Advice on multiple antipsychotics in an acute setting

[Tangerine123]

PGY2 here. My experience has basically mostly been with depression addiction until now. I've been rotated to an acute ward and have more exposure now to psychosis (and obviously antipsychotics).

I'm having issues understanding the correct use of antipsychotics. Every attending has their own take on the subject and all of the sources I read postulate their own opinions and algorithms. Here is one of my current patients, with whom I'm having problems understanding how to proceed. As, I have the feeling, that we are managing him incorrectly.

Young patient with a known Schizoaffective disorder. He has been admitted multiple times, and had treated with Aripiprazol and lithium during his last stay (there's a long list of what he has had in the past). Due to extremely bad compliance, he decided to stop taking them abruptly.

He was readmitted because he developed imperative acoustic hallucinations. He was then started on Cariprazine 3mg/d because according to him, it was what helped him out the most in the past, and it's the only medication the patient would agree to take. He also had Diazepam and Haloperidol PRN. They were constantly used, but the patient refused to take anything else regularly.

After a few days, the hallucinations got better, but the patient became increasingly aggressive and delusional. Threatening other patients and even physically assaulting one. He has a past history of physical violence. A judge approved that we may withhold him for 4 weeks, and we can isolate him and restrain him when needed for the next week. But up until now he continues doing it in a "voluntary" basis.

He agreed with us on the need to escalate the medication and takes the medication voluntarily. Currently there is no legal basis to apply for involuntary medication.

This is a picture of where we are currently at with the medication. Diazepam and Haloperidol were switch from PRN to regular medication. Our attending added Zuclopenthixol and According to him, the plan is to switch from Cariprazine to Risperidone. And eventually reduce Haloperidol, Zuclopenthixol and Diazepam.

And here I am, with little to no experience with antipsychotics and polypharmacy. But the little that I know is telling me that 4 antipsychotics are a red flag. I just wanted some input and advice. Thanks!

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[michaelrack]

Probably 1 antipsychotic too many. Sounds like either haldol or zuclopenthixol needs to be stopped. Sorry, but your attending sucks, based on the information given

 

[clausewitz2]

If cariprazine is all he will take, is there any reason not to try a higher dose?

 

[comp1]

My general rule is one antipsychotic. If there's some bizarre reason you need to do two or are cross titration, at the very least look at the binding profiles to make sure they aren't just completely overlapping. I've certainly never heard of Zuclopenthixol, but it looks like a typical used in the UK and Australia? Cariprazine is a very new antipsychotic at least in the US. I'm hoping if your attending is switching from that to risperidone it's either for cost purposes or to get like a long acting paliperidone? Given that it seems like you aren't in the US, it's hard to tell what options you have.

 

[SeniorWrangler]

I’ve seen long-time very refractory patients with psychotic disorders end up on multiple meds because it somehow seems to work better than anything else, but this is clearly not the case here.I’d be concerned about causing a painful dystonia that puts him off meds entirely.

 

[clozareal]

4 is probably too much but that guidance is from data on schizophrenia where patients are compared to placebo and are much less treatment resistant. You won't be getting those in state hospitals to be in these studies. Much of it is clinical lore rather than evidence-based medicine, although there is data on using augmenting agents with clozapine, such as risperidone and aripiprazole. Your patient probably needs a clozapine trial. Often times adherence gets better once stabilized on clozapine.

Perhaps since you're a resident, you can bring up this patient and this journal article that was recently published on antipsychotic polypharmacy to a journal club? Antipsychotic polypharmacy is probably more common than we think and there is an argument for it.

Safety of Antipsychotic Polypharmacy Versus Monotherapy in a Nationwide Cohort of 61,889 Patients With Schizophrenia | American Journal of Psychiatry

Objectives: The authors sought to study the safety of antipsychotic polypharmacy compared with monotherapy in specific dosage categories. Methods: Patients with schizophrenia (N=61,889; median follow-up, 14.8 years [IQR=7.4–22.0]) were identified from the Finnish nationwide inpatient care...

ajp.psychiatryonline.org

Abstract​

Objectives:​

The authors sought to study the safety of antipsychotic polypharmacy compared with monotherapy in specific dosage categories.

