Options for clozapine-resistant schizophrenia?

[mmms85]

I have a patient on the long term ward who transferred from a local short term ward, presented with persisting persecutory delusions and command hallucinations with accompanying violence risk, dx was schizophrenia. He came in on Risperidone 4mg BID, had previously been on Haloperidol, Olanzapine, Aripiprazole, and Lurasidone, Didn't want to up the Risperdal because anecdotally I haven't seen much success with doses above 8mg.

Given he had failed multiple antipsychotics and the fact he was violent multiple times a week I decided on Clozapine, titrated him to 300mg over 3 weeks, tested plasma levels and decided to up it to 400mg and sit there. After a month saw about a 20% reduction in PANSS scores, patient was still agitated. Decided to augment with Haloperidol 10mg BID, when that failed I added Divalproex Sodium (Depakote) and titrated up to therapeutic plasma levels, no change. Swapped out the Haloperidol for 3mg Cariprazine (I wanted to try a partial agonist but patient had horrible akathisia on aripiprazole so I decided on Cariprazine,) no change after a month.

I reviewed the diagnosis, got a good history with the help of family members and sent the patient in for a neurological eval to make sure we were dealing with a psychiatric illness. I came to the conclusion that schizophrenia was the correct diagnosis, neuro eval came back normal.

I have used Clozaril a good bit as a doctor but have never had someone fail Clozaril + augmentations, so I'm basically wondering what other options I have. ECT is an option (and the patient is on a court order so he doesn't really have a choice) but I want to make sure I tick every box. Any and all advice is appreciated.

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[thepoopologist]

Questions:
Is the psychosis the sole driving factor of the violence or are their other elements driving the violence

What medications is he on now? How is he doing symptomatically and behaviorally

What was the Clozapine level at 400 mg? Clozapine/Norclozapine ratio?

Ever go any higher than 20 mg of Haldol?

How quickly did you taper the Haldol before switching to Abilify/Cariprazine?

What plasma level of Depakote did he have at what dose?

Thoughts/assumptions at the moment:
The goal of reducing violence by reducing the psychosis is generally a more conservative approach than medicating based on frequency of violent episodes alone, however I understand why the former is done.

Partial agonists are generally not going to be effective in someone like this.

ECT is the next step, but I'm assuming you wanted to review the steps you've made thus far. Most of my questions as you can see are just asking whether you've actually maximized dosing

 

[thepoopologist]

I guess while I wait for more details, I will randomly throw out the suggestion that clonidine, propranolol and the benzodiazepines are things I sometimes add for violence/agitation alone.

 

[thepoopologist]

I'm going to keep typing since I've just had a doughnut and am on a sugar high.

Your clozapine level should be 350 ng/ml to 1000 ng/ml. Any higher than 1000 risk > benefit, but 350 should be seen as minimum, not the target.
Clozapine/Norclozapine ratio may give you a rough idea of the rate of metabolism

Generally strong antagonists with depot formulations (if you find a winner) are the ones to choose here.

I asked about the Haldol taper because I was wondering how quickly that was relative to the length of the Abilify trial. Either the Haldol taper caused it, or the Abilify trial did it, of course a combination of both factors as well

 

[birchswing]

48 hour video EEG?

Just a zebra thought from a layperson, but EEGs miss things.

 

[mmms85]

Questions:
Is the psychosis the sole driving factor of the violence or are their other elements driving the violence

What medications is he on now? How is he doing symptomatically and behaviorally

What was the Clozapine level at 400 mg? Clozapine/Norclozapine ratio?

Ever go any higher than 20 mg of Haldol?

How quickly did you taper the Haldol before switching to Abilify/Cariprazine?

What plasma level of Depakote did he have at what dose?

Thoughts/assumptions at the moment:
The goal of reducing violence by reducing the psychosis is generally a more conservative approach than medicating based on frequency of violent episodes alone, however I understand why the former is done.

Partial agonists are generally not going to be effective in someone like this.

