Big antipsychotic doses

Discussion in 'Psychiatry' started by heyjack70, Aug 11, 2015.

  1. heyjack70

    heyjack70 Junior Member
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    clozaril 500 mg bid.
    Zydis 50 mg bid.
    Lithium 450 qam, 900 mg qhs.

    Anyone ever see the need for such doses? Maybe at a State hospital?
     
  2. Wilf

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    No, and lithium isn't an antipsychotic. That's cute that you say big instead of high dose.
     
  3. birchswing

    birchswing Patient/Interested in Psychiatry
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    Not as cute as baby aspirin.

    Neither big nor high is literal. Maybe weightier? Put him on a weighty dose, 500 mg.

    Outside of Earth, we'd have to call it a massy dose.
     
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  4. shan564

    shan564 Below the fray
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    Zyprexa and clozaril undergo similar metabolism, so maybe the patient is just a fast metabolizer. They're both metabolized much faster in people who are heavy smokers - I have a patient who had a clozapine level of <100 despite being on 500mg a day, and his caregiver insists that he's been compliant - I was tempted to increase his dose, but he had urinary retention that was compounded by BPH.

    That lithium level isn't too bad.
     
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  5. wolfvgang22

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    Flame post removed. Realized I'm not Trump.
     
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    #5 wolfvgang22, Aug 12, 2015
    Last edited: Aug 12, 2015
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  6. heyjack70

    heyjack70 Junior Member
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    You're being a jerk. Thanks for nothing.
     
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  7. milesed

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    Lithium dose should be within appropriate lab level. I haven't used the AP's you listed at those doses, but have used others outside of "approved dosages" as well as more than 1 at a time. Depot is usually done first to ensure they are getting it if available.
     
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  8. Doctor Bagel

    Doctor Bagel so cheap and juicy
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    Might be interesting to get a level at least on the clozapine. I'm not super experienced and haven't seen doses that high for olanzapine and clozapine, certainly not in combination. I have seen really high levels of olanzapine, though, which I think is often related to trying to push more effect than you can really expect in too short of a time. Consequently I'd think of it as less of a state hospital thing and more of a inpatient unit thing where you're trying to get super psychotic and agitated people stabilized in a few weeks. I'm not entirely sure about the true efficacy/safety of this, but yeah, I've seen it.
     
  9. wolfvgang22

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    Clozapine and olanzapine together is awfully redundant.
     
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  10. whopper

    whopper Former jolly good fellow
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    I've seen patients on 5 meds at the same time not because the polypharmacy was unneeded but because it was highly needed. E.g Clozapine 500+ mg, Depakote, Haldol, Cogention, and Lithium.

    I've never seen this type of phenomenon happen that was legitimate until I worked in a state hospital where we literally had guys that killed other people while psychotic. Short term units usually get rid of these people and send them to the state hospitals cause they can't handle them. But when you're in a state hospital, you get all of the worst of the worst that no other hospitals in the state could handle.

    So a state hospital, for example, could literally have the worst treatment resistant patients in an entire state or a large region of it.

    And the horrific irony is that so many of the docs I've seen in state hospitals are horrendous. These are the worst patients ever and need the best docs to treat them and here we have a doctor that won't do the court-ordered meds cause he doesn't feel like spending 20 minutes to write up the court report so the patient stays psychotic for months without treatment when it could've just been a few days.

    If you see a patient on big mega-dosages of a lot of meds it either means the patient really did need them or the doc treating the patient is a polypharmacist idiot that just medicates everyone on everything cause he really doesn't know what he's doing.
     
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  11. Ceke2002

    Ceke2002 Purveyor of Strange
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    I've seen both sides of the coin from a patient's point of view as well. There were a couple of friends who were placed on multiple medications, some at what I'd consider higher than needed doses (like 800 mgs of Seroquel on top of an unknown dose of Olanzapine, two different antidepressants and a mood stabiliser to treat BPD, with zero psychotherapy given), who then did a lot better when they transferred treatment to a different Psychiatrist and were finally placed on the one or two medications they actually needed, titrated to a properly individualised dosage, with psychotherapy forming a regular part of their treatment as well. And then there was one friend who was basically placed in chemical restraint with the amount of APs and mood stabilisers they had him on when he was in the State Hospital, but in his case it was a necessity because by the time he was admitted he was usually so violently manic it wasn't uncommon for him to literally start breaking people's bones at the slightest provocation (at least one admission, before they managed to get enough meds in his system, he snapped a nurse's forearm and fractured an orderly's skull).
     
