Should we be using the "new three" neuroleptics?

[393656]

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As we are seeing the second and a half generation anti-psychotics come out over the past few years: iloperidone, lurisadone and asenapine, I am wondering who is using these?

Cost is surely key and I am guessing they are not typically covered by insurance.

However the dilemma I have been thinking about is regarding the outpatient treatment of patients and whether it is more appropriate at this point to use these 3 (abilify and geodon as well) due to signifigantly less metabolic effects? I personally have no experience in treating severe psychosis or schizophrenia with them and I am not sure if people feel they are effective but assuming they are for this arguement. I have used them in bipolar, ocd and MDD augmentation patients.

Is it really the best for the patient to use risperdaly, seroquel, zyprexa any more? Especially since they will go generic first, when there are alternatives that do not put them at nearly as high of a risk for metabolic risks, do we owe it to patients and will this/should this be the standard of care?

The new 3 actually all really are kind of a pain as far as delivery. Iloperidone is BID dosing and more orthostasis than risperdal, asenapine is BID dosing AND sublingual with no food/water for 10minutes after (which I could see people not sticking to this as they like to wash the taste out), and lurasidone needs >350 calories similar to geodon. Not saying these are deal breakers but sure do not help ease of use for generally poorly compliant patients.

Given that they have such an improved metabolic/weight profile however are we obligated to atleast try and use these three, abilify or geodon before ever venturing into the risperdal/seroquel/zyprexa world? I personally love seroquel so I do not see myself doing this necessarily anytime soon but the thought has crossed my mind

 

[whopper]

When factoring in what medication to use, you're going to have to figure in the patient's profile, among several other factors such as efficacy, price, side effects, likelihood the patient will stay on the treatment regimen, among other factors.

That said, since the latest antipsychotics don't have a CATIE type study done on them so far, and I haven't given them much, I'm still curious as to how they will fit into the big scheme.

In my own approach, I'm not trying the latest meds (Fanapt, Lutada, Saphris) unless the others don't work. Why? All very new meds are on FDA Clinical phase 4 testing. Pretty much any brand new medication still has not been tested on thousands of people or more. When a med is given out to the public, often times there's a side effect not known to occur that is only discovered after it's given to thousands to millions of people but it was not detected in the initial testing on people that is often around the hundreds at best.

I figure in a few years time, more data will come out, and I'm not completely against giving out the newest meds. I still haven't been able to get enough data as to what specific makes these meds significantly different in terms of what their effects are to factor them into my mental algorithm.

Geodon was in CATIE, so as long as you read CATIE, IMHO, you should be able to factor it into your own practice recommendations. Abilify's been out for some time, there's now much more data then when it came out, and while there's been no CATIE type study on it, I've given it out enough to the point where I feel I have a good grasp of what to anticipate with it.

I personally love seroquel

While in residency, I noticed the residents having a favorite medication. I think this is a natural process of the learning curve. You got a patient, you tried a medication, you give it out, it works, and now you like it.

I would, however, recommend that you strive to go a bit further with time.

I'm going to compare this to a restaurant. One goes to a restaurant, one likes it, and now one doesn't want to try another one. Once you've been to several, you know that tastes change, and different restaurants complement specific situations better.

From my own experience, unless the patient had problems sleeping, most patients I've known did not prefer Seroquel when they were tried on other medications. Indeed, in CATIE it was the medication that was STOPPED THE MOST over the shortest period of time by patients in that study, highly suggesting lower efficacy and patients not finding the benefit/risk ratio worth it.

Based on the data in studies, I definitely think it has a place in my own algorithm...patients that have severe problems sleeping, in need of weight gain, non-drug using, prone to EPS, TD, or have other movement related issues such as Parkinson's disease, bipolar depression, or anxiety combined with bipolar disorder or a psychotic disorder (norquietapine per Henry Nasrallah is an SNRI, though I haven't seen a study backing this, but I know Nasrallah doesn't say it unless there's a study backing it). But the above has to be taken in the context that each patient is different, and that others such as Zyprexa could also be used in many of the above cases as well.

Ultimately, what med should be tried is the one best for the patient, and unfortunately, we truly will never know what that med is until several have been tried, but by factoring in the patient's profile with that of the medication, mixed in with what you've seen over the course of years, one can make the best educated guess. That guess should be based on the scientific data tempered with what you see from personal experience with the medication. When you've reached that point, IMHO, most people will no longer have a "favorite" medication.