ECT is the next step, but I'm assuming you wanted to review the steps you've made thus far. Most of my questions as you can see are just asking whether you've actually maximized dosing

1. I believe the psychosis is the sole driving factor, he gets very paranoid about hospital staff working for the FBI and spying on him, so he attacks those people. The "voices" also urge him to do this.
2. He is on Clozaril 200mg BID, Depakote 250mg BID, and Ativan 1mg TID. With regards to symptoms, the last PANSS score I did he remained right around 20% reduced as compared with when he was first admitted. Behaviorally he spends most his time either sitting in the day room watching TV or pacing the halls, he has violent outbursts about 3 times a week where he'll attempt to attack either staff or a fellow patient, usually resulting in seclusion and/or a "B-52" injection.
3. Clozapine level was 632 ng/mL, Norclozapine was 275 ng/mL
4. No! But it's certainly an option. He handled 20mg Haldol quite well....no EPS besides a mild akathisia that was well controlled with Inderal, so I could push it to 30 (or even the FDA max, 40) milligrams. Haldol also has a depot preparation, which could be very useful when he is discharged.
5. I tapered by 10mg a week, introduced the cariprazine at 1.5mg, moved to 3mg after one week, so by the end of two weeks he was on no Haldol and 3mg of Cariprazine.
6. 500mg total, 250mg BID is how I prescribed it. The level was fairly high, 93 mcg/mL, even though the dosage wasn't as high as I usually push it for mania.

Some thoughts:
I could try to up the Clozaril dose...a plasma level in the 600s is high but I could bump it up higher and see if it has any effect on his psychosis. Another option would be to try higher doses of Haldol, assuming he tolerates it well.

 

[mmms85]

I could also try another high potency typical antipsychotic, like Trilafon. Not sure if the hospital keeps it on formulary actually, the only typicals I've used while on staff at this hospital are Thorazine and Haldol.

 

[psychacad]

You have room on the clozapine. I would consider that before increasing Haldol or even adding any other antipsychotic.

Are you sure about Ativan? Paradoxical disinhibition and all that.

You also have room on the depakote. What's his level? 300mg BID is a fairly small dose and depakote is a reasonable choice for impulse control.

 

[thepoopologist]

What a case!

My 2 cents, one thing at a time, but in order of priority

1. Ditch the partial agonists and restart the Haldol, especially given the command hallucinations. Increase as high as you're comfortable with, 40 mg daily sounds reasonable. As far as FDA maximums are concerned, I suppose it depends on the standard of practice at your facility. At my state facility, I start taking plasma levels above the FDA max, and as long as the plasma level isn't above 30 ng/ml (a relatively 90% D2 receptor saturation) then it justifies the dose, which I anecdotally don't exceed 60-80 mg on. The plasma level isn't necessarily associated with clinical effect, but difficult times call for difficult measures. Anyway the 40 mg daily with the intermittent B52s could be easily justified.

2. Because of the impulsive aggression, the Depakote could be uptitrated to 120 mcg/ml level, maybe monitoring for liver function, maybe ammonia + discontinuation if you're seeing confusion.

3. A clozapine increase would be next, but probably diminishing returns at the higher doses since its at a good level already

4. Definitely keep the Inderal and Ativan going

 

[thepoopologist]

Oh, and if you find a combo that's tolerable and initially shows a slight improvement. Give it lots of time, so a month or more.

 

[mmms85]

Thank you both! It certainly is quite a case...I work at a private hospital with both a long term and a short term ward, generally the people who end up in the long term ward are those who would - under normal circumstances - be admitted to a state hospital, but the state government has been decreasing beds so it's usually years of waiting to get someone admitted unless forensic factors are involved. Treatment resistant psychosis isn't rare (in the long term ward especially) but this case is certainly an extreme.

Are you sure about Ativan? Paradoxical disinhibition and all that.

You also have room on the depakote. What's his level? 300mg BID is a fairly small dose and depakote is a reasonable choice for impulse control.

Paradoxical disinhibition is certainly a possibility...I haven't given it much thought because he was severely agitated upon admission, and the Ativan wasn't started until right around two weeks in. I typed the dose in wrong for the Depakote....it's 250mg BID not 300, which is even smaller. I was taught in residency to never go above 100 mcg/mL with regards to plasma levels but I may go a bit higher with extensive liver monitoring, as thepoopologist commented.

What a case!

My 2 cents, one thing at a time, but in order of priority

1. Ditch the partial agonists and restart the Haldol, especially given the command hallucinations. Increase as high as you're comfortable with, 40 mg daily sounds reasonable. As far as FDA maximums are concerned, I suppose it depends on the standard of practice at your facility. At my state facility, I start taking plasma levels above the FDA max, and as long as the plasma level isn't above 30 ng/ml (a relatively 90% D2 receptor saturation) then it justifies the dose, which I anecdotally don't exceed 60-80 mg on. The plasma level isn't necessarily associated with clinical effect, but difficult times call for difficult measures. Anyway the 40 mg daily with the intermittent B52s could be easily justified.