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  12. shan564

    shan564 Below the fray
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    Check a clozapine level, and I'll bet it'll be nontoxic. And olanzapine is metabolized similarly, so the clozapine level will also be a vague proxy of the olanzapine level. If the patient isn't a rapid metabolizer, I'd expect him/her to have developed some anticholinergic toxicity by now (probably urinary retention and constipation, especially with the extra serotonergic constipation from clozapine).
     
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  13. digitlnoize

    digitlnoize Rock God
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    I've had patients on Lithium 600/900 with a blood level of 0.8-1.0. No big deal. The Zyprexa/Clozaril combo seems a bit odd, but you never know, especially if a state hospital was involved.

    The worse polypharm I ever saw was this (on a new female patient who just moved to my area):

    - Ambien 20 mg nightly
    - Clonazepam 4 mg nightly
    - Seroquel 50 mg nightly
    - Lithium 150 mg daily (she was told she was "bipolar")
    - Celexa 10 mg daily
    - Wellbutrin 150 mg daily

    In about 4 months I got her switched over to this:

    - No Ambien (!)
    - No Clonazepam (!!!)
    - Seroquel 150 mg QHS
    - Trazodone 100 mg QHS
    - Lamictal 200 mg daily (just in case, I still don't have records from her old doctor, there's a very slim chance that she had one manic episode 20 years ago...)
    - Celexa 20 mg daily
    - No wellbutrin.

    She's doing much better.
     
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  14. Shikima

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    You know what's more amazing? That we've neutered state systems for this reason. I suspect there are a lot of people out there who would beenfit from this service which end up in a revolving door admission state or in jail/prison sequence.
     
  15. whopper

    whopper Former jolly good fellow
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    IMHO my own greatest strength in psychiatry that came the easiest to me was inpatient and treating very difficult treatment-resistant patients. So one might think I should work in a state hospital. Maybe. The problem was that everyday I was there I had at least a few hours of day of being infuriated with the other docs who literally where doing almost nothing and in many cases making the patients worse.

    I literally had about 5 hours a day with nothing to do in the hospital because once I cleared many of these patients up I couldn't discharge them. I had to wait for a judge to do that and even if I called/wrote the judge to discharge ASAP they wouldn't do so for months. So in the meantime I had a unit full of patients stabilized and I had nothing to do other than write the perfunctory note saying they were fine that really had no differences 95% from the previous note so I was just copying and pasting.

    This made me even more upset with the do-nothing doctors cause if you did your job right it still was easy. In fact too easy for me. I was dreading the free-time where I had nothing to do but was forced to stay on hospital grounds 40 hours a week.

    I placed a set of dumbells in my office, a laptop where I could watch DVDs and caught up on HBO's Deadwood. I started painting D&D metal miniatures.

    After about 6 months of doing this, the CCO noticed I was getting people out faster and took my stabilized patients out of my unit and gave me all the patients from the do-nothing doctors, that I all stabilized in about 1-4 weeks, and some of these patients were psychotic for several months if not a few years with no success. I became resentful because I was getting no more pay for this better performance and because we were getting some of the worst other patients in the hospital (10 units, 25 beds each and remember these are the worst patients in the state), it was getting dangerous for my treatment team at times.

    I'm not claiming to be some genius doctor. I do think I'm an excellent inpatient doctor but it was me in comparison with others like a guy that literally would take a person off all her meds (that had severe schizoaffective disorder) and when the patient was attacking other patients, and when staff members demanded he inject the patient, in a thick Polish accent he'd refuse and say "let her be free!"

    Add to the anger this was someone I just stabilized and she was switched to this other doctor.

    My wife told me that I needed to stop being angry every time I came home or I had to stop that job. I stopped that job cause if I didn't get angry, I felt I'd be accepting the less than mediocre performance of the other doctors. I was also mad that my performance was so much better but they wouldn't pay me anymore.

    After I left about a year later my old boss (and a good friend of mine) offered me to come back offering $40K more than the usual state doc pay. Docs with the state are paid based on an equation but he told me he argued with someone in the governor's office that I was exceptional and that I was literally saving the state millions cause I was getting the patient out of the hospital with some speed while the other docs, many of them had, had no speed.

