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Couple questions about caplyta. Also question about deplin


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I’m not feeling any better yet. It’s only been 4 days, but I always feel meds within 2-3 days. Is there any chance it could still help me? The only difference I’ve noticed is a mild feeling of dissociation. 
 

Also, does one’s bp presentation change with age? I was always hypo/manic. Hypomanic was my baseline. I’d get one short depressive episode a year. Now that I’m 42, I have spent most of the past 3 years depressed. I’ve had one manic episode. 
 

The only thing that got me out of the depression was requip. I felt amazing. I was so productive. But it seems to have quit working. 
 

Does caplyta ward off mania at all? I’m thinking of asking my doctor to stop my abilify because maybe I’m over medicated now that I’m rarely manic or even hypo. 
 

However, I’m not convinced that this isn’t a medical issue. My symptoms are lack of focus, lack of energy, and lack of motivation. I just feel so freaking bored but have no desire to do anything. 
 

A couple months ago, I went to the doctor for feeling extra tired. I had low folate. So I started taking methylfolate. I’ve seen deplin mentioned here a lot and was wondering if that’d be a better option. Or if insurance covers it. I have Medicaid. 

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On 3/5/2022 at 12:05 PM, iLove said:

I’m not feeling any better yet. It’s only been 4 days, but I always feel meds within 2-3 days. Is there any chance it could still help me? The only difference I’ve noticed is a mild feeling of dissociation. 

Hey @iLove! Not sure if you're still taking this, but it takes 5 days to reach "steady state" on Caplyta, and one of its effects is serotonin reuptake inhibition, like an antidepressant. So initial side effects may have some dizzines or dazed feeling. And the positive mood effects of Caplyta can take at least 2 weeks if not more to become apparent.

On 3/5/2022 at 12:05 PM, iLove said:

Also, does one’s bp presentation change with age? I was always hypo/manic. Hypomanic was my baseline. I’d get one short depressive episode a year. Now that I’m 42, I have spent most of the past 3 years depressed. I’ve had one manic episode. 

Newer science is showing that bipolar disorder is actually a neurodegenerative disease much like Parkinson's, and without treatment it's progressive. Onset is around young adulthood (20s), and if it goes without treatment, symptoms get worse with time. Additionally, the longer someone with active bipolar disorder goes without treatment, the lower the likelihood that they will respond to treatment if they finally start (i.e. medicines that might have worked if you started them in your 20s might not work if you wait to start them until you're 40 or 50). When they do autopsies of people with bipolar disorder that weren't properly treated throughout their lives, their brains are riddled with evidence of glutamate neurotoxicity.

Crazy as this may sound, but some studies even show that people who have had bipolar disorder and treated it all their lives find they suddenly don't need medication for it in old age or don't need as much medication to maintain.

In my personal experience, the issue I always complained about when I was younger was depression. But I remind myself that those times when my depression was at some of its worst, I wasn't diagnosed as bipolar and being properly treated with mood stabilizers. I was still on the MDD merry-go-round of antidepressants. I still have problems with depression since being re-diagnosed as bipolar II, but I'm much more aware of my hypomania now than I was before I was re-diagnosed. I don't think this is necessarily because hypomania has become a more prominent problem, but rather because I didn't see it for what it was: a problem.

While hypomania feels good, I also have become very self-conscious about the things I do when I am hypomanic, and that makes me view my hypomania as more of a problem. I attribute my DUI to a combination of poor judgement and hypomania, but for the longest time, I didn't understand the hypomania part, and I spent so much time beating myself up for making a stupid decision and not understanding that the DUI was part of a bigger problem that I wasn't addressing.

So do I think someone's bipolar presentation changes with age? Yes, science says that it's definitely possible. Do I think that humans are capable of ignoring obvious things right under their nose, understanding them, and then thinking that something suddenly changed when they had a eureka moment? Also yes. :) 

On 3/5/2022 at 12:05 PM, iLove said:

The only thing that got me out of the depression was requip. I felt amazing. I was so productive. But it seems to have quit working. 