2. Because of the impulsive aggression, the Depakote could be uptitrated to 120 mcg/ml level, maybe monitoring for liver function, maybe ammonia + discontinuation if you're seeing confusion.

3. A clozapine increase would be next, but probably diminishing returns at the higher doses since its at a good level already

4. Definitely keep the Inderal and Ativan going

I don't work on the weekends usually, but I think I will message the doctor who is covering this weekend and get him to begin titration from 400mg to 500mg of Clozapine, no reason to wait, as well as starting Haldol at 5mg. I'll do a quicker than usual titration, generally I start at 5mg and titrate 5-10mg a week, but given he had few adverse effects with 20mg of Haldol, I can do it a bit faster. I'll plan to get to 30mg and then check plasma, Like I said above, I'll up the Depakote, as of now he's taking 250mg BID but I think I'll do 250mg qAM and 500mg qHS. I'll write orders for weekly liver monitoring (he's already getting weekly blood taken for Clozaril, so) as well as alerting the nurses to the possibility of increased adverse effects.

With regards to plasma and institutional practice, plasma is done routinely for Lithium/Clozapine/Depakote at the hospital in which I work, although doctors can write orders for plasma testing as needed. I usually only write plasma levels outside of Lithium/Depakote/Clozaril if I'm seeing zero side effects and zero benefit at a high dose, for example, I had one patient on 30mg of Haldol and literally zero side effects. Turns out, she was a rapid metabolizer and I ended up having to get her off the medication. This current patient got akathisia from the 20mg I was giving him, so I suspect he's not a rapid metabolizer, but given the difficulties of this case I want to make sure we're blockading his D2 receptors sufficiently.

Again, thank you both so much, and feel free to keep dumping suggestions if anything comes to y'alls heads.

 

[thepoopologist]

Think about the K value/receptor affinity of Clozapine vs Haldol, and what it would mean to increase both at the same time. Haldol would take precedence in this case, just like in a case of Abilify vs Haldol, Abilify's actions would predominate when evaluating clinical effect


Also, I hope some of the smarter people in here can chime in and add their thoughts.

 

[Stagg737]

Not a smarter person but some thoughts.

Depakote level of 120 is appropriate for acute prescription. But generally 100 would be more ideal long term. As long as you’re monitoring labs regularly and he’s tolerating it, being above 100 could certainly be justified given risk v benefit.

If you’re encountering problems with patient tolerating Haldol at higher doses, you can also try Prolixin. I’ve used it a few times for acute agitation on the unit and patients have actually done quite well with it. It also has an LAI formulation if needed.

There is also some data for NMDA receptor antagonists helping for treatment resistant symptoms including as an adjunct to Clozapine. I have never done this myself, but may be worth a try if you’re maxing out other options and still not getting good results. Some links below for further reading:

Improvement of negative and positive symptoms in treatment-refractory schizophrenia: a double-blind, randomized, placebo-controlled trial with memantine as add-on therapy to clozapine - PubMed

clinicaltrials.gov Identifier: NCT00757978.

pubmed.ncbi.nlm.nih.gov

Adjunctive memantine for schizophrenia: a meta-analysis of randomized, double-blind, placebo-controlled trials - PubMed

This meta-analysis showed that adjunctive memantine appears to be an efficacious and safe treatment for improving negative symptoms and neurocognitive performance in schizophrenia. Higher quality RCTs with larger samples are warranted to confirm these findings.

pubmed.ncbi.nlm.nih.gov

 

[hallowmann]

Personally I'd focus on the clozapine and Haldol first, Depakote secondarily. I have used memantine on very treatment resistant cases with minimal benefit anecdotally, but these were bad cases to begin with. People who ultimately only got truly "better" with ECT. This does sound like an interesting and tough case, but as far as I'm concerned you are doing the things you need to and have a good plan for the future from the other posters here. Good luck!