    About 1 year later I was offered the #2 physician's position in that state hospital. I turned it down cause I moved to St. Louis.

    The point of all this is that state hospitals (like the VA) have so many problems that could be easily fixed and in effect save these hospitals money. IMHO paying psychiatrists more in state hospital but expecting results would do so and getting rid of the do-nothing doctors could then be done because if the salaries were competitive new doctors would take the jobs. What was going on was the salaries for docs in that state job were 30K below the average. The staff members had a saying at the hospital. "All the good doctors leave in about 3 years, and all the bad doctors stay." It's not completely true. I do know a few good doctors there that have been there several years but they are the minority.

    (And I hope some things have improved because I do know they did increase salaries and the new CCO there is much better than the previous one).
     
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    #15 whopper, Aug 13, 2015
    Last edited: Aug 13, 2015
  16. Shikima

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    @whopper - Fallout shelter is now out for the Android device.
     
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  17. smalltownpsych

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    The other examples of polypharmacy I see are for Borderline personality disorder and for substance abusers. For these two categories you can almost arrive at a diagnose for the patient just by seeing the list of their meds. That list you had for the psychotic patient would not be the right list. It would be more like: xanax, seroquel, adderall, and maybe an opiate for good measure or: geodon, lithium, depakote, seroquel, ativan, xanax, vistaril, . Guess which list goes with which dx.
     
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  18. Shikima

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  19. whopper

    whopper Former jolly good fellow
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    I medicate borderlines with 1-2 meds only. Nothing is a medication of abuse. E.g. Seroquel 150 mg cause there's an actual study showing it can work at that dosage for borderline PD, and I emphasize that meds really aren't the main treatment with this disorder and refer them to a DBT therapist.
     
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  20. Wilf

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    Can you share some of the ways that you are able to clear up these sickest of patients? At the hospital here, which feeds quit a few patients to the state hospital, we have patients who even on high dose clozaril or combos of neuroleptics continue to be psychotic.
     
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  21. smalltownpsych

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    Great question. I imagine some of whoppers efficacy is also due to psychological factors though. Dealing with bad doctors upsets everyone and when psychotic patients get upset, they get more psychotic.
     
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  22. whopper

    whopper Former jolly good fellow
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    Amisulparide is the only antipsychotic that's been found, when mixed with Clozapine, to consistently successfully treat Clozapine resistant patients. There is a lit-review published where other meds were tried and pretty much each one had it's fair share of successes and failures but no consistent consensus that the other meds worked.

    Problem is amisulparide is not available in the US.

    One could, however, request the DEA to have it brought in in special cases. Edit-Or is it the FDA? It's one of them.
    https://en.wikipedia.org/wiki/Amisulpride

    Aside from this ECT, augmentation with Depakote or lithium, addition of antipsychotics of highly differing structures to the Clozapine. As mentioned above if Clozapine fails get blood levels of Clozapine and norclozapine. Also consider genetic testing to see if they're a hyper-metabolizer or if the genes just suggest the med won't work.

    If these fail consider Reserpine.

    Another thing. I had a patient that did respond to antipsychotics but only after several weeks. That said the "late responder" to antipsychotics doesn't hold up in studies.
     
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    #22 whopper, Aug 13, 2015
    Last edited: Aug 14, 2015
  23. splik

    splik Professional Cat at Large
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    also most psychotic patients will get less psychotic if you stop chucking drugs at them which probably make them more psychotic. In the pre-thorazine era most of these patients were discharged as recovered after 1 year.
     
  24. heyjack70

    heyjack70 Junior Member
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    Late responder doesn't hold up?
     
  25. splik

    splik Professional Cat at Large
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    the data suggest that typically if pts don't respond at all in the first week they likely never will
     
  26. whopper

    whopper Former jolly good fellow
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    I did see a few patients respond late so I didn't know what to make of it. Some patients defy the studies but until all the conventional steps are taken and ruled out we shouldn't put too much stock into the very rare possibilities.

    When I couldn't tell what was going on with a patient I wouldn't medicate them and check them out while unmedicated. These figures aren't scientific but from memory and experience about 70% of the time I had it figured out the first day, 90% of the time by day 2 and 99% of the time by day 3.
     
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  27. smalltownpsych

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    That's one problem with our research. Even if 90% of the patients were to respond to a specific treatment, that still means we don't know what to do about the 10%. It always seems like I get the outliers, too! I also like your patience with medication trials and diagnosis. It always seems like we get a lot of pressure to have the answer - today; whereas, observations over time and in different contexts is often necessary.
     
