzgxtw9aaivs4p78ighbcs1votkto

As I mention there, I didn't include the references because there were too many and I had to print about 40 copies of this thing, but I can dig something up if there's a specific paper you'd like.
 
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