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Experiences w/ Risperidone in Combo w/ Lithium or Valproate


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Hello everyone!

So, this is more exploratory than anything. I accept that, as someone with bipolar disorder, taking an antipsychotic might be a necessary part of my maintenance treatment, and lately that has become more evident. I had been taking Rexulti (brexpiprazole) in varying doses since 2017 when I started it with Depakote ER (divalproex, 24-hour) and Trintellix (vortioxetine). Still taking the Depakote (now up to 1500mg), but Trintellix and Rexulti have worked their way out of the equation, as of late.

My medication regimen has taken a more classical turn due to a breakthrough hypomanic episode in Dec./Jan., and I am currently taking a combo of Depakote ER at night along with 0.5mg of Risperdal (risperidone). Because of persistent issues with depression and anxiety, I am also now taking 50mg of Pristiq (desvenlafaxine) each morning along with 50mg of Vyvanse (lisdexamfetamine) for ADHD that I have been taking for some time.

This combo seems to be working fairly well for me. When I started the Risperdal at 0.25mg/day at bedtime, I didn't really notice much difference at all during the day, but I suppose it was nice as a sleep aid. I increased to 0.5mg on Day 4 and I've parked here to try it out for a bit before deciding to increase further. The Risperdal is really to deal with those breakthrough hypomanic/mixed symptoms such as irritability and agitation, which have always been tough for me. In the beginning of my treatment (2014), antipsychotics were used as monotherapy for mood stabilization, but I could never tolerate the doses necessary to calm those symptoms, because I was easily susceptible to EPS like akathisia. Fast-forward a few years, and we've found that using an anticonvulsant as the primary mood stabilizer with the antipsychotic as a secondary has generally served me well without too much incidence of akathisia.

I started Risperdal on June 8th and increased to 0.5mg a few days afterward. So it's been almost 3 weeks at this dose. My experience so far tells me to keep increasing. I'm curious to know people's experiences on Risperdal, particularly in combination with another established mood stabilizing agent like lithium or valproate. I recognize that I take Depakote and that a combo of lithium+Risperdal may not be the same, but the mood stabilizing effects of lithium and valproate are generally regarded with equal respect in most literature for the time being.

Any thoughts on lower dose Risperdal?....particularly in concert with another mood stabilizer?

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39 minutes ago, browri said:

Hello everyone!

So, this is more exploratory than anything. I accept that, as someone with bipolar disorder, taking an antipsychotic might be a necessary part of my maintenance treatment, and lately that has become more evident. I had been taking Rexulti (brexpiprazole) in varying doses since 2017 when I started it with Depakote ER (divalproex, 24-hour) and Trintellix (vortioxetine). Still taking the Depakote (now up to 1500mg), but Trintellix and Rexulti have worked their way out of the equation, as of late.

My medication regimen has taken a more classical turn due to a breakthrough hypomanic episode in Dec./Jan., and I am currently taking a combo of Depakote ER at night along with 0.5mg of Risperdal (risperidone). Because of persistent issues with depression and anxiety, I am also now taking 50mg of Pristiq (desvenlafaxine) each morning along with 50mg of Vyvanse (lisdexamfetamine) for ADHD that I have been taking for some time.

This combo seems to be working fairly well for me. When I started the Risperdal at 0.25mg/day at bedtime, I didn't really notice much difference at all during the day, but I suppose it was nice as a sleep aid. I increased to 0.5mg on Day 4 and I've parked here to try it out for a bit before deciding to increase further. The Risperdal is really to deal with those breakthrough hypomanic/mixed symptoms such as irritability and agitation, which have always been tough for me. In the beginning of my treatment (2014), antipsychotics were used as monotherapy for mood stabilization, but I could never tolerate the doses necessary to calm those symptoms, because I was easily susceptible to EPS like akathisia. Fast-forward a few years, and we've found that using an anticonvulsant as the primary mood stabilizer with the antipsychotic as a secondary has generally served me well without too much incidence of akathisia.