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  28. whopper

    whopper Former jolly good fellow
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    We had a guy in the state hospital that was a late-responder. Took about a month for the meds to work. It was to the point that the veteran nurses knew it almost to the day that he'd clear up.

    So I do think late-response does exist, just that if you pubmed it studies don't back it up. In medicine there will always be some patients that don't match the studies. Always start with the conventional but start being creative only when all the conventional stuff has been tried and failed or you see reason to think this case is really out of the ordinary.

    I'm still at a loss with STEP-BD, the very well done study showing that antidepressants don't help in bipolar depression. All my patients with bipolar depression, I stopped their antidepressant and they became depressed. So I restarted their antidepressant and their depression went away. Most of these people I witnessed the mania myself so I knew they had bipolar disorder.
     
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  29. heyjack70

    heyjack70 Junior Member
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    Brief update: clozapine level was zero.
     
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  30. smalltownpsych

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    Discontinuation effects or even placebo effects. Have we ever really looked at the placebo effect related to stopping something the patient believes is working? I know that we run into variations of this all the time when patients reports don't match up with the actual effects of the medication. "I forgot to take my Prozac today and I feel so depressed."
     
  31. whopper

    whopper Former jolly good fellow
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    You're correct. It could've been placebo-effect too.
     
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  32. splik

    splik Professional Cat at Large
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    I think the role of antidepressants in bipolar depression is complex. They key points most everyone can agree on are that 1) antidepressant monotherapy should not be used in bipolar I disorder and 2) avoid TCAs as far as possible. One of the problems with STEP-BD is that most of the patients were receiving some form of psychotherapy so it's possible that that cancelled out any antidepressant effects vs placebo (but also makes the case that psychotherapies are underutilized in bipolar pts).

    Bipolar pts get very attached to their "antidepressants" and it's been argued part of the power is because they have been misleadingly named antidepressants and patients want to take an antidepressant and not a "mood stabilizer" so when you remove it they don't think they have been adequately treated.

    I think the most interesting shift in recent years is it's become clear that in bipolar II antidepressant monotherapy is perfectly fine for many patients and a lot of the literature discrediting antidepressants as inducing switching and other general badness was probably all part of the rhetoric to get people to move from generic antidepressants to patented antipsychotics. and what a success that has been.
     
  33. whopper

    whopper Former jolly good fellow
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    I mentioned this before in an old thread. My own theory is STEP-BD is that bipolar disorder patients become depressed for two different reasons. 1-They become depressed just like anyone else does. E.g. too many bad stressors at one time and they keep on going on to the point where the person is worn-down. To think that bipolar disorder would make you somehow invulnerable to depression is ridiculous.
    2-Such patients could also become depressed due to a cycle of their disorder that has not much to do with the psychosocial but more the biological. We can't refute that the cycling has a biological basis (but of course some of it is due to environment).

    IMHO bipolar disordered patients depressed due to reason #1 should respond to antidepressants, and perhaps #2 not so much. Just a theory but I can't think of why STEP-BD showed no significant results with antidepressants and it's one of a few theories including the ones already mentioned above as to why antidepressants didn't seem to work in that study.
     
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  34. smalltownpsych

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    Maybe because the type one depressed patient tends to respond more to psychotherapy than medications and in the STEP-BD many of the patients were receiving it.
     
  35. thoffen

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    The D2 blockade from 50 BID of Zydis is nothing compared to 30 of Haldol, and nothing even still compared to 10 of Haldol. Tolerance is mediated by other receptors. People seem to see these drugs as horse tranquilizers, but 60% of zyprexa treated patients do not report sedation. It's true that you can knock someone on their rear with these drugs, but you might not really make them feel differently at all as well.

    That dose of clozapine is high, but obviously the patient isn't taking it. Even still, it might not be supratherapeutic. Thankfully you can take a level. Clozapine though is a lot more likely to produce significant SE/AE when elevated (orthostasis, delirium, seizure, etc.).
     