For that reason, once you've been comfortable with one antipsychotic, I recommend you not settle on it. Continue to try others based on the data you see in journals. After all, most of you here are in residency, when else will you learn this?

Please do not become one of those doctors I see that gives out one med for every single thing...e.g. an attending that ticked me off in residency "I gavie Zyprexa and Paxil to all my patients"....literally.

 

[393656]

Great analogy whopper. I agree and strive to practic evidence based medicine but you just cannot help to have a few favorites usually based on nothing more than subjective good experiences. I never let it trump the clinical evidence however and only use those favorites if it is between my favorite and another medication with equal indication for what I am treating.

Are you in cinnci? I am at OSU and we get many lectures from nasarellah so I am generally a big fan. I agree that is said often about norquetiapine and I believe it, however I really do not buy that is why its effective for depression. Its no different than adding in cymbalta or nortriptyline which clear are not as effective as far as I know. I believe it has a mechanism that we just do not understand and using the NRI mechanism is just another way to categorize it neatly into a reason why it "works" for depression more so than other aytpicals based on the studies anyway.

I agree with the new 3 being new and not having any big studies, however at this point if you are pumping out a drug with the same mechanism as all the aypticals minus the histamine and anti-cholinergic and 5ht2C antagonism which all cause a bunch of metabolic problems, I am not as concerned about needing a big study I guess. They are not new mechanisms that are competing with current tried and true treatment.

For now I am not using them and see no reason as I could use geodon and abilify (even abilify is not panning out to be as benign as most thought as far as weight and lipids). Perhaps down the line though if patients are not tolerating geodon tese will be in my repetoir.

 

[whopper]

Yeah, well I too had a "favorite" med while in residency, but when I read CATIE for the first time, I thought to myself....WTF? I shouldn't be having a favorite med.

I felt CATIE was a rosetta stone in terms of understanding the antipsychotics to the degree where we had good and real data on what truly separated one from another.

I talked to Doug Lehrer, a researcher doing work with the NIMH, and I asked him if they were going to do another CATIE trial, but this time using the atypicals not used in the original studies. He told me, unfortunately, no. Although he did not do any CATIE work as far as I know, I figured he had enough connections in NIMH to at least possibly know if one was in the works. He agreed he thought it was a great idea, but he also mentioned that the way the political and budget forces were working, he did not see this happening. Someone could of course do this type of study outside of the NIMH, but they'd have to be at a big research place to use the types of numbers of subjects to have the numbers CATIE generated. If I had the research clout, I would like to try but I'm not doing any real empirical research at this time, and all the projects I could see myself doing in the next year or two are mostly just in forensic psychiatry.

I haven't yet seen if NEI (Stephen Stahl) has done any extensive articles on the new meds. I'd be curious to see if he did.

 

[393656]

I think we are looking at about 10 years from now for the next epic study in schizophrenia pharmacoptherapy. It will be after the NMDA agonist drugs come out and ultimately will be a comparison of neuroleptics v nmda v combination. Atleast that is my prediction

PS-anyone heard of the closes nmda drug coming to market? severeal in phase 2 and 3 but have not heard anything coming to market

 

[TexasPhysician]

I've used Saphris in patients that have previously been on everything else. The other two I have yet to touch.

 

[medium rare]

I've used Saphris in patients that have previously been on everything else. The other two I have yet to touch.

I've used Saphris with about a dozen patients so far and have had encouraging results, minus the excessively bad taste it leaves - even with the Black Cherry flavor.

 

[firedoor]

Given that they have such an improved metabolic/weight profile however are we obligated to atleast try and use these three, abilify or geodon before ever venturing into the risperdal/seroquel/zyprexa world?

So long as they have comparable effectivenesses, I believe that patients generally deserve trials of medications with lesser propensities for serious side effects (e.g. metabolically) before trying those with greater such propensities, especially when the medication is likely to be given on a long-term basis. I wouldn't want to start my mother on Zyprexa as a first-line antipsychotic, yet such practice happens all the time. I wish this were not the case, especially since antipsychotics are handed out like candy these days, often exposing patients to a highly questionable cost/benefit ratio IMHO.