Zyprexa vs Risperdal for OCD

[JJ17]

I’m on high dose SSRI and need something to help the OCD I still have. Badicsllt the only options are switch SSRIS again, or add a med. After lots of research it seems like either Risperdal or Zyprexa would work best. 

Anyone taken it with an SSRI to try to treat OCD? 

I also found one graph showing the dopamine blocking action of both meds and it seems Zyprexa is more potent, yes? I’m also confused as to how they block SERT, as wouldn’t that kind of do the opposite of the SSRI? Or maybe I misunderstand how they work. 

Also: weight gain isn’t a concern. If anything a plus as I’ve been underweight my entire life and cannot put on weight even when downing protein shakes daily. But ideally whichever of the two boosts the SSRI better or has more synergy would be better. I take Zoloft at the moment. 

Edited November 6, 2018 by JJ17

[Catwoman]

I'm interested in this as well. I take clomipramine and I still have 'residue' of OCD obsessive thinking (repetitive words) and on bad days I wish there was something I could take to help the clomipramine. So I was thinking of a low dose risperidone. Zyprexa/olanzapine might work. But....I'm not overweight, but I don't want to gain any either.

@browrican probably answer your question about the dopamine blocking action.

By the way, have you ever tried Anafranil/ clomipramine?

[browri]

3 hours ago, JJ17 said:

I’m on high dose SSRI and need something to help the OCD I still have. Badicsllt the only options are switch SSRIS again, or add a med. After lots of research it seems like either Risperdal or Zyprexa would work best. 

Anyone taken it with an SSRI to try to treat OCD? 

I also found one graph showing the dopamine blocking action of both meds and it seems Zyprexa is more potent, yes? I’m also confused as to how they block SERT, as wouldn’t that kind of do the opposite of the SSRI? Or maybe I misunderstand how they work. 

Also: weight gain isn’t a concern. If anything a plus as I’ve been underweight my entire life and cannot put on weight even when downing protein shakes daily. But ideally whichever of the two boosts the SSRI better or has more synergy would be better. I take Zoloft at the moment. 

SSRIs do work by blocking SERT. I know that may seem counter-intuitive, but consider how they work. The SERT is an abbreviation for the serotonin transporter. It is responsible for returning serotonin to the sending neuron once serotonin has "delivered its message" to the receiving neuron. This process is referred to as reuptake. For people with depression, the hypothesis goes that their serotonin levels may be low. SSRIs work by blocking serotonin reuptake by the transporter so that more serotonin stays in the synapse between two neurons instead of returning to the originating neuron. This increases overall serotonergic activity.

Antipsychotics are sometimes used in treatment-resistant OCD as an augment to high dose SSRI. Seroquel, Risperdal, and Zyprexa are generally preferred for this indication. No one is entirely sure why they work so well in OCD, but we can take a few hints from how they work in other conditions. They block 5HT_2A receptors which causes dopamine release, and this would be a soothing action. Serotonin is a stimulating neurotransmitter. Dopamine is typically a calming one. For many people, when you increase serotonin levels, dopamine activity can decrease, which is why many experience tolerability issues starting SSRIs due to things like insomnia and agitation. By introducing an atypical antipsychotic, you start blocking serotonin receptors. This also may seem counter-intuitive, but consider that not all serotonin receptors should be activated. Some should be blocked. So the point of an atypical antipsychotic as an adjunct to an antidepressant is to "tune" the effect of the antidepressant.

Dopamine blockade is also important. Risperdal probably has the strongest effect on D₂ receptors followed by Zyprexa and then Seroquel. The do all have weight gain potential, but in lower doses Risperdal can be more forgiving than Seroquel or Zyprexa. My partner takes 10mg of Lexapro and 1mg of Risperdal. He did say it took some time to adjust but he actually likes the calm collectiveness that it gives him. Less ruminating. I feel the same way about Rexulti.

[Rabbit37]

I’m sorry, I don’t know all the science behind it, but can say that risperdal was extremely effective in curbing ocd for me. And it’s fast acting as well, I noticed relief in three days. 