I started Risperdal on June 8th and increased to 0.5mg a few days afterward. So it's been almost 3 weeks at this dose. My experience so far tells me to keep increasing. I'm curious to know people's experiences on Risperdal, particularly in combination with another established mood stabilizing agent like lithium or valproate. I recognize that I take Depakote and that a combo of lithium+Risperdal may not be the same, but the mood stabilizing effects of lithium and valproate are generally regarded with equal respect in most literature for the time being.

Any thoughts on lower dose Risperdal?....particularly in concert with another mood stabilizer?

What specific symptoms are you targeting with the increase- like what do you need it to do better? And do you know your valproate level? I never have and probably never will take risperdal, but I’d think that if your valproate levels are topping out it would make sense to gradually transfer more of the burden to an ap 

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@browri I'll chime in regarding Risperdal (although it's been decades since I took) I was misdiagnosed as BP after acute psychotic episode, initially put on Seroquel, then a stint with Zyprexa...but due to being over sedated, crazy appetite and like you, EPS / akathisia, my pdoc put me on Risperdal. Monotherapy. He said it can have antidepressant effect (which I didn't notice)

Note, I was brand new to psych drugs (since then, never keen on longterm A/Ps). I disliked the side effects, felt groggy / really out of it. Low dose was helpful for sleep, but I didn't feel comfortable staying on it. I would use again as prn if I had acute symptoms. As far as a mood stabilizer, I plan to stay on Lamictal due to the low side effect profile.

Did you stop the Rexulti because it wasn't helping with hypomania (any benefit from Abilify?) And what made you switch to Pristiq? It seems like both Vyvanse & Pristiq could potentially increase agitation/irritability? I've always wondered why someone that needs heavy mood stabilization (or takes multiple A/Ps) would take any dopamine-releasing or agonist type agent? Seems a bit counter.

Is Depakote not enough coverage for hypomania? Sorry if not helpful, just sharing my experience.

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16 hours ago, Iceberg said:

What specific symptoms are you targeting with the increase- like what do you need it to do better?

The risperidone is for a variety of things. I find valproate to be the key mood stabilizer because to me it feels like it turns down the "overall volume" in the brain. Clear hypomania feels good in the beginning, but as it drags on and you finally get to a point that you want to slow down and relax but the volume is too "turned up". It almost feels like you're standing next to a waterfall or having the TV tuned to white noise with the volume turned up. Nails on a chalkboard. With valproate that all kind of evens out a lot, but there's usually breakthrough stuff. I do still have issues sleeping: falling asleep, waking up and not being able to fall back asleep, and my body waking me up too early and being wide awake from the second I open my eyes. That's usually coupled with some snappiness, irritability, agitation, etc. But it's all at a significantly lower level with a solid dose of valproate to keep that under wraps.

I also tend to experience a lot of mixed anxious distress a well. Depressed symptoms are more pronounced but coincide with rapid thought process, agitation, anxiety, etc. This is why I'm on valproate in the first place and also why we think, based on my treatment history, that I've done better on an anticonvulsant+antipsychotic combo than either alone.

16 hours ago, Iceberg said:

And do you know your valproate level?

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When I first started taking valproate, I was taking 1000mg of Depakote ER at bedtime. Worked my way up to 1250mg sometime last year, because, as you can see in 2019 and beginning of 2020, my blood levels were quite low and dose escalation on valproate can be slowly escalating like that as your body gets use to the valproic acid on-board.

Fast-forward and I'm now taking 1500mg Depakote ER at bedtime as of that blood level on 6/2 (which coincidentally was a 62ug/mL). That brief blip on 1/12 to 79 is semi-unexplained at this point. I had just recently increased from 1250mg to 1500mg around that time, so perhaps valproate accumulates a little before your liver picks up the pace.

