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2 hours ago, Arj72 said:

I think I'll take the Zyprexa tonight even if I don't hear back from my pdoc (I think he's on vacation.... he mentioned it but not sure of the dates),  Will deal with any ramifications after that if there are any (beg forgiveness vs ask permission).  My pdoc knows I'm pretty responsible with my meds.

I'm pretty sure your pdoc won't have any issue with taking Zyprexa with Vraylar, especially if they know you're responsible and trust you with your choices and decisions.

2 hours ago, Arj72 said:

The question still remains though, if I should continue to truck on with the Vraylar.

How long in total have you been on it now?

2 hours ago, Arj72 said:

Right now, I don't have the restlessness/anxiety that I had at 3 this morning but I certainly feel on edge, just like when I started the Vraylar.  I had a total of 1 day respite, and now this.  Can't they just make a diet Zyprexa lite? :D 

You may just be one of the unlucky people who gets unrelenting and unremitting anxiety from Vraylar for as long as they take it. I've heard to give Vraylar at least a month or longer to really decide how you feel with it. Side effects can come and go in the meantime, but if it's absolutely nonstop and causing you great discomfort, if it were me in your shoes, I'd probably move on to something else, but then again, I'm not really one to stick things through with a medication. I'm very quick to switch or give up on a med that could've probably worked had I made it through the side effects. (Then again, side effects never go away IME...)

SERIOUSLY?!! I'm looking forward to Caplyta's release. It has been FDA approved, they just need to release it to pharmacies and to the public. My insurance I know won't cover it without a letter from my doctor, and even then it will be iffy. But it looks very promising. I think right now it's only indicated for schizophrenia, but they're working on indications for bipolar mania, bipolar depression, major depressive adjunct, insomnia, and psychosis and agitation associated with dementia. It's supposed to be a pretty good drug. It's another dopamine partial agonist (at least a presynaptic dopamine autoreceptors, which decreases dopamine release as well as other effects; it's an antagonist at postsynaptic receptors I believe), but it has super ultra potent 5-HT2A antagonism, and "built in" moderate SSRI properties.

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About 17 days now.

Quote

You may just be one of the unlucky people who gets unrelenting and unremitting anxiety from Vraylar for as long as they take it. I've heard to give Vraylar at least a month or longer to really decide how you feel with it. Side effects can come and go in the meantime, but if it's absolutely nonstop and causing you great discomfort, if it were me in your shoes, I'd probably move on to something else, but then again, I'm not really one to stick things through with a medication. I'm very quick to switch or give up on a med that could've probably worked had I made it through the side effects. (Then again, side effects never go away IME...)

SERIOUSLY?!! I'm looking forward to Caplyta's release. It has been FDA approved, they just need to release it to pharmacies and to the public. My insurance I know won't cover it without a letter from my doctor, and even then it will be iffy. But it looks very promising. I think right now it's only indicated for schizophrenia, but they're working on indications for bipolar mania, bipolar depression, major depressive adjunct, insomnia, and psychosis and agitation associated with dementia. It's supposed to be a pretty good drug. It's another dopamine partial agonist (at least a presynaptic dopamine autoreceptors, which decreases dopamine release as well as other effects; it's an antagonist at postsynaptic receptors I believe), but it has super ultra potent 5-HT2A antagonism, and "built in" moderate SSRI properties.

I'm about ready to throw in the towel myself.  I called my pdoc's answering service and found out he doesn't go on vacation until Wednesday.  Put in a message to hopefully see him before he leaves.  Taking the Zyprexa tonight.  Wish me luck.

BTW, how do you multiquote like that?

Edited by Arj72

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2 hours ago, Arj72 said:

I'm about ready to throw in the towel myself.  I called my pdoc's answering service and found out he doesn't go on vacation until Wednesday.  Put in a message to hopefully see him before he leaves.  Taking the Zyprexa tonight.  Wish me luck.

Well, that's unfortunate it didn't work for ya, I hope you can find something that does work, and that your pdoc gets back to you before he goes on vacation.

2 hours ago, Arj72 said:

BTW, how do you multiquote like that?

Select the text you want to quote with the mouse, and when you let go of the left mouse button, a button will pop up near the selected text that says "quote," and when you click it, it only quotes what you selected. I assume that's what you were asking about. 🙂 

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12 minutes ago, mikl_pls said:

Select the text you want to quote with the mouse, and when you let go of the left mouse button, a button will pop up near the selected text that says "quote," and when you click it, it only quotes what you selected. I assume that's what you were asking about. 🙂 

Cool

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I tried Vraylar myself. Lasted 4-6 weeks on 1.5mg and gave up. Went back to Rexulti, which is what I was taking before. Still taking it and prefer it to Abilify or Vraylar which are the only other two dopamine partial agonists. It's much more calming to me then either of the others. I know some people also have anxiety on Rexulti, but also keep in mind that I usually take 0.5mg or less. Currently taking 0.25mg. It really is just a sleep med and antidepressant for me at this dose and doesn't have much of its own anti-manic effect.

