Opinions on stopping zyprexa

[Attending1985]

I have a schizophrenic patient who was on saphris doing ok but not great. He stopped it became very psychotic and was started on Invega inpatient. He was still psychotic after initial 156 mg dosage and it was upped to 234 the next dosage. A week after that dosage (because he was still psychotic) Zyprexa 5 mg was added. He then improved. He’s been on the invega 234 plus 5 of zyprexa for a few months and is doing well. He wants to taper the Zyprexa to be on monotherapy. I’m nervous about tapering it based on history. Any opinions on risk level of tapering the Zyprexa?

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[Dr. ADT]

Is he having any side effects from Zyprexa? I would keep it as long as he is stable especially that the 5 mg is a low dose.

 

[ObsequiousAplomb]

Adding Zyprexa one week after an Invega injection dose increase may have been somewhat premature. Given the information provided, it isn't clear whether it was:
A) more time taking Invega
B) the increased Invega dose
C) the addition of Zyprexa

that resulted in stability.

That being said, there are known risks to polypharmacy. There are known risks to decompensation. Decompensation might not be fully addressed by resuming the previous regimen. After a discussion of the risks, I usually leave this mostly up to the patient.

If I were to discontinue the Zyprexa, I would write a 30-day refill for it and instruct the patient to stop if they would like, but to keep the bottle of Zyprexa nearby in case they start to feel off so they can restart it before the next appointment. Closer follow-up and all that jazz.

 

[Merovinge]

Adding Zyprexa one week after an Invega injection dose increase may have been somewhat premature. Given the information provided, it isn't clear whether it was:
A) more time taking Invega
B) the increased Invega dose
C) the addition of Zyprexa

that resulted in stability.

That being said, there are known risks to polypharmacy. There are known risks to decompensation. Decompensation might not be fully addressed by resuming the previous regimen. After a discussion of the risks, I usually leave this mostly up to the patient.

If I were to discontinue the Zyprexa, I would write a 30-day refill for it and instruct the patient to stop if they would like, but to keep the bottle of Zyprexa nearby in case they start to feel off so they can restart it before the next appointment. Closer follow-up and all that jazz.

All of this and just do it slowly, can go to 2.5 for several weeks or a even a month+ and see how the patient does and adjust from there. If there is no worsening of sx at 2.5, you can feel better about going off.

 

[forchinet121]

Ideally it could make sense to keep him on both for at least 6 months before starting to taper just to be safe but there’s no “correct” way of doing it, also it’s up to the patient if he’s not gonna take it then he’ll just stop himself and all this talk becomes moot

 

[clozareal]

You're not going from an antipsychotic to nothing like he did in the past. Rebound psychosis and withdrawal/discontinuation syndromes have been well documented in the literature. He has the baseline of the Invega to help him with this from going off of the olanzapine, but I agree with Merovinge in going down to 2.5mg first for several months, then maybe even 1.25mg if you are really worried. That last bit is the toughest to come off and associated with the most side effects.

You need to make sure he keeps getting regular intervals of Invega though and sometimes you need to even get it more frequently than q28days if he starts exhibiting worsening psychotic symptoms at day 24-28, which I've seen.

 

[Stagg737]

Agree with the above, if he was just started on the two leave it for a few months then drop to a 2.5mg dose for a couple of months before stopping. Tell him if he feels like he's decompensating with only 2.5mg to go back to 5mg and call you. Having a PRN dose of risperidone/paliperidone for the last week before the next injection also isn't a bad idea until you're sure Q28days is adequate. I've seen plenty of patients get Invega Q3weeks because of return of symptoms in week 4.

 

[Evidence Based]

Our pharmacist always tells us that LAIs can take months to reach steady state- the half life for Sustenna is like 25 days, and for any drug you need 3-4 half lives to reach steady state. Did this person receive a loading dose (234), then 156, and then 234 again? Or did he not even get a loading dose inpatient? If he really just got two injections (1x 156 and 1x 234) then he was nowhere close to steady state at the higher dose. Even if he had been loaded inpatient I would expect a few months to really see the effect of 234 every 28 days.
The most conservative option is a slow taper as people have discussed, but I really suspect the patient's recovery is due to more time at a therapeutic dose of paliperidone and not the low dose of olanzapine. Shared decision making is always the way to go here of course.