16 hours ago, Iceberg said:

I never have and probably never will take risperdal, but I’d think that if your valproate levels are topping out it would make sense to gradually transfer more of the burden to an ap 

Honestly, I never thought I'd be willing to take risperidone either, but my husband is taking 1mg of it as his primary mood stabilizer and doesn't have significant side effects from it other than orthostatic hypotension. I don't plan on switching from valproate to risperidone. Rather I hope to be able to use both of them in more modest doses. This is to your point, but to answer a question you probably have: when taking the ER 24-hour formulation of divalproex at bedtime, you generally dose to the point that the blood level taken the following morning (12-hour post-dose) is 80-125ug/mL (50-100 for the regular DR, 12-hour formulation). Clearly mine is not that, but my pdoc doses to tolerability and response. Particularly because of the risks of liver damage over time with valproate, he wants to maintain on a minimum dose possible and would prefer "shaving" off these symptoms with an AAP. His choice of risperidone was because he expected it to cause the least weight gain relative to other generic AAPs, and that was a concern due to the valproate on-board having a weight-positive potential. Risperidone also is less sedating than olanzapine, quetiapine, or ziprasidone for this purpose.

Generally, his statements have proven correct. I don't feel sedated at all during the day. If anything I feel slightly more upbeat. I also haven't put on much, if any, weight. Like I said, I'm currently taking 1500mg divalproex ER and 0.5mg risperidone, but I hope to eventually chip away the divalproex down to 1250mg or 1000mg to instead go up on risperidone to maybe 1mg based on how I feel right now. At least that feels like the general trajectory.

2 hours ago, Blahblah said:

@browri I'll chime in regarding Risperdal (although it's been decades since I took) I was misdiagnosed as BP after acute psychotic episode, initially put on Seroquel, then a stint with Zyprexa...but due to being over sedated, crazy appetite and like you, EPS / akathisia, my pdoc put me on Risperdal. Monotherapy. He said it can have antidepressant effect (which I didn't notice)

Not surprised at all that risperidone as monotherapy didn't have an antidepressant effect, but taken at this low dose and also with an antidepressant on-board, I think I do notice a little bit more pep during the day. Positive emotional responsiveness. My husband has also said that in the time now that I've been taking it he does think I've been less snappy and reactive, a bit more cool and collected. So I appreciate it when it's a difference that he really notices.

2 hours ago, Blahblah said:

Did you stop the Rexulti because it wasn't helping with hypomania (any benefit from Abilify?)

Yes that was basically the issue with Rexulti. As an adjunct to Depakote and an antidepressant, I didn't feel that Rexulti added much in the way of mood-stabilizing capabilities. I really liked it as an antidepressant, and in retrospect the one thing I didn't try was Depakote+Rexulti dual therapy for the bipolar disorder (w/o an antidepressant) and Vyvanse for the ADHD. However, Rexulti didn't seem to have significant anti-manic effects for me. It was positive for my sleep at lower doses, but increasing the dose to achieve additional mood stability didn't gain me anything.

As for Abilify, I will jokingly call it the devil's drug, which it isn't of course, but that's how I was feeling after my 10-day trial of it. I found it to be EXTREMELY stimulating. Like <uncomfortably> stimulating. Akathisia out the wazoo. Then again, that was a point in my treatment when antipsychotics were the primary mood stabilizer. This has changed a bit, but my ability to tolerate dopamine partial agonists has not. I had a 3-month experience with Vraylar at 1.5mg back in 2019, which I aborted for similar reasons. Although admittedly, I was able to obviously tolerate that much longer than Abilify, but the issue was fundamentally the same. Too stimulating. By contrast, I found Rexulti to be quite tolerable and enjoyable compared to Abilify or Vraylar. I actually took Rexulti at night a few hours before bed, and it would help me sleep pretty well. So it may be a dopamine partial agonist, but it is clearly different from the other two.

2 hours ago, Blahblah said:

And what made you switch to Pristiq?