With Vraylar, I ultimately found it to be too stimulating. I've always responded best to the -pine antipsychotics and had a terrible experience with Abilify. So my experience with Vraylar is not all that surprising. But apparently it isn't all that surprising that many people who quit Abilify because of tolerability problems end up tolerating Rexulti just fine.

On 2/10/2020 at 5:01 PM, Arj72 said:

BTW, how do you multiquote like that?

If you're looking to quote multiple, unique posts, instead of clicking the quote link on one person's post, click the + sign next to the word Quote on each post you want to quote, then select the Quote button that should have appeared in the lower, right-hand corner of the page. It will take you to the Compose box where it has deposited the multiple quote boxes like the single quote function.

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11 hours ago, browri said:

If you're looking to quote multiple, unique posts, instead of clicking the quote link on one person's post, click the + sign next to the word Quote on each post you want to quote, then select the Quote button that should have appeared in the lower, right-hand corner of the page. It will take you to the Compose box where it has deposited the multiple quote boxes like the single quote function.

Wow, I had no idea... lol. Derp. I learned another way to multi-quote tonight.

11 hours ago, browri said:

which are the only other two dopamine partial agonists

Caplyta hits pharmacies in March! Every time I type or write that, it looks so wrong, and no matter how many times I check the spelling, it still looks wrong... lol

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On 2/22/2020 at 12:28 AM, mikl_pls said:

Wow, I had no idea... lol. Derp. I learned another way to multi-quote tonight.

Caplyta hits pharmacies in March! Every time I type or write that, it looks so wrong, and no matter how many times I check the spelling, it still looks wrong... lol

Yeah I really don't understand the naming there but I'm sure there was an extensive amount of marketing budget already poured into developing that idiocracy of a name so let's not give them too hard a time lest they go and spend more money to change it.

Also, I'm not sure Caplyta will get put under partial agonists with Vraylar, Abilify, and Rexulti. It is a partial agonist at pre-synaptic short form dopamine type 2 receptors, but it is still a pure antagonist at post-synaptic long form receptors. So in that regard it doesn't really belong neatly with other AAPs like Seroquel, Geodon, Zyprexa either. That is the one truly novel thing about lumateperone (Caplyta) is that we don't currently have a ligand for the dopamine type 2 receptor that can act as a partial agonist pre-synaptically and an antagonist post-synaptically.

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5 hours ago, browri said:

Yeah I really don't understand the naming there but I'm sure there was an extensive amount of marketing budget already poured into developing that idiocracy of a name so let's not give them too hard a time lest they go and spend more money to change it.

Also, I'm not sure Caplyta will get put under partial agonists with Vraylar, Abilify, and Rexulti. It is a partial agonist at pre-synaptic short form dopamine type 2 receptors, but it is still a pure antagonist at post-synaptic long form receptors. So in that regard it doesn't really belong neatly with other AAPs like Seroquel, Geodon, Zyprexa either. That is the one truly novel thing about lumateperone (Caplyta) is that we don't currently have a ligand for the dopamine type 2 receptor that can act as a partial agonist pre-synaptically and an antagonist post-synaptically.

Do you think most insurance companies would be in such a hurry to approve this for BPD treatment though?  I mean I can get most AAP's approved save for a preauth needed for on patent meds, but I worry that since Caplyta's only indication is schizophrenia, insurance won't cover it.

I'm interested in trying nonetheless.  Seems its side effect profile is better than the other AAP's.

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56 minutes ago, Arj72 said:

Do you think most insurance companies would be in such a hurry to approve this for BPD treatment though?  I mean I can get most AAP's approved save for a preauth needed for on patent meds, but I worry that since Caplyta's only indication is schizophrenia, insurance won't cover it.

I'm interested in trying nonetheless.  Seems its side effect profile is better than the other AAP's.

Well for anyone who has Prime Therapeutics as a pharmacy benefit manager, it looks like a lot of the state Blue's have updated the step therapy forms to include Caplyta. However at this point it isn't on my formulary. It does show up in the drug search though. That being said, they JUST added it to the ST form this month and it doesn't hit pharmacies until next month. So we might not know for a bit.

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18 hours ago, browri said:

Well for anyone who has Prime Therapeutics as a pharmacy benefit manager, it looks like a lot of the state Blue's have updated the step therapy forms to include Caplyta. However at this point it isn't on my formulary. It does show up in the drug search though. That being said, they JUST added it to the ST form this month and it doesn't hit pharmacies until next month. So we might not know for a bit.