 

[ObsequiousAplomb]

Our pharmacist always tells us that LAIs can take months to reach steady state- the half life for Sustenna is like 25 days, and for any drug you need 3-4 half lives to reach steady state. Did this person receive a loading dose (234), then 156, and then 234 again? Or did he not even get a loading dose inpatient? If he really just got two injections (1x 156 and 1x 234) then he was nowhere close to steady state at the higher dose. Even if he had been loaded inpatient I would expect a few months to really see the effect of 234 every 28 days.
The most conservative option is a slow taper as people have discussed, but I really suspect the patient's recovery is due to more time at a therapeutic dose of paliperidone and not the low dose of olanzapine. Shared decision making is always the way to go here of course.

Oh wow, I hadn't even noticed he said "after the first 156" so really he's nowhere near steady state, and it may even be questionable whether he needs the full 234 every month this early in the recovery.

 

[Candidate2017]

What exactly do you mean when you say he was "still psychotic" after a week of Invega (or a week post-Invega increase)? As pointed out, it takes a while to reap the full benefits of an antipsychotic. At least 2-4 weeks. So yes, he should still have some psychosis unless your intent is to completely zombify him, which is valid in cases of danger (or if you are an old school Top Gun psychiatrist who believes in carpet bombing dopamine receptors until EPS happens to find the danger zone, and then pull back the dose).

The question is to what degree of psychosis was he experiencing. Was he on the verge of following command AVH to hurt himself or others, unable to distinguish AVH from reality, etc? Or was he merely complaining of residual voices while the Invega was just starting to kick in? If it's the latter case, then watchful waiting and encouraging distress tolerance at the current dose may be useful.

Also, was there Invega oral overlap? The manufacturer says none required. Which is ok, as long as you and the patient can tolerate the residual psychosis while the LAI kicks in.

As for Zyprexa 5 mg, I'd rip the Band Aid off. He can self-monitor and hold on to a bottle as a transitional object, if it makes everyone feel better. I wouldn't even consider Zyprexa 2.5 mg, which is the equivalent of throwing a ping pong ball at a charging borderline buffalo.

 

[forchinet121]

What exactly do you mean when you say he was "still psychotic" after a week of Invega (or a week post-Invega increase)? As pointed out, it takes a while to reap the full benefits of an antipsychotic. At least 2-4 weeks. So yes, he should still have some psychosis unless your intent is to completely zombify him, which is valid in cases of danger (or if you are an old school Top Gun psychiatrist who believes in carpet bombing dopamine receptors until EPS happens to find the danger zone, and then pull back the dose).

The question is to what degree of psychosis was he experiencing. Was he on the verge of following command AVH to hurt himself or others, unable to distinguish AVH from reality, etc? Or was he merely complaining of residual voices while the Invega was just starting to kick in? If it's the latter case, then watchful waiting and encouraging distress tolerance at the current dose may be useful.

Also, was there Invega oral overlap? The manufacturer says none required. Which is ok, as long as you and the patient can tolerate the residual psychosis while the LAI kicks in.

As for Zyprexa 5 mg, I'd rip the Band Aid off. He can self-monitor and hold on to a bottle as a transitional object, if it makes everyone feel better. I wouldn't even consider Zyprexa 2.5 mg, which is the equivalent of throwing a ping pong ball at a charging borderline buffalo.

The difference between 5 mg and 2.5 mg is actually significant and the difference between 2.5 and 0 is even more significant when considering dopamine receptor occupancy so I wouldn’t go from 5 to 0 although this does seem to be standard

 

[clozareal]

It takes MONTHS to reap the benefits of oral antipsychotics and even then, you can reasonably expect about a 30% reduction in symptoms. The latest research I saw on the plateau of symptom improvement was around 12 weeks. Those who have complete remission of psychotic symptoms are uncommon (Stahl says 15% but I can't find his citation for this).

 

[allantois]

Maybe even have him reduce by a quarter at a time

 

[clausewitz2]

It takes MONTHS to reap the benefits of oral antipsychotics and even then, you can reasonably expect about a 30% reduction in symptoms. The latest research I saw on the plateau of symptom improvement was around 12 weeks. Those who have complete remission of psychotic symptoms are uncommon (Stahl says 15% but I can't find his citation for this).

Really? Sherwood et al 2006 says 6 weeks is when the treatment effects plateau, but of course I am open to new research. Do you remember where you got the 12 week figure?

I agree about complete remission being unusual. This is why acceptance based therapeutic approaches can be very helpful with this population. 'I hear voices but they are irrelevant to what i choose to do' is an ideal end goal.

 

[Candidate2017]

The difference between 5 mg and 2.5 mg is actually significant and the difference between 2.5 and 0 is even more significant when considering dopamine receptor occupancy so I wouldn’t go from 5 to 0 although this does seem to be standard

Significant receptor occupancy or not, I've never seen Zyprexa 5 mg or 2.5 mg do much for a schizophrenic. It may as well be Zyprexa 0 mg, which is why psychiatrists don't have a problem taking Zyprexa 5 mg straight down to 0 mg.