I was taking Trintellix from 2017 until the end of last year. However, I did find over time that it contributed to irritability. I was fairly compatible with it as a medication, but due to the irritability issues and the fact that it didn't do much for my anxiety, when we later decided to resume an antidepressant in my medication regimen, we decided against going back to Trintellix and instead go for something else I had tried in the past and been compatible with. The only other two antidepressants I've been compatible the way I was with Trintellix were Pristiq and Cymbalta. Only reason I discontinued Pristiq in the past was because my insurance wouldn't cover it anymore (it was new, brand-only at the time). And the only reason we discontinued Cymbalta was because I was rediagnosed as bipolar 2 and was in a bit of a hypomanic state having taken an antidepressant as monotherapy my whole life.

2 hours ago, Blahblah said:

It seems like both Vyvanse & Pristiq could potentially increase agitation/irritability?

Potentially, yes. I've taken both for extended periods of time historically, but only separately. This will be the first time I've experienced them together, and it is pretty stimulating. So I'm also considering actually backing down on Vyvanse as well. This was a similar experience for me with Vyvanse and Trintellix. When taking those two together, 40mg was my steady Vyvanse dose, but we would decrease it to as low as 30mg if my Trintellix dose was up to 15mg or 20mg. No dose adjustments for Pristiq really. I started at 50mg, and I happen to do well on it from a depression/anxiety perspective. So I don't see the need to increase it at all. So there is a possibility I may need to decrease the Vyvanse from 50mg back down to 40mg.

2 hours ago, Blahblah said:

I've always wondered why someone that needs heavy mood stabilization (or takes multiple A/Ps) would take any dopamine-releasing or agonist type agent? Seems a bit counter.

Well, I'm 5'11" and 215lbs. 1500mg of Depakote ER to a blood level of only 62ug/mL with 0.5mg of risperidone for someone like me is actually bordering on pediatric treatment. It isn't really heavy mood stabilization at all to be honest. I did talk to my pdoc about this though, because you are right that if you have a basic understanding of the logic behind what dopamine antagonists do and what amphetamines do, then one would think that they effectively neutralize each other, but they really don't.

My pdoc pointed out that bipolar disorder and ADHD actually co-occur quite frequently, and determining a dual diagnosis takes a long time, because the mood disorder needs to be addressed primarily before addressing the attention issue. It's too difficult to determine if you can't focus because you can't focus or if you can't focus because you aren't interested in something. We like to think that as patients we can tell the difference, but it's really tricky and takes a lot of introspection to arrive at that conclusion. So when my pdoc encounters this, he treats the bipolar disorder to euthymia (or slightly dysthymic, because he says that can sometimes be "par for the course" with bipolar disorder), then he adds the stimulant. And as a matter of course, he usually includes an antipsychotic in the cocktail as a safety measure and he will balance/counter-balance the dopamine antagonist against the stimulant, using the lowest dose of each until the patient reports that they are no longer having concentration issues but they simultaneously are not reporting feeling over-stimulated. 

Because amphetamines work upstream at the TAAR1 receptor as an agonist and inhibit VMAT2 to cause expulsion of neurotransmitters into the extraneuronal space, their mechanism is uniquely separate from the dopamine receptor system and that system's feedback loop. A dopamine antagonist actually won't nullify the nerve impulse/potential from TAAR1 agonism and VMAT2 inhibition. However, if you were taking a partial agonist with high intrinsic activity like Abilify (60% agonist at D2 receptors), or if you were taking bupropion with your amphetamines, those medications will actually directly inhibit dopamine release. Agonism of pre-synaptic D2-short receptors by Abilify reduces dopamine release, and Abilify more recently has been found to act more as a partial agonist at pre-synaptic receptors while being an antagonist at post-synaptic receptors for a double-suppression. Bupropion via its NET and DAT inhibition would act as an indirect dopamine agonist similarly, and would have the same suppressing effect on dopamine firing.

