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JJ17

Zyprexa vs Risperdal for OCD

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8 hours ago, JJ17 said:

Added 150mg Wellbutrin and it’s only been roughly a week and already noticed more talkative/motivated/etc. But I also have increased anxiety (nothing too bad) and sometimes upset stomach. This is the ONLY antidepressant that I felt side effects from at a standard dose (even if mild) but at the same time it seems like mild side effects means the medicine is working, at least for me. 

You may notice that some of the anxiety goes away after 2-3 weeks. Feeling more talkative and motivated is exactly what I would expect after a week of 150mg bupropion. It works pretty quickly relative to it serotonergic counterparts.

8 hours ago, JJ17 said:

As I have the same “issue” with SSRIS. I had no side effects from: Paxil, lexapro, Prozac, or Zoloft at normal doses - and no positive changes either - so it felt like I was “taking nothing”. It wasn’t until I went to the max or higher dosage (40mg-60mg  Paxil, 200mg Zoloft) that I felt minor side effects, but also at the same time felt some benefit from the medicine. Maybe some minor side effects are a sign they are working (at least for me) ? I think my brain is so used to so many medicines that it takes high doses to even affect me, both side effect wise and benefit wise. 

You may have several long allele repeats for the SERT. This would mean that you have more of the serotonin transporter than most, which would mean that your brain more readily clears serotonin from the synapse on its own requiring much higher doses of SSRIs to have an effect. I by contrast have 3-4 short allele repeats, which means I am an under-producer of the serotonin transporter protein. As would be expected, I don't need very high doses of serotonergic antidepressants to have an effect. I currently float on Trintellix between 10mg and 15mg. At 10mg, SERT occupancy from Trintellix is only like 50-60%, which by the books isn't nearly high enough of an occupancy to have an antidepressant effect, but for me it does.

8 hours ago, JJ17 said:

As far as Risperidone and OCD, what method of action is believed to help OCD? At 0.5 mg to 1mg it’s “weak” in terms of D2 dopamine blocking. It isn’t until 2mg that it supposedly reaches the D2 occupancy needed for antipsychotic effects. BUT I don’t know if that matters when using it to try and treat OCD. Is higher D2 occupancy from Risperidone a good or bad thing for Obessive thoughts? Since I don’t feel anything from taking 1mg maybe I need to up the dose? 

 

7 hours ago, HydroCat said:

AFAIK it is unclear which mechanism actually causes intrusive thoughts.

Yeah this is pretty much the case. It certainly has something to do with both serotonin and dopamine but I'm not sure they fully understand why quetiapine and risperidone work in treatment-resistant cases. 

7 hours ago, HydroCat said:

Again, only from my personal experience, Amisulpride (a pure D2/D3 antagonist) was useless for my intrusive thoughts, while both Risperidone and Abilify (D2/D3+5HT2A antagonists) were pretty good.

So a higher dose may do the trick, not only because of D2 occupancy.

Besides that, a low dose will have more antagonist action on presynaptic D2 receptors and as the dose goes up it gradually occupies postsynaptic D2 too. I am not sure if that is a good or a bad thing though, never went past the 1mg.

This is also a very good point. When you look at affinities, if the affinity for both D2S (pre-synaptic) and D2L (post-synaptic) are available, you can determine if there is a higher affinity for pre-synaptic receptors at lower doses. Quetiapine and risperidone both do this, and so does amisulpride. However, antagonism of D2S would actually increase dopamine release and without post-synaptic antagonism, this would actually result in dopamine activation. So it's possible that they mediate their effects in OCD by balancing dopamine signaling a bit. But even that's confusing to say because the gold standard for OCD is clomipramine which has a super high affinity for SERT and would theoretically ramp up serotonin activity to a point that dopamine signaling is heavily suppressed downstream. So I suppose some normal dopamine signaling is still necessary even with 80-90% occupancy of the SERT by clomipramine. So low-dose AAP with higher affinity for pre-synaptic receptors could make sense for some people.

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On 3/28/2019 at 2:31 AM, Catwoman said:

This sounds familiar to me. Although from SSRI's I did have a lot of effect in the first 5 years, but side effect wise I just had restless legs and vivid dreams (with higher dosages). It didn't really feel like I was on medication and I could even miss a few pills without getting into trouble. 
Some people get side effects from 5-10 mg's of Lexapro but I needed 20 mg in order for it to work.

With risperidone it also feels like "I take nothing", only the first day it made me sleepy because I took it in the morning instead of before bed. 
But I haven't been on it that long (just over a week), so I can't tell if I will have any benefit. If it does kick in it would be the ideal med for me: better sleep, a clearer mind during the day and no troubling side effects. 

Are you still taking Risperidone? If so any update if it’s working? I’m debating trying it twice daily (once in morning and once at night) as I wonder if by the time I wake up a lot of it’s effects maybe have worn off. 

On 3/28/2019 at 1:24 AM, HydroCat said:

AFAIK it is unclear which mechanism actually causes intrusive thoughts.

Again, only from my personal experience, Amisulpride (a pure D2/D3 antagonist) was useless for my intrusive thoughts, while both Risperidone and Abilify (D2/D3+5HT2A antagonists) were pretty good.

So a higher dose may do the trick, not only because of D2 occupancy.

Besides that, a low dose will have more antagonist action on presynaptic D2 receptors and as the dose goes up it gradually occupies postsynaptic D2 too. I am not sure if that is a good or a bad thing though, never went past the 1mg.

I felt like 2mg was blocking “too much dopamine” as it seemed to weaken my ADHD med Ritalin quite significantly. Ritalin helps with energy/focus/motivation/attention/etc for me, but if I increased the Risperidone dosage it would weaken those Ritalin effects. So I went back down to 1mg only. 

