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Hello everyone. Did a search on the forums and found that there weren't any recent threads compiling everyone's experiences of Rexulti.

I've recently started taking Depakote. I hit a mixed state and we went up to 25mg on loxapine to compensate but it caused too much akathisia and we needed something to stabilize me quickly without using the higher dose of loxapine. Depakote did a better job of that than the oxcarbazepine that I was taking originally.

Now that I've titrated up to 1000mg, I feel like it does a mostly good job at getting me to a better baseline. Just went to 1500mg for 3 days and had to go back down to 1000mg because I started to become depressed. Now that I've reduced it back down, those depressed feelings have gone away. I have more pep back in my step and I'm more engaged in my work. No issue really.

The only problem is that I sometimes have breakthrough anxiety that I manage with 0.5mg of alprazolam or 5mg of loxapine depending on if it leans more towards anxiety/panic or leans more towards intrusive thoughts (respectively).

I would like to rely on PRNs less, and I've been thinking about swapping out my nightly 10mg of loxapine for a daily dose of Rexulti. Could still use the 5mg loxapine PRN along with the alprazolam but I wanted to aggregate people's experiences in one thread to get all the data before I make a decision. My next pdoc appt is 11/17.

Ok, go!

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14 hours ago, Iceberg said:

Rexulti didn't help with sheer anxiety but it helped with depression and all associated symptoms including rumination

That's a good sign. Rumination is a big problem of mine. Intrusive/compulsive/obsessive thoughts. I'm currently using loxapine to treat those and it does a pretty good job but it doesn't have much of an antidepressant effect and doesn't work as well as an adjunct to the Trintellix. I want to get more antidepressant effect out of my antipsychotic and more stabilization.

@Iceberg what doses did you take? How was your response to each? And how do you think it compares to taking Vraylar now?

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3 mgs but it really didn't help any more than 2 mgs so I might not go above 2. The AD response was somewhat fast and it pulled me out of a hole. The rexulti didn't help manic symptoms very much so I'd look at Vraylar if mania is your true concern 

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6 minutes ago, Iceberg said:

3 mgs but it really didn't help any more than 2 mgs so I might not go above 2. The AD response was somewhat fast and it pulled me out of a hole. The rexulti didn't help manic symptoms very much so I'd look at Vraylar if mania is your true concern 

Good pointers. I was thinking of doing 0.5mg for 2 weeks then 1mg for 2 weeks before I decide to go up to 2mg. Like I said above I'm pretty sensitive to akathisia, and while Rexulti has a lower rate of akathisia than Abilify, I've heard that about a lot of atypicals and they still caused me akathisia at the doses recommended in the prescribing information. I always dose lower.

As for the mania side of things, I think I have it pretty well under control with Depakote. There's some room to go up there as well. My hope with Depakote was that I would no longer have to use an AP as my primary anti-manic. Most all APs have mood stabilizing properties even if they aren't good for mania. Latuda was like that. It wasn't a very good anti-manic at all but it still "smoothed the waves" nonetheless. Lamictal is the same way. Not good for acute mania but good at delaying episodes and for smoothing over general mood swings. That's what I'm hoping for out of Rexulti. Like I said, I'm using loxapine now at what most psychiatrists would consider too low a dose to have a meaningful effect on mania. Nevertheless, I still find it incredibly effective for rumination and agitation even if it isn't good for the whole spectrum of mania at this dose.

In all honesty, there's a very good possibility that I won't go above 1mg. Again, I dose low, and I'm not going after mania in its entirety just an intrusive thought process and more antidepressant effect that will lean more towards the calming side of the spectrum.

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  • 2 weeks later...

Spoke with my pdoc about this today, and we decided we're going to give Rexulti a try. Starting at 0.5mg for two weeks and see him again then before titrating up. going to slowly come off loxapine in that time as well.

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24 minutes ago, Iceberg said:

@browri based on my experience with rexulti that definetly seems like a sensible plan...I needed 2 mgs for full antidepressant effect but most don't 

I agree that's possible. But I also have an extremely low akathisia threshold so I may not even tolerate those doses. Also, I'm going for sedation, not stimulation. So I may be fine at the lower doses. I have Vyvanse for stimulation and it may offset some of the sedation. I'm going to take it in the morning for the time being to see how it goes and see how well Vyvanse can offset it. 

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3 hours ago, Iceberg said:

For me higher doses were more sedating as it becomes more antagonistic than agonistic with dopamine. We had to ditch it at 3mgs cuz it wasn't cutting it for manic symptoms

I think it actually works in the opposite direction though. Because of its low intrinsic activity, IF you were to be activated by it, it would be at the higher doses. But for some people, blocking alpha-adrenergic receptors is pretty absolute and sedates them no matter what stimulation. I think @mikl_pls said it was sedating for him at all of the doses.

Did you find Rexulti to be activating in the beginning when you were on lower doses?

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Yes. All that D2 partial agonist stuff is such a headache ?

My doc thought it worked the way I said, but who knows. Abilify has the similar method of action and its more sedation at higher doses but I don't know enough to say your wrong either...the alpha thing is a good point

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11 hours ago, mikl_pls said:

D2 partial agonists act as agonists at presynaptic dopamine autoreceptors, which shuts off dopamine release, and as an antagonist at the postsynaptic dopamine receptors, like most antipsychotics.