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  36. caffeinatedresident

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    Sorry to if this not the best place to post this (as these aren't whopping antipsychotic doses), but since some of you seem pretty knowledgeable, was wondering if anyone might be willing to give some curbside advice that would be very helpful and much appreciated. Family member w/ early onset Alzheimer's w/ much increasing agitation over the past months, had been on 125 mg seroquel daily plus nameda, aricept, lamictal. Developed new onset insulin resistance with glcs to 500s thought to be 2/2 seroquel. Primary neurologist + PCP + new psychiatrist = ongoing discussion and disagreement about med management. Eventually outcome seemed to be: stop seroquel & aricept abruptly, and in their place start aripripazole and nuedexta (for pseudo bulbar effect?)? I'm questioning stopping the seroquel so abruptly (has had significantly increased agitation) and whether those new meds seem appropriate. Thoughts? Any comments would be much appreciated.
     
  37. nitemagi

    nitemagi Senior Member
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    Tapering is always appropriate, rather than stopping abruptly. Agitation can be multifactorial, esp in alzheimer's patients. Look for other things like sleep changes, constipation (nothing makes you more irritable than when you can't poop and can't communicate that to people).
     
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  38. splik

    splik Professional Cat at Large
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    sorry you are going through this. early onset dementias are particularly rough :( and probably explain all this polypharmacy (we often feel especially helpless with younger patients and think we have to do "everything"). sounds like a case of too many cooks spoiling the broth. why does she need a neurologist and a psychiatrist. at this point one will most likely suffice. IMHO neurologists are best placed to be involved in the initial diagnosis of early onset dementias but psychiatrists (geriatric psychiatrists or neuropsychiatrists not general psychiatrists) are usually much better placed to deal with the behavioral and psychological symptoms and ongoing management.

    personally i taper aricept off over the course of a month (drop to 5mg then stop) as anecdotally abrupt stopping may lead to a noticeable cognitive drop.
    whether to cross-taper from one antipsychotic to another is up for discussion. sometimes it is fine to stop one and start another. abilify has a long half-life so takes two weeks to reach steady state so i may be more inclined to cross taper rather than having stopped one or started another...

    i have to say i am not convinced it is a good idea to give dextromethorphan to people with dementia. SSRIs are still the treatment of choice for pathological laughing and crying.
     
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  39. caffeinatedresident

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    Thanks for your replies, I really appreciate it. Family member's condition has rapidly declined over the past 6 months (with significant cerebral atrophy seen on MRI, including frontal involvement) , with rapid increases in seroquel dosing (0 to 150mg over 6 months) secondary increasingly frequent and severe agitation and violent behavior. Placed in assisted living one month ago, hospitalized a few days ago for insulin after polyuria (initially started treating for UTI, w/ continued polyuria, with spot glucose check revealing glucoses in the 500s). Thinking the glycemic issues were 2/2 to his seroquel (insulin resistance, plus eating a lot more as a side effect), his primary neurologist wanted to stop it (as well as the aricept), and requested the aid of a psychiatrist, which led to the recommendations for aripripazole and nuedexta.

    My primary concern is with the abrupt stopping of his seroquel (as well of his aricept), since he had already been having increased agitation at the assisted living facility which has only increased at the hospital. It's been getting worse, keeps trying to rip out his IV and calling family members 50+ times/day to take him home (only my mother is there, I'm across the country for residency). I also admit to not understanding the rationale behind the nuedexta as he has no pseudo bulbar symptoms; in fact, I'd prefer laughing and crying to sheer rage that he has had and continues to have (i.e. breaking doors, smashing items, threatening specific people).

    I wish I could've been involved in these discussions since this information is all secondhand and apparently the three physicians involved in his care (primary neurologist + PCP, and new psychiatrist) were all in disagreement with each other. His meds seem far from optimal at this point. I'd personally be ok with continuing the seroquel and implementing glycemic control via insulin at his assisted living facility; while he still wasn't optimally controlled on it, he's been worsening and becoming more unstable off the seroquel (now off for >24 hours). He's hospitalized in a small community hospital closest to the assisted living facility and I don't think there's sufficient in-house resources there for active thoughtful psych med management, especially since he's a on general medicine service.

    If anyone else may have medication recommendations, or resources to recommend for learning more about med options, please let me know. Thanks again for your help, it's desperately appreciated. As a peds resident, this is very much outside my area of expertise, and I value any and all advice. Sigh, it's been tough arranging care from afar. I've been on inpatient / ICU rotations for the past 6 months and using my golden wknds to fly across the country every month to help, but it's been challenging....so yes, thanks for your help!
     

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