This leads into a valid point that activation of dopamine receptors to a high degree can be similarly stabilizing to dopamine antagonists. You can either give someone a dopamine antagonist to throttle the flow of dopamine and restrict how stimulated the receptors can become, or you can give them a dopamine partial agonist to actually desensitize receptors to a certain level of dopamine signaling. Similarly this partial agonist not only binds and activates (60% for Abilify) but also prevents endogenous dopamine (98-100%) from supplanting them. Truly though, bupropion has been regarded as having a significant stabilizing effect in some people with bipolar disorder. Desensitizing the dopamine receptor system reduces dopamine bursting, thus decreasing the risk of precipitating any mood episode as well. And I actually saw a psychologist for a while who did a lot of research into the stabilizing effects of stimulants on those with bipolar disorder, particularly with comorbid ADHD.

2 hours ago, Blahblah said:

Is Depakote not enough coverage for hypomania? Sorry if not helpful, just sharing my experience.

Haha a question that's hard to answer directly. When I was taking Depakote with only Vyvanse, it was usually fairly able to manage hypomania. However, I just generally tended towards the depressive side of things, and I felt better when we reintroduced an antidepressant. Thus we've ended up here with Depakote+Vyvanse+Pristiq, but now instead of being euthymic or sub-dysthymic, I tend towards euthymic or above. Just general snappiness and irritability that are really misplaced. Like to the point that afterwards I'm confused and asking myself why I lashed out. It really isn't terrible because it doesn't happen super frequently, but that's coupled with a general feeling of being on-edge and tense even though a lot of my mental thought processes surrounding anxiety have resolved. And I also obviously don't like the impact I have on other people when I'm like that even if I am apologetic later.

At 0.25mg of Risperdal, I really didn't find it to be too terribly helpful, but 0.5mg for a few weeks and I'm starting to notice a bit of a difference that I like. I feel more settled without feeling all that blunted, and in some ways I feel like I'm more able to take things in stride than I was before. Like the Pristiq did help with general anxiety, but the Risperdal has settled my thoughts even just the slightest bit and I like what I'm seeing.

I think of my brain like one of those sound mixers with all the knobs for the various volumes. Imagine each of the littles ones is a neuron or area of the brain. But there's always a Master volume knob that's bigger than the others. If I had to describe the way I felt in an analogy, taking Depakote is like turning down the overall volume with the Master knob, but you can still have a bunch of little knobs after that that are still turned up too high and might drown out others, so the AAP helps to "smooth" that out.

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11 minutes ago, browri said:

This is to your point, but to answer a question you probably have: when taking the ER 24-hour formulation of divalproex at bedtime, you generally dose to the point that the blood level taken the following morning

Haha i know this from a previous hypothetical pharmacology conversation we had 

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I am on sodium valproate 1500mg

Risperidone 4mg (planning back to 3 soon) 

Duloxetine 180mg

 

Both the SV and the risperidone help me to not relive old arguments at high volume in my head ad nausium

 

I don't know what that is. But brain volume gets to the point where my throat feels hoarse, without speaking out loud. And both of them help that 

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5 hours ago, DogMan said:

I am on sodium valproate 1500mg

Risperidone 4mg (planning back to 3 soon) 

Duloxetine 180mg

 

Both the SV and the risperidone help me to not relive old arguments at high volume in my head ad nausium

 

I don't know what that is. But brain volume gets to the point where my throat feels hoarse, without speaking out loud. And both of them help that 

thanks @DogMan! This is kind of what I was fishing for. Someone on a similar cocktail that was faring well with it. The ruminating / "broken record" thought process is definitely something I'm familiar with. And that pretty accurately describes what I'm after. Issues with rumination. Antipsychotics always do really well for handling those obsessive thought processes, at least for me. 

We did find out that my TSH was high and my T4 was low recently as well, but we increased the Vyvanse a few months ago. It's possible we did this prematurely and we actually needed to increase the levothyroxine because my T4 was low. So we increased the levothyroxine from 75mcg to 88mcg at the beginning of June and it's possible I just need to go back to my original steady Vyvanse dose of 40mg. Then from there work on the risperidone and divalproex doses if necessary.

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