Zyprexa 5 mg, in my opinion, helps slightly agitated people who want to be slightly less agitated, slightly less agitated.

 

[ObsequiousAplomb]

Zyprexa 5 mg can certainly be a therapeutic dose for many people living with schizophrenia. Most providers and patients never find out because the dose was increased before the medication had time to be effective and improvement was attributed to the higher dose instead of the cumulative exposure.

Zyprexa 10 mg can certainly be effective for some for whom 5 mg was ineffective. So can 20 mg. I've seen plenty of patients who went up to and sometimes past 60 mg and frankly I haven't seen much of a real difference compared to 5-20, aside from short-term benefits in sedation and nursing satisfaction.

Zyprexa 2x for the first few days-to-weeks followed by a reduction to x is also entirely effective for many people, given the propensity for levels to increase given its pharmacokinetic properties.

Also important to remember that Zyprexa 5 mg as part of polypharmacy is an entirely different animal than Zyprexa 5 mg monotherapy.

 

[deleted456421]

As someone who restarted an acutely ill patient on Invega after NMS on the same medication at a state hospital, I can attest to the fact it can take months for the medication to achieve full effectiveness. I also frequently see people aggressively titrated on various regimens while inpatient who tolerate drastically lower doses (or entirely different medications) without adverse effects.

 

[clausewitz2]

Zyprexa 5 mg can certainly be a therapeutic dose for many people living with schizophrenia. Most providers and patients never find out because the dose was increased before the medication had time to be effective and improvement was attributed to the higher dose instead of the cumulative exposure.

Zyprexa 10 mg can certainly be effective for some for whom 5 mg was ineffective. So can 20 mg. I've seen plenty of patients who went up to and sometimes past 60 mg and frankly I haven't seen much of a real difference compared to 5-20, aside from short-term benefits in sedation and nursing satisfaction.

Zyprexa 2x for the first few days-to-weeks followed by a reduction to x is also entirely effective for many people, given the propensity for levels to increase given its pharmacokinetic properties.

Also important to remember that Zyprexa 5 mg as part of polypharmacy is an entirely different animal than Zyprexa 5 mg monotherapy.

Work with FEP folks for any length of time and you will meet the walking olanzapine advertisements who are totally functional and going to college on 5 mg of Zyprexa and stop going to class and tell their parents about the people living in the walls monitoring them when they don't take it. I have seen similar cases with risperidone 0.5 mg BID, abilify 10 mg and 40 mg of lurasidone. The people who do really well with antipsychotics for actual psychosis are the people who don't end up in resident clinics or CMHCs.

 

[ObsequiousAplomb]

Work with FEP folks for any length of time and you will meet the walking olanzapine advertisements who are totally functional and going to college on 5 mg of Zyprexa and stop going to class and tell their parents about the people living in the walls monitoring them when they don't take it. I have seen similar cases with risperidone 0.5 mg BID, abilify 10 mg and 40 mg of lurasidone. The people who do really well with antipsychotics for actual psychosis are the people who don't end up in resident clinics or CMHCs.

Agreed.

I will add that based on all the clinical experience and literature I have seen, Abilify response and remission rates get WORSE when you go past 15 mg per day. Yet for some reason people love going to 30 or 45 and after 3-4 days say it is a terrible antipsychotic that never works.

 

[Desired Member]

...say it is a terrible antipsychotic that never works.

I feel called out

 

[Candidate2017]

Work with FEP folks for any length of time and you will meet the walking olanzapine advertisements who are totally functional and going to college on 5 mg of Zyprexa and stop going to class and tell their parents about the people living in the walls monitoring them when they don't take it. I have seen similar cases with risperidone 0.5 mg BID, abilify 10 mg and 40 mg of lurasidone. The people who do really well with antipsychotics for actual psychosis are the people who don't end up in resident clinics or CMHCs.

Aside from the ones I've seen commit suicide within 1-2 years of their diagnosis, college patients in first episode clinics do well mainly because of family support and self-selection. But they eventually gain independence, get less family supervision, feel better and invariably get a second, third, and fourth episode for which a sprinkle of antipsychotic no longer work.

 

[clausewitz2]

Aside from the ones I've seen commit suicide within 1-2 years of their diagnosis, college patients in first episode clinics do well mainly because of family support and self-selection. But they eventually gain independence, get less family supervision, feel better and invariably get a second, third, and fourth episode for which a sprinkle of antipsychotic no longer work.