Two things, though... my pdoc stressed repeatedly that risperdal is meant to be a short term med, not a long term solution. And, I had to stop because of high prolactin levels, which can cause bone loss. I was on 2-3mg. 

[CeremonyNewOrder]

In the literature, I've read that low dose risperidone can be effective for treatment reistant OCD. Not sure about Zyprexa. 

[JJ17]

Here’s a graph I found from this website actually (on the Serequel sticky thread) that shows them: 

If that is correct Zyprexa seems stronger blocking dopamine but not certain. 

Turn pic sideways to view it: 

Zyprexa hits the minium for “antipsychotic thereshold occupancy” at roughly 7.5mg. While risperdial takes 2mg to hit the minimum. Interesting but not sure how accurate it is. As doesn’t risperdial come in 0.25mg and 0.5mg doses? If so it seems like it doesn’t reach its therpatic dopamine effects until 2mg - at least for its antipsychotic wise.

For anxiety and OCD augmentation perhaps 0.5mg or 1mg would be enough? 

Edited November 7, 2018 by JJ17

[jt07]

I had good luck with low dose Risperdal. Zyprexa was too sedating for me.

[JJ17]

31 minutes ago, jt07 said:

I had good luck with low dose Risperdal. Zyprexa was too sedating for me.

What did you use it for? I’m only looking for it’s OCD and anxiety properties. 

I don’t have any hallucinations or anything psychotic wise. Rather trying to treat OCD/anxiety that only somewhat responds to high dose SSRIS 

[JJ17]

13 hours ago, browri said:

SSRIs do work by blocking SERT. I know that may seem counter-intuitive, but consider how they work. The SERT is an abbreviation for the serotonin transporter. It is responsible for returning serotonin to the sending neuron once serotonin has "delivered its message" to the receiving neuron. This process is referred to as reuptake. For people with depression, the hypothesis goes that their serotonin levels may be low. SSRIs work by blocking serotonin reuptake by the transporter so that more serotonin stays in the synapse between two neurons instead of returning to the originating neuron. This increases overall serotonergic activity.

Antipsychotics are sometimes used in treatment-resistant OCD as an augment to high dose SSRI. Seroquel, Risperdal, and Zyprexa are generally preferred for this indication. No one is entirely sure why they work so well in OCD, but we can take a few hints from how they work in other conditions. They block 5HT_2A receptors which causes dopamine release, and this would be a soothing action. Serotonin is a stimulating neurotransmitter. Dopamine is typically a calming one. For many people, when you increase serotonin levels, dopamine activity can decrease, which is why many experience tolerability issues starting SSRIs due to things like insomnia and agitation. By introducing an atypical antipsychotic, you start blocking serotonin receptors. This also may seem counter-intuitive, but consider that not all serotonin receptors should be activated. Some should be blocked. So the point of an atypical antipsychotic as an adjunct to an antidepressant is to "tune" the effect of the antidepressant.

Dopamine blockade is also important. Risperdal probably has the strongest effect on D₂ receptors followed by Zyprexa and then Seroquel. The do all have weight gain potential, but in lower doses Risperdal can be more forgiving than Seroquel or Zyprexa. My partner takes 10mg of Lexapro and 1mg of Risperdal. He did say it took some time to adjust but he actually likes the calm collectiveness that it gives him. Less ruminating. I feel the same way about Rexulti.

Makes sense. Only thing is I always thought serotonin was more the calm/content chemical while dopamine was more the motivation/stimulating/pleasure chemical? Or I guess noradrenaline is the most stimulating of the three. I always knew SSRIS worked by increasing SERT in the synapse. So I take 5HTP in addition as SSRIS only affect reuptake. Taking 5HTP with SSRI will combine SERT synthesis and SERT reuptake. Which I wouldn’t advise for most people. Although for me it’s been the only way to make SSRIS work half decent. Even at 200mg Zoloft I still need some 5HTP to help it work. 

But for the atypical antipsychotics it seems they work as SERT blockers on quite a few important sites, no? 