Is caplyta going to be anything good or worth trying? Is it similar to any other med like similar to latuda or anything like that? Why is it only available in 42 mg capsules? It seems they are developing it for more than just schizophrenia indications if you read this news release. Thanks for any insights.
 

https://ir.intracellulartherapies.com/news-releases/news-release-details/fda-approves-intra-cellular-therapies-novel-antipsychotic

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12 minutes ago, Wonderful.Cheese said:

Is caplyta going to be anything good or worth trying?

Well it'll be worth trying in that there are things that are different about it relative to other antipsychotics. Dopamine antagonists usually behave as an antagonist at both pre-synaptic dopamine auto-receptors and post-synaptic receptors. This means that while post-synaptic antagonism dampens dopamine signaling, pre-synaptic antagonism increases dopamine release, and the increased dopamine release paired with post-synaptic blockade is theorized to be the state in which we experience movement disorders.

Caplyta will supposedly be different in its behavior depending on whether it binds to pre-synaptic dopamine receptors or post-synaptic receptors. Pre-synaptically, it will act as a partial agonist like Abilify, Vraylar, and Rexulti do. This will actually reduce dopamine release into the synapse. At the post-synaptic receptors, it will behave like the traditional silent antagonists like Seroquel, Risperdal, or even Haldol and Thorazine. However, pairing these two different actions may theoretically reduce the risk of prolactin elevation to 0 along with much significant impact on metabolic measures like glucose or triglycerides and cholesterol and a reduced risk for movement disorders. And by less risk, I mean that relative to Risperdal, as that was the active comparator they used in Caplyta trials to measure metabolic dysfunction.

Also, Caplyta is an absolute 5HT2A antagonist at even tiny doses (think 5-10mg). So at low doses it's great for sleep and boosting antidepressants. With increasing doses it directly inhibits the serotonin transporter like standard antidepressants and also blocks the dopamine receptors. So it's also one of a select few antipsychotics that can inhibit neurotransmitter transporters like antidepressants. Only other major examples I can think of are Seroquel inhibiting the norepinephrine transporter and Geodon, which has a modest effect on the SERT and the NET. In all these regards, it's different enough to at least try.

12 minutes ago, Wonderful.Cheese said:

Is it similar to any other med like similar to latuda or anything like that?

At the end of the day it will probably be more similar to the antagonists than the partial agonists. But no I don't think there is any way to directly compare Caplyta to any other existing atypical antipsychotic. Lumateperone is a member of a class of compounds called butyrophenones, of which the most notable is the typical antipsychotic, haloperidol (Haldol). However, melperone is an ATYPICAL antipsychotic of the same class that I believe may be used in other countries. In the U.S. there are no other FDA approved butyrophenone antipsychotics that I'm aware of except haloperidol, and that doesn't quite compare obviously seeing as haloperidol is a typical antipsychotic with far less appreciable effect on the serotonin system than atypical antipsychotics.

12 minutes ago, Wonderful.Cheese said:

Why is it only available in 42 mg capsules? It seems they are developing it for more than just schizophrenia indications if you read this news release. Thanks for any insights.

Psychosis and mania are measurable symptoms and much easier to get a drug approval for. The ability of an antipsychotic to reduce symptoms of psychosis in schizophrenia or mania in bipolar disorder is something that is outwardly apparent to clinicians, whereas treatment of affective/mood disorders typically requires more data. That's why when atypical antipsychotics first go to market, they usually only go with a schizophrenia or acute mania indication just to get the product off the ground and start generating a profit while they finish gathering the data for additional indications like adjunctive treatment of major depressive disorder, bipolar depression, bipolar maintenance (which requires lots of long-term trials), etc.

In this particular case, lumateperone seems to have fewer hallmark side effects of atypical antipsychotics but its antipsychotic effect is less robust as a result, potentially. The 42mg dose was the minimum required to generate a non-inferior antipsychotic effect. More than likely, additional doses will be brought to market for other indications as warranted. If I recall from the pre-clinical trials, they were testing 10mg, 40mg, and 60mg of lumateperone tosylate, which would likely be equivalent to 7mg, 28mg, 42mg. I think there was an additional higher dose mentioned but that it didn't provide enough additional therapeutic benefit to warrant the tolerability issues. By that I mean that somnolence occurred in greater than 25% of patients treated with Caplyta, and going above the 42mg dose just made patients more sleepy but didn't necessarily further improve symptom control.

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6 minutes ago, Iceberg said:

@browri I assume they have bipolar trials in the works right? 

Already WELL underway. Have been for some time.

Two that have already completed for lumateperone as monotherapy for bipolar depression.

https://clinicaltrials.gov/ct2/show/NCT03249376

https://clinicaltrials.gov/ct2/show/NCT02600494

...and one currently recruiting as adjunct to lithium or valproate for bipolar depression:

https://clinicaltrials.gov/ct2/show/NCT02600507

Edited by browri

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18 hours ago, Iceberg said:

Surprised they haven’t done the acute mania/mixed episodes one that most New aps have. 

As am I. We will see I suppose.

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