 

[clausewitz2]

Agree with maxing out clozapine first off; levels are only meaningful if they are zero (so cheeking somehow) or above 1000 (major seizure risk). Otherwise titrate to effect/tolerability. D2 receptor binding is probably irrelevant to its actual mechanism of action. Of neuroleptics for augmentation Abilify has best evidence and reduces the metabolic side effects so if you are already using a benzo worth considering trying it again and just medicating the akathisia.

Realistically I can't imagine jacking the Haldol being very helpful given history to date. Remember, about 30% of TR schizophrenia patients don't have any apparent D2 receptor abnormalities and the problem is not really an issue of dopaminergic tone per se.

I would be looking at agents that aren't mostly dopaminergic. Lamictal has reasonable evidence as clozapine augmentation. Minocycline in general is fairly benign and is supported by multiple studies. Reserpine is also an option and has the advantage of tending to be a bit sedating of impulsive violence is the problem. Sarcosine and d-cycloserine should also go on the list.

Also though I am curious as to what the neuro evaluation really consisted of. What were the EEG findings? Were any episodes captured or was it just inter-ictal? Any CSF/blood sent for autoimmune testing?

Do you have any psychologists on staff? If the patient is spending most of their time inactive and only rarely suddenly becomes violent, something is triggering these episodes. It may be hard to arrange but a really good behavioral analysis of these episodes could be invaluable for cutting down on the violence.

 

[NickNaylor]

The Texas Medication Algorithm Project has a nice overview of the management of treatment-resistant schizophrenia. The article is behind a paywall (Psychiatry Online), but the same information can be found here: https://www.cdphp.com/-/media/files...ealth/tmap-schizophrenia-treatments.pdf?la=en. In residency, I did a psychopharmacology case conference about this exact topic and a pretty thorough literature review. This was a few years ago but I doubt that there have been any significant paradigm shifts in the evidence. You're welcome to review the "summary" handout (which is still pretty lengthy) based on the literature review here:



I agree with titrating clozapine levels as much as tolerated and ensuring that adherence isn't an issue. It sounds like you've been on the lookout for alternative etiologies which have not been revealing.

 

[mmms85]

Agree with maxing out clozapine first off; levels are only meaningful if they are zero (so cheeking somehow) or above 1000 (major seizure risk). Otherwise titrate to effect/tolerability. D2 receptor binding is probably irrelevant to its actual mechanism of action. Of neuroleptics for augmentation Abilify has best evidence and reduces the metabolic side effects so if you are already using a benzo worth considering trying it again and just medicating the akathisia.

Realistically I can't imagine jacking the Haldol being very helpful given history to date. Remember, about 30% of TR schizophrenia patients don't have any apparent D2 receptor abnormalities and the problem is not really an issue of dopaminergic tone per se.

I would be looking at agents that aren't mostly dopaminergic. Lamictal has reasonable evidence as clozapine augmentation. Minocycline in general is fairly benign and is supported by multiple studies. Reserpine is also an option and has the advantage of tending to be a bit sedating of impulsive violence is the problem. Sarcosine and d-cycloserine should also go on the list.

Also though I am curious as to what the neuro evaluation really consisted of. What were the EEG findings? Were any episodes captured or was it just inter-ictal? Any CSF/blood sent for autoimmune testing?

Do you have any psychologists on staff? If the patient is spending most of their time inactive and only rarely suddenly becomes violent, something is triggering these episodes. It may be hard to arrange but a really good behavioral analysis of these episodes could be invaluable for cutting down on the violence.

We did check for autoimmune responses, as well as testing inflammation levels. With regards to the EEG, the patient reported hearing voices at the time of the test, but was not particularly violent, there were no abnormal results during the EEG according to the neurologist who conducted the evaluation. No signs of seizure activity, abnormal bleeding of any kind, etc. Supposedly perfectly healthy.

Really good point with regards to trying to identify triggers, we have several psychologists on staff although usually they're only in the facility when conducting group therapy, at our next treatment team I'll brainstorm ideas with the team and see if we can't get something figured out.

Patient began titrating up his Clozapine dose today, I've decided to up the dose to 500mg and wait a bit, then add on another antipsychotic agent if there is not an adequate response. After we get the antipsychotic situation stabilized I'll tentatively up the dose of Depakote.