I'd like to see the citations supporting this, the literature I am familiar with does not really suggest better outcomes with high v low/moderate doses of these agents. I am not going to pretend that this is the modal experience for people with psychosis but this is the trajectory of a sizable minority. I did refer to college above but I am not just thinking about high SES folks or with highly supportive/low EE families.

Discontinuing treatment definitely happens, but I don't think it's as inevitable as you seem to feel it is.

EDIT: Liu et al. 2021 followed up with a Taiwanese FEP cohort (83% non-affective psychosis) a decade later and found 18% of them were taking <50 mg chlorpromazine equivalents daily during maintenance. This was strongly correlated with good functioning. Another 20 odd % had never had more than 200 mg CPE daily and were in full-time employment/education. This is not a pipe dream.

 

[Evidence Based]

Aside from the ones I've seen commit suicide within 1-2 years of their diagnosis, college patients in first episode clinics do well mainly because of family support and self-selection. But they eventually gain independence, get less family supervision, feel better and invariably get a second, third, and fourth episode for which a sprinkle of antipsychotic no longer work.

Would agree with @clausewitz2 that while someone on 1mg risperidone forever is not the most common outcome, it's important to realize there's a ton of selection bias in the "chronic" patients who end up in our clinics.

Would also just add that there's literature on effective antipsychotic dosing for both acute psychosis and relapse prevention, and that the plateau is much lower for many commonly used drugs (ex. aripiprazole 10, maybe 15, haldol 7.5) than is commonly seen in practice.
Acute Tx: Dose-Response Meta-Analysis of Antipsychotic Drugs for Acute Schizophrenia - PubMed
Relapse prevention: Examination of Dosing of Antipsychotic Drugs for Relapse Prevention in Patients With Stable Schizophrenia: A Meta-analysis - PubMed

I realize we're getting far afield here so apologies

 

[Stagg737]

Significant receptor occupancy or not, I've never seen Zyprexa 5 mg or 2.5 mg do much for a schizophrenic. It may as well be Zyprexa 0 mg, which is why psychiatrists don't have a problem taking Zyprexa 5 mg straight down to 0 mg.

Zyprexa 5 mg, in my opinion, helps slightly agitated people who want to be slightly less agitated, slightly less agitated.

I agree that Olanzapine 5mg isn't going to be adequate for many patients we see who come through the inpatient unit, but it can certainly be therapeutic for some. It's also certainly not a negligible dose, there are plenty of people who get nearly snowed with just low doses like olanzapine 5mg.

I will add that based on all the clinical experience and literature I have seen, Abilify response and remission rates get WORSE when you go past 15 mg per day. Yet for some reason people love going to 30 or 45 and after 3-4 days say it is a terrible antipsychotic that never works.

Idk about the first part, I've seen plenty of people needing 20mg doses or the LAI equivalent to maintain stability. I've never heard of anyone going to 45mg of Abilify and agree that I see no reason to go above 30mg (or even up to 30mg most of the time).

EDIT: Liu et al. 2021 followed up with a Taiwanese FEP cohort (83% non-affective psychosis) a decade later and found 18% of them were taking <50 mg chlorpromazine equivalents daily during maintenance. This was strongly correlated with good functioning. Another 20 odd % had never had more than 200 mg CPE daily and were in full-time employment/education. This is not a pipe dream.

Can you link that study. Liu et al is probably the most generic search term possible, I get everything from COVID studies to emission control to a paper on Jupiter's magnetosphere, lol.

Would agree with @clausewitz2 that while someone on 1mg risperidone forever is not the most common outcome, it's important to realize there's a ton of selection bias in the "chronic" patients who end up in our clinics.

Would also just add that there's literature on effective antipsychotic dosing for both acute psychosis and relapse prevention, and that the plateau is much lower for many commonly used drugs (ex. aripiprazole 10, maybe 15, haldol 7.5) than is commonly seen in practice.
Acute Tx: Dose-Response Meta-Analysis of Antipsychotic Drugs for Acute Schizophrenia - PubMed
Relapse prevention: Dose-Response Meta-Analysis of Antipsychotic Drugs for Acute Schizophrenia - PubMed

I realize we're getting far afield here so apologies

I think those are the same link, were they supposed to be different?

 

[Evidence Based]

I think those are the same link, were they supposed to be different?

Yes sorry my mistake! I'll correct the original post, second article is here: Examination of Dosing of Antipsychotic Drugs for Relapse Prevention in Patients With Stable Schizophrenia: A Meta-analysis - PubMed