From Wikipedia on Risperdals actions: 

Site	Ki (nM)	Action
5-HT1A	423	Antagonist
5-HT1B	14.9	Antagonist
5-HT1D	84.6	Antagonist
5-HT2A	0.17	Inverse agonist
5-HT2B	61.9	Inverse agonist
5-HT2C	12.0	Inverse agonist
5-HT5A	206	Antagonist
5-HT6	2,060	Antagonist
5-HT7	6.60	Irreversible antagonist[42]
α1A	5.0	Antagonist
α1B	9.0	Antagonist
α2A	16.5	Antagonist
α2B	108	Antagonist
α2C	1.30	Antagonist
D1	244	Antagonist
D2	3.57	Antagonist
D2S	4.73	Antagonist
D2L	4.16	Antagonist
D3	3.6	Inverse agonist
D4	4.66	Antagonist
D5	290	Antagonist
H1	20.1	Inverse agonist
H2	120	Inverse agonist

Edited November 7, 2018 by JJ17

[notloki]

Most AP/AAP's have moderate to strong antidepressant action, most all affect serotonin sites. 

[echolocation]

i have ocd symptoms and am on 0.75 mg risperidone and 225 mg effexor. it works excellently for me. it stops my thinking spirals, gives me the ability to focus, and generally slows my brain down a little bit. i used to take 150 mg zoloft, but moved to effexor because i needed something more sedating. effexor is great at zapping my day to day anxiety, but risperidone covers the ruminating and obsessing.

i take the little 0.25 tablets. my psych told me to watch out for the prolactin stuff, but he said it wasn't likely under 1 mg. he also didn't want to go about 1 mg or so for OCD, but luckily 0.75 has worked great for me. i started at 0.25 and bumped it up by 0.125 or 0.25 whenever i felt like i was getting a lot of breakthrough symptoms, but for the last year or so i haven't needed to raise it anymore. i also occasionally use it like a PRN when i'm ruminating badly or really anxious. an extra 0.25 seems to settle things down. i get no side effects from it that i can notice. i have gained a little weight since taking it and have gone up a pants size, but it's possible that's just a lifestyle thing.

i'd say give it a try. like rabbit said, it kicks in fast. i noticed the change in a few days. one thing i will say is i get crazy withdrawal from it, but i'm not sure that's too common. it's like my brain goes into overdrive once it's not being sedated, and physically and mentally i move really fast. it goes away within an hour of taking the dose. 

[Velvet Elvis]

Intuniv is keeping mine under control along with the vocal tics that come with it.  I've never taken it but have you tried Abilify?  Zyprexa long term is a really bad idea unless you have no other options.  

[cakepop]

[deleted]

Edited April 7, 2019 by cakepop

[JJ17]

2 hours ago, Gatorgirl said:

I need help too. I have severe OCD and I’m on 200 mg Anafranil/Clomipramine, 2 mg Rexulti, and 2 mg Klonopin... I’m STILL depressed and symptomatic! I see my pnurse soon. Is Seroquel XR helpful at all for a calming effect? Was going to ask for that but now I’m thinking about asking for risperdal.

I personally wound avoid Seroquel but that’s just IMO and the research I have done. 

Basically Seroquel at anything under 500mg (I believe 300mg or 500mg) is basically a glorified super strong anti-histamine. Like Benadryl is an anti-histamine. So Seroquel will make you sedated and tired, that’s an extremely common side effect. Although it’s because it heavily binds to anti-histamine receptors. 

So I believe you need to be on 500mg + before it actually starts to have action on dopamine, etc. Which is crazy but from what I have researched seems mostly true - and most doctors don’t know about it for some reason. 

Similar to Effexor it becomes a different drug at different doses. At 37.5mg or 75mg it’s basically an SRI. At 150mg + Effexor becomes an SNRI. Then at 300mg Effexor possibly (not known for certain but some believe it does) even reuptakes dopamine a tad. So some meds just totally change into different meds once the dosage is changed. Most doctors sadly don’t know this. 