Methods:​

Patients with schizophrenia (N=61,889; median follow-up, 14.8 years [IQR=7.4–22.0]) were identified from the Finnish nationwide inpatient care register and followed up over the period 1996–2017. Antipsychotic polypharmacy was compared with monotherapy in seven dosage categories (<0.4, 0.4–<0.6, 0.6–<0.9, 0.9–<1.1, 1.1–<1.4, 1.4–<1.6, and ≥1.6 defined daily doses [DDDs] per day) in terms of risk of severe physical morbidity, indicated by nonpsychiatric and cardiovascular hospitalizations (adjusted hazard ratio). Within-individual analysis was used in an effort to eliminate selection bias.

Results:​

The mean age of the cohort was 46.7 years (SD=16.0), and 50.3% (N=31,104) were men. Among patients who had used both monotherapy and polypharmacy, the risk of nonpsychiatric hospitalization was significantly lower during polypharmacy use at all total dosage categories above 1.1 DDDs/day with differences up to −13% than during monotherapy use of the same dosage category (for 1.1–<1.4 DDDs/day, adjusted hazard ratio=0.91, 95% CI=0.87–0.95; for 1.4–<1.6 DDDs/day, adjusted hazard ratio=0.91, 95% CI=0.86–0.96; and for ≥1.6 DDDs/day, adjusted hazard ratio=0.87, 95% CI=0.84–0.89). The risk of cardiovascular hospitalization was significantly lower for polypharmacy at the highest total dosage category (−18%, adjusted hazard ratio=0.82, 95% CI=0.72–0.94). The results from the comparisons between monotherapy and no use and between polypharmacy and no use were in line with the primary comparison of polypharmacy and monotherapy within the same individual. Comparison of any polypharmacy use with any monotherapy use showed no significant difference for nonpsychiatric or cardiovascular hospitalization.

Conclusions:​

The results show that antipsychotic monotherapy is not associated with a lower risk of hospitalization for severe physical health problems when compared with antipsychotic polypharmacy. Treatment guidelines should not encourage use of monotherapy instead of antipsychotic polypharmacy without any existing evidence on the safety issues.

 

[ObsequiousAplomb]

It sounds like the attending is already trying to break down the polypharmacy. They even said they're trying to get the patient down to just Risperdal. They're trying to sedate this person while they're severely agitated. Giving Haldol IM 6 times a day isn't any more effective than 3 times a day at that. It makes sense to be throwing in a few other tranquilizers.

Obviously, since you're in Europe you have different meds than us. As others have stated, generally yeah we do one antipsychotic at a time for the treatment of schizophrenia (and we give additional tranquilizers when people are acutely agitated like your patient). Clozapine certainly looks like a good option given the vignette, and so would a long-acting injectable like a Risperdal or it's baby brother Invega. If you're going to do an LAI + clozapine I'd recommend it either be a Risperdal or an Abilify formulation.

Your attending's polypharm with antipsychotics is usually a symptom of severely agitated patients and a clinical setting that shuns away from benzodiazepines. Personally, I'd aggressively treat this person's agitation with Valium 10 or 20 BID or TID PO for 2-3 days before coming down (no benzo after day 3-6 ideally) in addition to an antipsychotic. 2 / 5 / 2 / 5 are the doses you gave of Valium. That's nothing. 5 mg is like a beer. You gave that person the equivalent of 2.5 beers in a day to chill out. Try harder. The haldol is only 5. That's fine, but obviously not a megadose. The doses of zuclopenthixol are on the higher end if that's just one day we're looking at as 100 mg is generally the ceiling for it. That's also only 1 mg of Risperdal.

Could probably get the same effect with Risperdal 3 BID or something. What we're looking at is low doses of 3 antipsychotics and a robust dose of one. that's kind of silly, but the attending is consolidating it all, as they said.