There is definitely something to using Requip (ropinirole) or Mirapex (pramipexole) to treat bipolar depression. No way they'll get an FDA-approved indication at this point, but dopamine agonists are definitely used third-line off-label for bipolar depression.

On 3/5/2022 at 12:05 PM, iLove said:

Does caplyta ward off mania at all? I’m thinking of asking my doctor to stop my abilify because maybe I’m over medicated now that I’m rarely manic or even hypo. 

It is an antipsychotic, so it's possible. However, currently Caplyta is only approved to treat the depressive side of bipolar I or II either alone or in combination with lithium or valproate, and Intra-Cellular Therapies isn't currently pursuing a mania indication that I know of. The compound is currently in trial for

1. Adjunct to an antidepressant for MDD
2. Mixed features in MDD and Bipolar Disorder

They're also working on what they code-named LLAI (Lumateperone Long-Acting Injectable), most likely for schizophrenia, but it's possible that they could pursue an indication for the use of LLAI as bipolar maintenance (most likely in combination with lithium or valproate).

They are also developing a nearly identical molecule called ITI-333-ODT-SL, which takes lumateperone, replaces all of the hydrogen atoms in the molecule with deuterium and makes it into an orally disintegrating sublingual tablet. This form is being trialed for agitation in Alzheimer's disease, dementia-related psychosis, and depressive disorders in the elderly. Replacing hydrogen with deuterium in molecules doesn't generally change the actions of the molecule, it just makes the molecule heavier, and therefore harder for the body to metabolize and eliminate. This changes the pharmacokinetics and generally makes deuterated forms of pharmaceuticals persist longer than their hydrogenated counterparts.

As for the Abilify, I'm not sure it makes a whole lot of sense while you're taking Caplyta. They kind of cancel each other out because Caplyta is an antagonist (total blocker) whereas Abilify is a partial agonist (partially activates).

However, if Caplyta doesn't work out for you but you've done well on Abilify and Requip helps your depression, then you might do well on Vraylar.

On 3/5/2022 at 12:05 PM, iLove said:

A couple months ago, I went to the doctor for feeling extra tired. I had low folate. So I started taking methylfolate. I’ve seen deplin mentioned here a lot and was wondering if that’d be a better option. Or if insurance covers it. I have Medicaid. 

The L-methylfolate should enhance Caplyta's antidepressant effect via serotonin reuptake inhibition. You could try for Deplin, and really what you're getting is pharmaceutical quality, but it may not necessarily be a better product than OTC L-methylfolate. And insurance is usually difficult about covering it.

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@browri Omg thank you so much for all of that information! It’s all so interesting. I’m so glad I decided to check in today. 
 

At my appointment last week, we stopped abilify (well I did it myself a few weeks ago without telling him) and upped requip and I’m back out of the depression. 
 

I’m going to have to start reading studies because I’d love to have more knowledge about my disorder. Do you just Google random stuff? 
 

And how did you learn so much about the specific actions of meds? I can tell I’m on a little too much of an upswing now that I’ve been off abilify for a month. But I really don’t want to go back on it and risk depression again. 

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2 hours ago, iLove said:

At my appointment last week, we stopped abilify (well I did it myself a few weeks ago without telling him

Just wondering, does he feel the need to add/change anything for (hypo)mania coverage ? 
 

On 4/2/2022 at 3:55 PM, browri said:

It is an antipsychotic, so it's possible

I’ve heard a few docs put it in the rexulti category (not method of action, more in terms of effect) In that it can definitely help BP depression and maybe mixed but the hypo/manic directly is still an “ehhhh…” at this point 

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17 hours ago, iLove said:

At my appointment last week, we stopped abilify (well I did it myself a few weeks ago without telling him) and upped requip and I’m back out of the depression. 

Good to hear!! 🥳

17 hours ago, iLove said:

I’m going to have to start reading studies because I’d love to have more knowledge about my disorder. Do you just Google random stuff? And how did you learn so much about the specific actions of meds?