 

Does anyone think it would be a good idea to take Risperidone twice daily? I have read some people take it twice daily, once in morning and once at night. Although I’m not sure if those people are doing it for its antipsychotic effect or for off-label use like OCD. But I still wonder if maybe taking it during the day might “calm the mind” so to speak, which in turn maybe would help OCD? I know day time sedation could be an issue but should go away with time.  I might try this, just wondering if anyone else had experience with once daily dosing vs twice daily. 

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Also found this on drugbank website that explains how Risperidone works:

 

The primary action of risperidone is to decrease dopaminergic and serotonergic pathway activity in the brain, therefore decreasing symptoms of schizophrenia and mood disorders [3411].

Risperidone has high affinity binding to serotonergic 5-HT2A receptors versus dopaminergic D2 receptors in the brain [23]. Risperidone binds the D2 receptors with lower affinity than the traditional, first generation antipsychotic drugs, which bind with very high affinity. A reduction in extrapyramidal symptoms in Risperidone use is attributed to its moderate affinity for dopaminergic D2 receptors [7115].

Mechanism of action
Though its mechanism of action is not fully understood at this time, current focus is on the ability of risperidone to inhibit the D2 dopaminergic receptors and 5-HT2A serotonergic receptors in the brain. Schizophrenia is thought to be caused by an excess of dopaminergic D2 and serotonergic 5-HT2A activity, resulting in overactivity of central mesolimbic pathways and mesocortical pathways, respectively [345]
D2 dopaminergic receptors are transiently inhibited by risperidone, reducing dopaminergic neurotransmission, therefore decreasing positive symptoms of schizophrenia, such as delusions and hallucinations. Risperidone binds transiently and with loose affinity to the dopaminergic D2 receptor, with an ideal receptor occupancy of 60-70% for optimal effect [710]. Rapid dissociation of risperidone from the D2 receptors contributes to decreased risk of extrapyramidal symptoms (EPS), which occur with permanent and high occupancy blockade of D2 dopaminergic receptors [67]. Low affinity binding and rapid dissociation from the D2 receptor distinguish risperidone from the traditional antipsychotic drugs. A higher occupancy rate of D2 receptors is said to increase the risk of extrapyramidal symptoms and is therefore to be avoided [678]
Increased serotonergic mesocortical activity in schizophrenia results in negative symptoms, such as depression and decreased motivation [1112]. The high affinity binding of risperidone to 5-HT2A receptors leads to a decrease in serotonergic activity. In addition, 5-HT2A receptor blockade results in decreased risk of extrapyramidal symptoms, likely by increasing dopamine release from the frontal cortex, and not the nigrostriatal tract. Dopamine level is
therefore not completely inhibited [57]. Through the above mechanisms, both serotonergic and D2 blockade by risperidone are thought to synergistically work to decrease the risk of extrapyramidal symptoms. 
Risperidone has also been said to be an antagonist of alpha-1 (α1) alpha-2 (α2) receptors, and histamine (H1) receptors [11]. Blockade of these receptors is thought to improve symptoms of schizophrenia, however the exact mechanism of action on these receptors is not fully understood at this time [1112].
https://www.drugbank.ca/drugs/DB00734
Good read and matches what many of you have said, such as while it does generally decrease dopamine activity it increases dopamine release in some areas. 
 

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On 4/6/2019 at 12:51 PM, JJ17 said:

Are you still taking Risperidone? If so any update if it’s working? I’m debating trying it twice daily (once in morning and once at night) as I wonder if by the time I wake up a lot of it’s effects maybe have worn off. 

I felt like 2mg was blocking “too much dopamine” as it seemed to weaken my ADHD med Ritalin quite significantly. Ritalin helps with energy/focus/motivation/attention/etc for me, but if I increased the Risperidone dosage it would weaken those Ritalin effects. So I went back down to 1mg only. 

 

Does anyone think it would be a good idea to take Risperidone twice daily? I have read some people take it twice daily, once in morning and once at night. Although I’m not sure if those people are doing it for its antipsychotic effect or for off-label use like OCD. But I still wonder if maybe taking it during the day might “calm the mind” so to speak, which in turn maybe would help OCD? I know day time sedation could be an issue but should go away with time.  I might try this, just wondering if anyone else had experience with once daily dosing vs twice daily. 

When I was on Risperidone I took it at night and it kept me calm the day after.

It has a long elimination half life of 20 hours.

Low dose may actually boost Dopamine activity by antagonising presynaptic D2.

2mg is a moderate dose, your feeling that it blocks too much Dopamine makes total sense.

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On 4/6/2019 at 11:51 AM, JJ17 said:

Are you still taking Risperidone? If so any update if it’s working? I’m debating trying it twice daily (once in morning and once at night) as I wonder if by the time I wake up a lot of it’s effects maybe have worn off. . 

Yes, still taking it. I'm in my third week of taking it and feeling a little calmer than before. I think it's helping a little with my intrusive thought, but in the past I had better days and weeks without risperidone so it could be a coincidence.  I take it before bed; when I do wake up from a very deep sleep  my head feels  really heavy.

I wonder what a dose of 1 mg will be like....will my head feel even heavier when I wake up in the middle of the night? Maybe I won't even wake-up....(which would  be kinda nice)
If the first is the case then maybe taking 0.5 in the morning and taking 0.5 mg at night could help.

I'm not sure if I have to increase to 1 mg anyway, but I am curious of risperidone turns out to be the drug I have been looking for.
 

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