 

[Stagg737]

Imo, list above is not ideal but not outrageous either considering final plan seems to be to cross-titrate to a 2 antipsychotic regimen. I prefer 1 scheduled antipsychotic if possible, but there is certainly data suggesting 2 can be necessary and I've encountered plenty of patients who required 2 in order to be remain stable. If 2 or more antipsychotics are required and barely working I agree clozapine should absolutely be in the discussion as well. My understanding of OP's situation:

Cariprazine was scheduled but not effective alone. Zulcopenthixol (I know nothing about this med) was added to control symptoms. Sounds potentially reasonable. Haldol + diazepam was PRN but was changed to scheduled. Obviously not ideal, but if it was Q6H PRN and patient was requiring TID doses for days it may as well just be scheduled. Again, not ideal but we sometimes have to do this on the medical floors when patients are severely agitated and assaulting people. These are typically the patients that had been on a precedex drip or intubated and we're trying to avoid re-intubating. Adding risperidone as a cross-titration is not ideal, but if you're actively cross-titrating I can see the reasoning. I'm not sure why the zulcopenthixol was added, but seems like with the right timeline I could see how the doc got there.

After a few days, the hallucinations got better, but the patient became increasingly aggressive and delusional. Threatening other patients and even physically assaulting one. He has a past history of physical violence.

Currently there is no legal basis to apply for involuntary medication.

Idk if this is another cultural difference like what you had posted in the thread about the substance unit, but I don't understand how there's no legal basis for involuntary medications for a patient who is actively assaulting people on the unit with a h/o physical violence. If he suddenly refuses all meds for 2-3 days how long would it take to get involuntary administration approved and how much damage could he do in that time? I'm all for patient autonomy, but this is baffling to me.

 

[comp1]

My reading of the vignette was that the patient was actually taking (most) medications prescribed and thus there was no reason to request involuntary medications outside of single emergent administrations. I'm guessing even in the most progressive of European countries you can still involuntarily medicate someone assaulting people. That said, I love learning about involuntary treatment laws in other states, so I'd certainly love hearing about them from another country.

 

[Stagg737]

My reading of the vignette was that the patient was actually taking (most) medications prescribed and thus there was no reason to request involuntary medications outside of emergent administration. I'm guessing even in the most progressive of European countries you can still involuntarily medicate someone assaulting people. That said, I love learning about involuntary treatment laws in other states, so I'd certainly love hearing about them from another country.

Fair. In my state involuntary administration of meds while inpatient is included once a court deems involuntary admission necessary, they are not separate hearings/statutes. In this case though I'd probably seek the right to force meds if the patient were this aggressive even if they were agreeable just to make sure it is covered if necessary. Not saying I would force meds, but being able to do so immediately if necessary can make a huge difference.

 

[Candidate2017]

Here is one of my current patients, with whom I'm having problems understanding how to proceed. As, I have the feeling, that we are managing him incorrectly.

Don't be that stereotypical psychiatrist. The one who knows better. The covert narcissist who loves to judge without seeing all the facts. Psychiatry attracts lots of those. We give nurses a run for their money in terms of loving to tear each other down.

The medication list is a work in progress. Don't worry too much about something that is not yet a finished product.

But here is the reality in which we operate:

Patient's mind broke. We can fix broke mind. But society deems that a person with a broken mind is fit to pick and choose their treatment. This is like letting an intubated patient in the ICU deliriously pick and choose which pressors you can use. Or waking an anesthetized surgery patient every now and then to get their input on where you should cut, what tools you should use, how you should suture. You end up with something that looks like Frankenstein's monster, but with entrails hanging out.

So yeah, the finished medication list will likely look just as bad. But we'll go ahead and blame the clown show on the doctors.

 

[whopper]

Caripiprazine doesn't act as an antipsychotic at 1.5 mg daily in most cases. You need to get it to at least 3mg+, more being better in most patients.
If you want to understand antipsychotics as a real physician I'd recommend you start with reading CATIE trial and go from there. These days CATIE is behind the times, but it's the fastest way from 1 source to get up to speed.

Don't be that stereotypical psychiatrist. The one who knows better. The covert narcissist who loves to judge without seeing all the facts. Psychiatry attracts lots of those.