Being obsessive, hypomanic, and hyperfocused can have its advantages. 😅 I've always had a really strong desire to understand how things work. The "under-the-hood" of it all. I've always been that way about technology/gadgets, but I find I'm the same way about psychiatry and understanding how the brain works, why it doesn't work when it's supposed to, and how medications change our brain state. I've always kind of just been fascinated by it.

I don't Google randomly necessarily as much as I start on a topic I find interesting and follow the trail of info. I usually end up very far from where I started and absorbed more information than I planned. Some of the stuff about mechanism of action you can find on a medication's Wiki page in the pharmacology/pharmacodynamics sections. However, you generally have to go beyond that with something like scholar.google.com (favorite).

17 hours ago, iLove said:

I can tell I’m on a little too much of an upswing now that I’ve been off abilify for a month. But I really don’t want to go back on it and risk depression again. 

Keep an eye on it. Remember what I said about bipolar disorder being progressive. Each mood swing almost invariably has an opposite swing. So when you go into (hypo)mania your brain is pretty much flooded with glutamate. When you end up in glutamate neurotoxicity, this has inflammatory effects in the brain that end up translating into bipolar depression.

15 hours ago, Iceberg said:

I’ve heard a few docs put it in the rexulti category (not method of action, more in terms of effect) In that it can definitely help BP depression and maybe mixed but the hypo/manic directly is still an “ehhhh…” at this point 

I have to imagine that if they noticed it had any anti-manic effect they would have gone for an indication. A schizophrenia indication is the easy way to get in the door, but a bipolar depression indication would be difficult to get. With antipsychotics, mania is usually an easier indication to get like schizophrenia. That is, unless, the antimanic effect was so poor that Intra-Cellular really thought they wouldn't make it with the indication. Other than Caplyta and Rexulti, the only other antipsychotic that really falls into that category is Latuda. Generally speaking, Latuda isn't regarded as having much anti-manic effect. Although, it does seem to have good efficacy in mixed depression.

The way episodes are defined now for mixed, you would define someone as mixed (50/50), mixed manic, or mixed depressive depending on which symptoms are more prominent. Seroquel seems to be good across the spectrum. Rexulti and Latuda are examples of medications that are relegated to the mixed depressive category, whereas Vraylar and Abilify are generally better for mixed manic than mixed depressive when compared to Seroquel, for example.

I sincerely hope that they go for a bipolar maintenance indication for the long-acting injectable version in combination with either lithium or valproate. That would be an easy one. I ended up buying some stock in Intra-Cellular Therapies over the past year or so betting on their bipolar depression approval, which turned out to be a good bet, and a lucrative one too.

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1 hour ago, browri said:

Rexulti and Latuda are examples of medications that are relegated to the mixed depressive category, whereas Vraylar and Abilify

I’d also say, possibly because of moving away from straight d2 antagonism and “dirty” side effect profiles that sedation has become more of an undesirable in the shiny new meds - the aaps seroquel and zyprexa are both intentionally used for sedating qualities, but if seems now that the goal is to address the mania in ways besides just knocking the energy out of someone. That’s probably tied to metabolic issues of the sedating meds too 

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On 4/6/2022 at 5:47 PM, Iceberg said:

Just wondering, does he feel the need to add/change anything for (hypo)mania coverage ? 
 


 

No, and I think I might be hypomanic. I’m so on edge that I’m uncomfortable. I’m super irritable and can’t relax my face. But I’m terrified to go back on abilify and get depressed again. I was thinking maybe vraylar would be good. 

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On 4/7/2022 at 9:48 AM, browri said:

Good to hear!! 🥳

Keep an eye on it. Remember what I said about bipolar disorder being progressive. Each mood swing almost invariably has an opposite swing. So when you go into (hypo)mania your brain is pretty much flooded with glutamate. When you end up in glutamate neurotoxicity, this has inflammatory effects in the brain that end up translating into bipolar depression.