 

[brazilianpsych]

Be aware that I trained in another country. Had a lot of Clozapine patients and did a poster about refractory schizo. We had 6 patients with refractory schizophrenia in our program. I mention that because we did not have access to Clozapine serum levels, so we would use clinical improvement/side effects to alter the dosage. That being said:

- I had a lot of patients with 700mg of Clozapine without major side effects. Consider going up on Clozapine.
- Beyond Clozapine the grounds are unknown. There are articles and case reports about pretty much anything, however, nothing seems better than rest (except maybe for ECT). In my program, we had augmentation with Haloperiol, Risperidone, Olanzapine, Aripiprazole, and Chlorpromazine in different patients (not in the same patient ofc). It was pretty much trial and error because those patients were obviously very severe. That being said, this may take time. Most patients were using Clozapine + 1 anti psychotic. One patient was using Clozapine + 2 anti psychothics.

All that being said, based on my small experience (n=6), this kind of patient is very hard to treat and it may go based on trial and error.

 

[thepoopologist]

I defer to the clozapine gods. Many good points made, I always appreciate the posts here.

 

[whopper]

Yes Clozapine resistant psychosis exists. What to do? In addition to everything mentioned above.....From the mouth of Henry Nasrallah.

There is good data showing that a Clozapine/Amisulpride mixture is much more effective than Clozapine itself. I've seen this data. There's several studies backing it up. The problem is Amisulpride is not available in America. This person may have to see a psychiatrist outside the USA or the American psychiatrist has to figure out some way to get this medication into the USA. IF you know how to get this done let me know cause I've never figured it out and I've had Clozapine-resistant psychotic patients.

Consider Reserpine.

 

[birchswing]

Yes Clozapine resistant psychosis exists. What to do? In addition to everything mentioned above.....From the mouth of Henry Nasrallah.

There is good data showing that a Clozapine/Amisulpride mixture is much more effective than Clozapine itself. I've seen this data. There's several studies backing it up. The problem is Amisulpride is not available in America. This person may have to see a psychiatrist outside the USA or the American psychiatrist has to figure out some way to get this medication into the USA. IF you know how to get this done let me know cause I've never figured it out and I've had Clozapine-resistant psychotic patients.

Consider Reserpine.

I was curious about it so I googled it and it looks like as of february last year it's been available as an antiemetic in the US:

https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/209510s000lbl.pdf

Probably expensive since it's an NDA and would be off label use.

 

[clausewitz2]

I was curious about it so I googled it and it looks like as of february last year it's been available as an antiemetic in the US:

https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/209510s000lbl.pdf

Probably expensive since it's an NDA and would be off label use.

It's only approved IV in the US unfortunately. gotta order from them canadian pharmacies.

 

[birchswing]

It's only approved IV in the US unfortunately. gotta order from them canadian pharmacies.

There are some legit ones. My PCP gave me the name of one he trusts that is a real brick and mortar one, and I even did a google street view of it to make sure it was a real place, etc., and spoke to the pharmacist/owner on the phone. It seems like the FDA doesn't mind as long as you're getting non-controls and just for personal use.

 

[clozareal]

A 30% reduction in PANSS is the average that you can hope for. You are not going to get rid of the psychosis, disorganization, or negative symptom domains of schizophrenia spectrum disorders, rather reduce it to a manageable level. There is no cure for schizophrenia.

In California State Hospitals, psychiatrists tend to use much higher doses of antipsychotics than seen in the community. Not uncommon to see olanzapine 80mg/day, haloperidol of 60mg/day, units entirely dedicated to lithium or clozapine management, and lots of older first generation antipsychotics (trifluoperazine, perphenazine, and thiothixene are pretty common). Stephen Stahl consults on these treatment-resistant patients in the state hospitals and even wrote a manual for them for high dose antipsychotic use.

Here are some of my rambling thoughts:

1. You're in the territory of less studied options. There are a couple of studied clozapine augmentations that aren't other antipsychotics. Memantine is one option. Another option is omega-3 fatty acids.
2. An FGA + mirtazapine is thought to duplicate the receptor impact of clozapine and could be helpful, but given that clozapine has already failed your patient, the chances of success are reduced.
3. Another interesting option is an SGA + celecoxib since inflammation is thought to be related to schizophrenia pathogenesis, but the effectiveness was mostly in patients who had been ill for less than 2 years. Aspirin had a small effect too. For those who have chronic symptoms, the inflammation has probably subsided and the damage already done.
4. You can try the non-D2 acting, 5HT2A antagonists like lumateperone and pimavanserin. I've also seen some psychiatrists be partial to loxapine when other antipsychotics have failed.
5. Consider pharmacogenetic testing to look see if they are a rapid metabolizers which means you might need to use higher doses of those antipsychotics. Not relevant in your case for clozapine because you got serum levels but may be helpful with others, particularly augmenting agents.
6. You can also try targeting the negative symptoms with an SSRI.
7. Finally, you can consider clinical trials for treatment resistant schizophrenia. There are really limited options unfortunately for this condition. It's a shame more treatment-resistant cases aren't in clinical trials because in my opinion, the really severe cases are the ones that can benefit most from these trials. Also a shame there aren't more trials looking into this.