I'd say medicine in general attracts this type of personality, just that psychiatrists if they don't know what they're talking about could resort to psychobabble as a defense.
Patient: Why haven't I gotten better?
Bad Psychiatrist: What is better? What is the sound of one hand clapping? Maybe it's your mother.

 

[comp1]

I do wish all states (and countries) granted involuntary medication with involuntary detention automatically, but I think it's unfortunately pretty rare.

 

[jbomba]

My general rule is one antipsychotic. If there's some bizarre reason you need to do two or are cross titration, at the very least look at the binding profiles to make sure they aren't just completely overlapping. I've certainly never heard of Zuclopenthixol, but it looks like a typical used in the UK and Australia? Cariprazine is a very new antipsychotic at least in the US. I'm hoping if your attending is switching from that to risperidone it's either for cost purposes or to get like a long acting paliperidone? Given that it seems like you aren't in the US, it's hard to tell what options you have.

In correctional or state hospital settings it's not uncommon to see dual antipsychotics. Clozapine and ability or latuda have some decent evidence of efficacy.

 

[whopper]

Mentioned this before, but since there's some people wanting to learn, there's only a one antipsychotic regimen that consistently beats Clozapine by itself or Clozapine with just any other antipsychotic in studies.

That's Clozapine + Amisulparide.

If you ever get a patient in need of such a combo, Amisulparide isn't available in America.

Also data from the AJP showed 2 antipsychotics showed better efficacy vs 1. The obvious problem being more noncompliance, side effects, inconvenience, and expense.

I do wish all states (and countries) granted involuntary medication with involuntary detention automatically, but I think it's unfortunately pretty rare.

I used to run a long-term forensic unit where most patients refused meds. Anyone meeting hold criteria and refused meds-you did the involuntary med request immediately, put in all of the meds, not just 1-2, ALL OF THEM. Anyone putting in 1 or 2 and it didn't work then needing to wait another few weeks to do another court request would be called into the CCO's office and given a lesson that should've been taught in residency, told they've wasted tens of thousand of dollars of the hospital's money, the patient's time, well being, and told to how to do it the right way.

 

[annoyedpsychiatrist]

For most patients I think one antipsychotic at the correct dose is the way to go, but there are some very very sick patients, who arent clozapine eligible for various reasons, where sometimes i may use two antipsychotics. I have seen some people benefit from two antipsychotics

The hard part is, in my last job people would come in on 4-5 antipsychotics and you didnt know which ones they were actually compliant with, when they were started, what actually helped the pt, etc.

 

[FlowRate]

The very seasoned CMHC docs who taught our 3rd year didactics were always fond of two things: Ensure you fully optimize the dose, sometimes you need truly atypically high doses of some medications. If that fails, start another medication slowly, watch for tolerance, and, if the patient gets better, it's more likely to be thanks to the second medication rather than the combination of the two. Very slowly taper the first to test that hypothesis. This was advice for treatment patients with really severe persistent psychosis who were just stable enough to be outpatient but still very symptomatic.

The other thing I saw a couple of times in residency were patients who were stable on one antipsychotic, but needed two to stabilize. One particular patient, who would be stable on just olanzapine, but needed haloperidol to stabilize while inpatient (leaving her on just olanzapine did nothing if she was acutely decompensated.) Why did she keep destabilizing, you ask? Because her group home kept screwing up administration of her one antipsychotic.

 

[Candidate2017]

For most patients I think one antipsychotic at the correct dose is the way to go, but there are some very very sick patients, who arent clozapine eligible for various reasons, where sometimes i may use two antipsychotics. I have seen some people benefit from two antipsychotics

From what I see, it's a spectrum.

One antipsychotic at low to moderate dose = borderline or other unspecified or first break
One antipsychotic at max dose = now we're starting to cook
.
.
.
Two antipsychotics at supratherapeutic doses = yeah, you're def schizophrenic

 

[annoyedpsychiatrist]

From what I see, it's a spectrum.

One antipsychotic at low to moderate dose = borderline or other unspecified or first break
One antipsychotic at max dose = now we're starting to cook
.
.
.
Two antipsychotics at supratherapeutic doses = yeah, you're def schizophrenic

yea sometimes, you basically dont have many options in the community health setting.