That isn't absolute though for all partial agonists though I don't think. For example, aripiprazole and brexpiprazole have no affinity for D2S which is the pre-synaptic receptor. They only touch D2L which is the post-synaptic. Vraylar on the other hand is a partial agonist at both. So while Vraylar should theoretically slow down dopamine release through pre-synaptic agonism, Abilify and Rexulti may only do this to a lesser extent through their actions on the long-form of the receptor, which would be minimal.

Day 2 on 0.5mg of Rexulti and so far so good. After taking my first dose yesterday, it really calmed me pretty quickly and I didn't even think of having to take the extra 5mg loxapine that I would normally take around the middle of the day. It definitely is a strong adrenergic blocker at this dose for sure. Ruminating less. Feel less "angsty". Content is a good word to describe it. Time will tell and it's way to early to make a complete assessment. So far taking it in the morning, and the Vyvanse seems to offset any major sedation it might be causing.

Edited by browri
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1 hour ago, browri said:

That isn't absolute though for all partial agonists though I don't think. For example, aripiprazole and brexpiprazole have no affinity for D2S which is the pre-synaptic receptor. They only touch D2L which is the post-synaptic. Vraylar on the other hand is a partial agonist at both. So while Vraylar should theoretically slow down dopamine release through pre-synaptic agonism, Abilify and Rexulti may only do this to a lesser extent through their actions on the long-form of the receptor, which would be minimal.

Aripiprazole does have affinity for D2S, 0.45 - 3.3 nM with an intrinsic activity of 75%.

Brexpiprazole may too, it just may be that it hasn't been determined yet.

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Just now, mikl_pls said:

Aripiprazole does have affinity for D2S, 0.45 - 3.3 nM with an intrinsic activity of 75%.

Brexpiprazole may too, it just may be that it hasn't been determined yet.

See this is what I get for relying on Wikipedia to be accurate. Do you know of a source with that information so we can update the page cuz that's a pretty crucial pharmacological action. lol.

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18 minutes ago, mikl_pls said:

Once again, it was a combination of sources that I can't find the links to. :X

Indeed I have found plenty of literature indicating that aripiprazole does have functional activity at D2S just can't find the affinity or intrinsic activity.

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I was put on Rexulti for mania and mixed states. I took a combination of gabapentin and tegretol to manage bipolar, but that no longer works. I take 30 MG Zyprexa for schizoaffective. At . 25 MG of rexulti my bipolar is totally controlled, though I still have the gabapentin and  tegretol. It has helped my depression too. I'm looking to drop tegretol and go up on both gabapentin and rexulti. I was pleasantly surprised that such a low dose controlled my bipolar. (I'm more prone to mixed states and mania.) It also is giving me more energy without being too activating. It did seem to relieve anxiety, albeit mildly. I am on two AAPs presently.

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46 minutes ago, CandiedStars said:

I was put on Rexulti for mania and mixed states. I took a combination of gabapentin and tegretol to manage bipolar, but that no longer works. I take 30 MG Zyprexa for schizoaffective. At . 25 MG of rexulti my bipolar is totally controlled, though I still have the gabapentin and  tegretol. It has helped my depression too. I'm looking to drop tegretol and go up on both gabapentin and rexulti. I was pleasantly surprised that such a low dose controlled my bipolar. (I'm more prone to mixed states and mania.) It also is giving me more energy without being too activating. It did seem to relieve anxiety, albeit mildly. I am on two AAPs presently.

I had to do a double take because I thought I was reading one of my own posts when I read your description of how it feels. So far it's been quite settling. I haven't even had the desire for my normal mid-day dose of loxapine. You really don't need much of this stuff. I'm having less fight-or-flight adrenaline like reactions to things around me. Rexulti is a potent alpha-adrenergic blocker even at low doses. But I can also see some of the stimulation too. But it's controlled stimulation. Very subtle. All-in-all I have moments where I feel "a little funny" but it's still quite tolerable. So far the only two things that have settled me well were olanzapine and loxapine. In fact I was going to just go back to olanzapine but we decided to make a pit stop at Rexulti to see if it could work. My pdoc has also said that in his actual use of it, it's pretty different from Abilify.

At this point, my overall outright hypomania is well-controlled with Depakote like when the thoughts race or become disjointed and you become euphoric, but intrusive thoughts, obsessive preoccupations, and agitation I've always dealt with using antipsychotics because anticonvulsants haven't been as effective for these specific symptoms. Like I said, only olanzapine and loxapine have really worked to calm my agitation and quiet my internal monologue enough to focus on what's going on around me. Olanzapine had a good antidepressant and anxiolytic effect. Loxapine might work for some people at 10mg as an augment to an antidepressant but I didn't find loxapine's antidepressive effects to be nearly as effective as olanzapine's. And loxapine has metabolites that are potent norepinephrine reuptake inhibitors so I would take one to calm my thoughts but it would heighten my fight-or-flight response which would in turn just make me more agitated. Then I would take a Xanax and feel REALLY doped up.

I'm more prone to mixed states and hypomania as well. It's when I let them go untreated that they turn into depressive episodes. I can definitely see how Rexulti has antidepressant effect. It makes you feel content really.

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Zyprexa for sure can be quite anxiolytic. It really killed my social phobia, but I still felt some fear.

Rexulti is really slamming that risidual fear down. I feel somewhat low, but it is very weak. I think an increase would help.

I actually read a study where loxapine helped someone with OCD. 

Glad your response to the Rexulti is so good. I really love it. The crazy thing is that abilify gave me rages, yet rexulti really stabilizes me. 

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