 

[Stagg737]

You can try the non-D2 acting, 5HT2A antagonists like lumateperone and pimavanserin. I've also seen some psychiatrists be partial to loxapine when other antipsychotics have failed.

Pimavanserin did have the concerns regarding increased risk of sudden death. I realize that the FDA concluded that there was no increased risk of death d/t the medication alone, but still a bit concerning and something I think about when considering it.

Anecdotally I have a couple patients on Caplyta and they seem to love it. Initial phase 3 studies were fairly promising with the lack of EPS or cardiac effects as well as the lack of (short-term) metabolic side effects. Obviously needs more data, but from what I've looked into it seems like it may become a more promising option in the future and something worth a shot (maybe before Clozapine) for more treatment resistant patients.

 

[whopper]

There's evidence based data for the safety and efficacy of antipsychotics above their FDA recommended dosages. E.g. the manufacturer of Zyprexa even recommended to the CATIE trial investigators to give out Olanzapine at 30 mg daily and at that dosage it was found to be safe at that dosage in CATIE. I used to work in Ohio and the state government's hospitals had guidelines with a large body of data backing it's use up to 40 mg daily. I've also seen several patients do better on dosages above 20 mg daily.

But I figure if a patient is being put on Clozapine they were already likely tried on several antipsychotics at above FDA recommended dosages. I would at least do that before I switched them to Clozapine.

The main problem I have with Clozapine isn't the scary side effects, but that patients or labs are not compliant enough to maintain it. There's been a move by people in academia (I know, and I know the guy who pushed for it) to fall in love again with Clozapine and not to be scared of it, even recommend it much sooner in their treatment algorithm.

From my experience I wouldn't do it. Most patients I know aren't compliant enough for the weekly then biweekly and then monthly testing. Further several labs do not cooperate with the doctor's office with the level of dedication needed. E.g. for weekly patients even if they are compliant the lab might not get you the results for several days after the testing. In my private office, every weekly patient was a headache. They'd call and we'd call the lab and sometimes not get the results till 4 days after the patient did it. Some of those calls understandibly were frantic. Then the patient would recall us again and again, and we'd recall the lab again and again. Seriously 1 patient-1visit could be 3 hours of work per week when in the weekly testing schedule. When you call the labs they don't put any more emphasis on a CBC/diff lab for a Clozapine patient anymore than they do anyone for any other lab however trivial and put you on hold for several minutes.

Unless you're a psychiatrist attached to a hospital system and the labs are being done there, so the results are in the computer within the same day, the non-medical bureaucracy limitations make Clozapine very unrealistic as a treatment option. Then add to the problem several pharmacies I've seen do not check the Clozapine registry. E.g. they'll demand proof of the lab and I tell them it's already in the registry just check it out and then they want a fax of the lab results and won't check the registry. So we fax them, and the pharmacist doesn't check out and verify he's received it sometimes for more than a day. The up to 4 day lag plus a slow pharmacist leaves no comfortable breathing room. The fault is not the medication itself but the system. The USA is the only first world country in without a unified medical record system.

Aside from being in a hospital system the only other treatment setting is the patient having a case-manager or already on the monthly schedule and they have a history of being compliant with it. The case manager can then be stuck with the grunt-work of contacting all the entities to get the medication out. Still bad but at least then you're headache is less. Otherwise Clozapine is a pain in the butt cause every single week you're going to go through the headache again and again and again of being like WHERE THE EFF ARE THESE PATIENT'S LABS? OH WE HAVEN'T RECEIVED IT AGAIN? CALL THE PATIENT UP. OKAY THEY ALREADY GOT THE LAB? CALL THE LAB. OKAY NOW WE GOT TO WAIT 3-4 DAYS FOR THE LAB RESULT AND THE PATIENT KEEPS CALLING SCARED THEY'LL MISS THEIR NEXT PRESCRIPTION. YOU CALLED THE LAB 5X AN THEY STILL HAVEN'T FAXED IT YET? OK WE GOT THE LAB? THE PHAMACIST WON'T CHECK THE REGISTRY AND WANTS A COPY OF THE LABS HIMSELF. OKAY WE FAXED IT BUT HE HASN'T TOLD US YET HE RECEIVED IT! PATIENT KEEPS CALLING US UPSET ABOUT THIS!