Effexors SRI effects basically  top out at 75mg where it has above 80 to 85% SERT Occupancy. Increasing it to 150mg it still has the same occupancy. So increasing the Effexor dose is pointless UNLESS you want it to become an SNRI. That’s another thing most doctors sadly don’t seem to know. Which means they could put you on the wrong dose, etc. Same goes for Seroquel many times they’ll put someone on 50mg and wonder why it doesn’t work; and that the person is tired all the time... 

But I’m not a doctor so this is all just my opinion, and based on research I have done. 

Edited November 7, 2018 by JJ17

[browri]

10 hours ago, JJ17 said:

Makes sense. Only thing is I always thought serotonin was more the calm/content chemical while dopamine was more the motivation/stimulating/pleasure chemical? Or I guess noradrenaline is the most stimulating of the three. I always knew SSRIS worked by increasing SERT in the synapse. So I take 5HTP in addition as SSRIS only affect reuptake. Taking 5HTP with SSRI will combine SERT synthesis and SERT reuptake. Which I wouldn’t advise for most people. Although for me it’s been the only way to make SSRIS work half decent. Even at 200mg Zoloft I still need some 5HTP to help it work. 

Don't confuse serotonin with its transporter. They are still distinctly separate things. Yes, taking 5-HTP can increase serotonin synthesis (not SERT synthesis) and in combination with inhibition of the transporter, this would have a net effect of higher serotonin in the synapse.

Serotonin is responsible for pleasure in a way but it's more about our social interactions and how we relate to other people. Dopamine is the pleasure chemical, but it is relaxing. This is why blocking 5HT_2A causes dopamine release and subsequently, sedation. If you increase serotonin, the activation of serotonin receptors inhibits dopamine release. The combination of high serotonin and low dopamine is activating for most people and is one of the hypotheses behind SSRI-induces hypomania.

10 hours ago, JJ17 said:

But for the atypical antipsychotics it seems they work as SERT blockers on quite a few important sites, no? 

From Wikipedia on Risperdals actions: 

Site	Ki (nM)	Action
5-HT1A	423	Antagonist
5-HT1B	14.9	Antagonist
5-HT1D	84.6	Antagonist
5-HT2A	0.17	Inverse agonist
5-HT2B	61.9	Inverse agonist
5-HT2C	12.0	Inverse agonist
5-HT5A	206	Antagonist
5-HT6	2,060	Antagonist
5-HT7	6.60	Irreversible antagonist[42]
α1A	5.0	Antagonist
α1B	9.0	Antagonist
α2A	16.5	Antagonist
α2B	108	Antagonist
α2C	1.30	Antagonist
D1	244	Antagonist
D2	3.57	Antagonist
D2S	4.73	Antagonist
D2L	4.16	Antagonist
D3	3.6	Inverse agonist
D4	4.66	Antagonist
D5	290	Antagonist
H1	20.1	Inverse agonist
H2	120	Inverse agonist

Again, don't confuse the SERT with the receptors. On the receiving and sending neurons there are receptors where serotonin bonds to deliver its message. The serotonin transporter just returns serotonin to the receptor on the sending neuron after serotonin has bound to the receiving neuron and been subsequently released back into the synapse. All of the effects that you are seeing for Risperdal above are not for the serotonin transporter (SERT) but for post-synaptic receptors. Risperdal's actions at those receptors can result in more serotonin release such as antagonism of pre-synaptic 5HT_1A receptors.

Some AAPs do have effect on the SERT, but I don't believe that Risperdal is one of them. Abilify and Rexulti do to a certain degree. I believe Seroquel does as well and maybe Zyprexa.

[CeremonyNewOrder]

14 hours ago, JJ17 said:

What did you use it for? I’m only looking for it’s OCD and anxiety properties. 

I don’t have any hallucinations or anything psychotic wise. Rather trying to treat OCD/anxiety that only somewhat responds to high dose SSRIS 

a low dose anti-psychotic can be used to augment your antidepressant if an antidepressant alone won't work 

[jt07]

You don't need to be psychotic to take an antipsychotic. I have major depression without psychosis, and I take Abilify, and it has been a godsend. Antipsychotics are useful for quite a few mental disorders. It's just unfortunate that they carry the name antipsychotic.