Rexulti and Latuda are examples of medications that are relegated to the mixed depressive category, whereas Vraylar and Abilify are generally better for mixed manic than mixed depressive when compared to Seroquel, for example.


 

 

 

Forgive me, I don’t know how to multi quote.

 

Thank you! It is welcome relief! 
 

Wow so interesting. i guess that’s why people complain about crashing after a manic episode. I’ve never experienced the crash. But the way you describe makes a lot of sense and makes me think I need get back on abilify asap. 
 

I was hypo/manic the whole time I was on latuda so I agree with that. 
 

I’m going to call my doctor tomorrow. I wonder if vraylar is a better option. I wonder if I’m in a mild mixed episode. It definitely isn’t bad like when I was hospitalized. But I am just so pissed off. 

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On 4/7/2022 at 12:29 PM, Iceberg said:

I’d also say, possibly because of moving away from straight d2 antagonism and “dirty” side effect profiles that sedation has become more of an undesirable in the shiny new meds - the aaps seroquel and zyprexa are both intentionally used for sedating qualities, but if seems now that the goal is to address the mania in ways besides just knocking the energy out of someone. That’s probably tied to metabolic issues of the sedating meds too 

This is true. And most of the AAPs like Seroquel and Zyprexa that do cause sedation, do so via H1 (histamine) antagonism. Because this causes one to be more sedentary and have reduced physical activity, it generally contributes to weight gain.

14 hours ago, iLove said:

No, and I think I might be hypomanic. I’m so on edge that I’m uncomfortable. I’m super irritable and can’t relax my face. But I’m terrified to go back on abilify and get depressed again. I was thinking maybe vraylar would be good. 

Vraylar may be a good option because it seems to have more efficacy in bipolar depression than Abilify, but it will be somewhat similar to Abilify in effect. So if you can tolerate Abilify, you should be able to tolerate Vraylar.

14 hours ago, iLove said:

Forgive me, I don’t know how to multi quote.

So the '+' button next to the 'Quote' link will allow you to select multiple responses to quote. Once you've selected them, you select the Multi-quote button in the lower right-hand corner. It's tricky though because there's usually a banner ad across the bottom of the page that blocks the Multi-quote button. You won't be able to see the button until you hide the ad using the arrow button in the lower left-hand corner.

14 hours ago, iLove said:

Wow so interesting. i guess that’s why people complain about crashing after a manic episode. I’ve never experienced the crash. But the way you describe makes a lot of sense and makes me think I need get back on abilify asap. 

It's funny how physics still applies even in the brain. "For every action, there is an equal, but opposite, reaction, unless acted upon by an outside force." So mania usually ends up in depression. Although I have known some people to have depressions that progress into manias. Medication would be your "outside force".

14 hours ago, iLove said:

I was hypo/manic the whole time I was on latuda so I agree with that. 

When I took Latuda, I was only taking it as my "primary" mood stabilizer along with Lamictal. I kept having issues with irritability/agitation, and we kept increasing the dose. It was around 80mg that I started having akathisia, and the snappiness of my mood wasn't getting any better. Ultimately I found that an anticonvulsant like Depakote as my primary mood stabilizer was better and using a more calming AP like Risperdal as a secondary mood stabilizer when I'm having difficult mood issues but particularly in the Fall/Winter when I just can't get through without an antidepressant. Depakote is enough usually, but if I get depressed, an antidepressant is the only thing that seems to fix it, but the antidepressant does still destabilize me a bit. So the secondary mood stabilizer is needed in that case.

14 hours ago, iLove said:

I’m going to call my doctor tomorrow. I wonder if vraylar is a better option. I wonder if I’m in a mild mixed episode. It definitely isn’t bad like when I was hospitalized. But I am just so pissed off. 

Even if Vraylar isn't a better option (and your pdoc will know), it's best not to let the agitation go. Your pdoc should know about it anyway and might have an idea of where to go next, even if it isn't Vraylar. Definitely good to ask about it though. They may be open to the idea since you've tolerated Abilify in the past.

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