Imagine going through the above headache every freaking week for 6 months! Then biweekly!

I would only recommend Clozapine for a patient that's tried at least 5 antipsychotics and with at least 3 being of differing chemical backbone structures or liver enzyme metabolites.

 

[mmms85]

Just wanted to update y'all on this.

Patient was discharged to family last week, I ended up switching the Haloperidol for Fluphenazine and raising the Clozapine dosage to 600mg. Fluphenazine was titrated to 20mg and positive symptoms lessened, when the positive symptoms began to remit the patients aggressiveness remitted as well. I slowly titrated the patient off the Ativan and elected to continue the Depakote and Inderal.

Before discharge - after talking it through with the patient - I opted to switch from oral Fluphenazine to Fluphenazine decanoate, the dosage being 25mg every 3 weeks.

The patient was referred to the local CMHC, where I know for a fact they do clozapine and also do a large amount of LAI's.

 

[robellis]

Just wanted to update y'all on this.

Patient was discharged to family last week, I ended up switching the Haloperidol for Fluphenazine and raising the Clozapine dosage to 600mg. Fluphenazine was titrated to 20mg and positive symptoms lessened, when the positive symptoms began to remit the patients aggressiveness remitted as well. I slowly titrated the patient off the Ativan and elected to continue the Depakote and Inderal.

Before discharge - after talking it through with the patient - I opted to switch from oral Fluphenazine to Fluphenazine decanoate, the dosage being 25mg every 3 weeks.

The patient was referred to the local CMHC, where I know for a fact they do clozapine and also do a large amount of LAI's.

Great work!

 

[comp1]

I'm surprised at how people quickly jumped to zebras like medical causes...in my experience, clozapine resistant schizophrenia isn't that rare. It's got to be at least 10%, maybe more.

 

[FlowRate]

Just wanted to update y'all on this.

Patient was discharged to family last week, I ended up switching the Haloperidol for Fluphenazine and raising the Clozapine dosage to 600mg. Fluphenazine was titrated to 20mg and positive symptoms lessened, when the positive symptoms began to remit the patients aggressiveness remitted as well. I slowly titrated the patient off the Ativan and elected to continue the Depakote and Inderal.

Before discharge - after talking it through with the patient - I opted to switch from oral Fluphenazine to Fluphenazine decanoate, the dosage being 25mg every 3 weeks.

The patient was referred to the local CMHC, where I know for a fact they do clozapine and also do a large amount of LAI's.

If they luck into a really good outpatient psychiatrist it sounds like they may be able to pull off the clozapine longer-term. We had a couple of senior and well respected (at MMHC for 40 years) attendings who always made a point of recommending that when you're treating resistant psychosis and working through 2-antipsychotic combinations it's often the most recently added one that's actually effective, not the combination of the two.

 

[deleted1100659]

If they luck into a really good outpatient psychiatrist it sounds like they may be able to pull off the clozapine longer-term. We had a couple of senior and well respected (at MMHC for 40 years) attendings who always made a point of recommending that when you're treating resistant psychosis and working through 2-antipsychotic combinations it's often the most recently added one that's actually effective, not the combination of the two.

I agree with this 100%. I was lucky to work with someone who is considered to be quite the expert on clozapine, and all the time he would push the clozapine up, and mainly go off therapeutic response more than anything.

Depakote 250mg BID I wonder if that was doing anything at all.

my own personal thought process would have been to titrate clozapine, as you did. Also I dont know if hes a smoker or uses any substances.

Personally I think clozapine is a great drug, works wonders. But the obvious drawback is it requires some form of accountability, meaning needs to be caregiver involvement, someone you can trust, otherwise it will just be a complete mess. A lot of my higher acuity pts don't have the best caregiver involvement..

In severe patients, I have found ECT or clozapine to be the best bets. Everything else seems hit or miss