[JJ17]

9 hours ago, browri said:

Don't confuse serotonin with its transporter. They are still distinctly separate things. Yes, taking 5-HTP can increase serotonin synthesis (not SERT synthesis) and in combination with inhibition of the transporter, this would have a net effect of higher serotonin in the synapse.

Serotonin is responsible for pleasure in a way but it's more about our social interactions and how we relate to other people. Dopamine is the pleasure chemical, but it is relaxing. This is why blocking 5HT_2A causes dopamine release and subsequently, sedation. If you increase serotonin, the activation of serotonin receptors inhibits dopamine release. The combination of high serotonin and low dopamine is activating for most people and is one of the hypotheses behind SSRI-induces hypomania.

Again, don't confuse the SERT with the receptors. On the receiving and sending neurons there are receptors where serotonin bonds to deliver its message. The serotonin transporter just returns serotonin to the receptor on the sending neuron after serotonin has bound to the receiving neuron and been subsequently released back into the synapse. All of the effects that you are seeing for Risperdal above are not for the serotonin transporter (SERT) but for post-synaptic receptors. Risperdal's actions at those receptors can result in more serotonin release such as antagonism of pre-synaptic 5HT_1A receptors.

Some AAPs do have effect on the SERT, but I don't believe that Risperdal is one of them. Abilify and Rexulti do to a certain degree. I believe Seroquel does as well and maybe Zyprexa.

Thanks, awesome post! I was using SERT as a blanket abbreviation, didn’t realize it was meant for the transporter. Good to know. 

Also for Risperdal and dopamine Whenever I heard they “block dopamine” I always thought it meant it decreased it. Is the goal of Risperdal to decrease dopamine activity and/or levels in the synapse or is it the opposite and increases dopamine activity? 

That’s what I got confused about when reading about them. As I always thought by reducing dopamine either in the synapse or by other means, this would cause the medications therapeutic effect. As I remember reading somewhere that increased dopamine activity was believed to cause psychotic symptoms. Is that correct or perhaps I read it wrong? 

[browri]

On 11/7/2018 at 6:10 PM, JJ17 said:

Thanks, awesome post! I was using SERT as a blanket abbreviation, didn’t realize it was meant for the transporter. Good to know. 

Also for Risperdal and dopamine Whenever I heard they “block dopamine” I always thought it meant it decreased it. Is the goal of Risperdal to decrease dopamine activity and/or levels in the synapse or is it the opposite and increases dopamine activity? 

That’s what I got confused about when reading about them. As I always thought by reducing dopamine either in the synapse or by other means, this would cause the medications therapeutic effect. As I remember reading somewhere that increased dopamine activity was believed to cause psychotic symptoms. Is that correct or perhaps I read it wrong? 

They do reduce dopamine signaling in some ways and increase it in others. Or rather in different brain regions. For example, blocking dopamine signaling in the striatum of the brain can result in movement disorders but blocking it in the mesocortical pathways can prevent psychosis. By blocking 5HT_2A the way that atypical antipsychotics do, they increase dopamine release in certain areas of the brain that would be the locus for the movement related side effects from AAPs. Blocking or activating certain serotonin receptors can attenuate some of the side effects of blocking dopamine.

Increased dopamine release in certain brain pathways can have positive effects on depression, which is why it has become so popular to add an AAP to an antidepressant when an antidepressant alone fails.

Also keep in mind that there are both pre-synaptic and post-synaptic receptors. Specifically at the pre-synaptic ones, if there isn't any dopamine binding to those receptors, the brain things it needs to release more to compensate. So blocking dopamine receptors does reduce dopamine signaling but can still increase dopamine release into the synapse. Confusing, I know. But that's how it works supposedly.

[JJ17]

Makes sense for the most part. I just don’t like the idea of increasing dopamine as almost any dopamine boosting agent (even simple l-tyrosine) worsened OCD/obsessions for me.

Which dopamine does play a key role in obsessions/addictions, at least of the major known chemicals. 

Today I am trying day 1 of Risperdal so how see how it goes. 

Edited November 14, 2018 by JJ17