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In 2003 I discontinued the anti-psychotic drug Risperdal. A month later I developed severe, classic IBS-C, and suffered with the condition for over six years. Last year I began taking Risperdal again, and within a few months the symptoms of IBS completely vanished. Bowel movements were regular and complete, there was no more intense, incapacitating rectal pain. My life returned to exactly how it had been for the first twenty-three years of my life, before I developed IBS. The illness was cured and I was once again a "normal" person who had the capacity for work and social relationships.Now, the catch is that Risperdal entails undesirable side-effects, like cognitive and emotional blunting. There is also risk of more severe neurological effects developing. For these reasons I'd love to be off the drug. Precisely when I lower the dose from 1.0mg to 0.75mg, however, the symptoms of IBS begin to re-appear. In the name of finding a different drug that, while also curing IBS, would not have the side-effects of an anti-psychotic, I'm curious as to the pharmacological role of serotonin in IBS. According to Wikipedia, Risperdal"belongs to a class of antipsychotic drugs known as atypical antipsychotics that have more pronounced serotonin antagonism than dopamine antagonism [...] It has actions at several 5-HT (serotonin) receptor subtypes. These are 5-HT2C, linked to weight gain, 5-HT2A, linked to its antipsychotic action". I'm curious in particular about the fact that my experience seems to be in direct contradiction with the paradigm according to which IBS is usually thought about and treated. Typically, serotonin agonists, not antagonists, are utilized in the treatment of IBS-C. Zelnorm, for example, is a serotonin agonist. Although I'm not sure about this, I believe all SSRIS are serotonin agonists as well. On the other hand, drugs used for IBS-D, such as Lotronex, are considered serotonin antagonists. Thus I cannot figure out why a serotonin antagonist like Risperdal would cure my IBS-C, while serotonin agonists like Zelnorm and SSRIs did nothing for me. Although these questions are very difficult and for the most part far beyond me, perhaps there is someone out there who can help me make sense of this apparent contradiction, as well as suggest some pharmacological possibilities.My wish is also to simply let people know that I did find a cure; something which for six years seemed to be an impossibility.
 

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It isn't just agonist/antagonist but which of the serotonin receptors the drugs effect as well.I do not know which receptor your drug actually works on. Zelnom may effect receptors in a different way than Lotronex but it also effects the 4th one of the serotonin receptors and Lotronex effects the 3rd on. SSRI's mostly effect yet another one of the serotonin receptors.Additionally there are idiosyncratic reactions. SSRI's may tend to cause diarrhea more than constiaption, but they also cause constipation for some people in clinical trials. It isn't all one or all the other. There is some of both for most of the psychiatric drugs.Off to look yours up and see if I see anything that makes sense.From the clinical trial data on rxlist.com looks like it causes diarrhea a bit more often than it causes constipation (like 8% vs 6%)
 

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Discussion Starter · #3 ·
Wikipedia says Risperdal has actions at 5-HT2C and 5-HT2A receptors....I don't think the drug cured my IBS-C simply by inducing a diarrhea side-effect. I experienced no diarrhea-like symptoms. What I did experience was a complete normalization of peristalsis and evacuation, as well as an almost total reduction of that tormenting rectal sensation which was a primary component of my IBS-C. In other words, in my opinion Risperdal did not work by superficially countering constipation with diarrhea. Rather, it seemed somehow to target the essence of IBS-C pathology. Along what pathways it did so is the massive mystery I'm now in the process of trying to solve.
 

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The antidepressants also work besides by changing movement through the GI tract (which is what Lotronex and Zelnorm do to ease diarrhea and constipation) they can also effect the excessive sensing of the GI tract which leads to it over reacting to things or blocking inappropriate pain. Zelnorm and Lotronex do both of those.So even SSRI's tend to cause diarrhea more than constipation they also effect pain and other sensory issues. I don't know that your drug must do something completely and totally different than every other serotonin effecting drug.A lot of people take Zelnorm, Lotronex, SSRIs and every other kind of antidepressant to deal with pain and rectal hypersensitivity that happen with IBS no matter what kind of stooling issues you have. However one that tends to loosen stools is better for those that tend to be constipated and those that tend to constipate are better for those with diarreha but all of them seem to work on rectal hypersensitivity issues. I would suspect your drug does too. Doesn't seem logical it can't be doing that for some people when every last other drug effecting serotonin seems to help with pain and rectal hypersensitivity issues for other people.Usually if you add a drug that tends to cause a bit of diarrhea to someone that is constantly constipated they go to normal (assuming the dose is right) not go all the way to watery diarrhea.
 

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I don't know that your drug must do something completely and totally different than every other serotonin effecting drug.
Risperdal did do something different. Unlike Zelnorm and the several SSRIs with which I experimented over the years, it completely eliminated IBS. Perhaps other sufferers have found relief in SSRIs or Zelnorm. Reading this forum, however, I've come across little evidence of anyone finding total satisfaction with those drugs. I simply mean to bring attention to the fact that the atypical antipsychotic Risperdal, which apparently has antagonistic actions at 5-HT2C and 5-HT2A receptors, made my IBS-C disappear.
 

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I don't know with the side effect profile if they will prescribe it for people who don't need it for mental health reasons. Usually the more severe the mental illness the more risk they will take with side effects. Not sure how it overall compares to the antidepressants for risk in healthy people.I got really good relief of the rectal hypersensitivity and pain (better when the IBS was milder than when it was severe, but it was enough to keep me functional even if I wasn't 100%) with Buspar which is pretty low risk for non-anxious people to take. Other than a bit of light-headeness right after the dose most people don't have much in the way of side effects and I could counter act the light-headedness that was only for a short while if I made sure I ate before I took it in the morning.However I am glad to hear it is working well for you. I don't know if it caused the IBS-C or you got it while you were on the drug from something else and it was treating those symptoms so they didn't show up until after it was discontinued.
 

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Discussion Starter · #7 ·
I think atypical antipsychotics generally affect the body and mind much more profoundly than most antidepressants. This, however, doesn't stop doctors from prescribing them unrestrainedly. In current mental health practice you don't need a schizophrenia diagnosis in order to be considered a legitimate candidate for these drugs. An anxiety disorder or refractory depression will suffice. This leads me to believe that the atypicals could easily become standard off-label treatments for IBS. Personally, the rewards of living free of IBS outweigh the risks and side-effects associated with the Risperdal; although only by the slimmest of margins.
 

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I think atypical antipsychotics generally affect the body and mind much more profoundly than most antidepressants. This, however, doesn't stop doctors from prescribing them unrestrainedly. In current mental health practice you don't need a schizophrenia diagnosis in order to be considered a legitimate candidate for these drugs. An anxiety disorder or refractory depression will suffice. This leads me to believe that the atypicals could easily become standard off-label treatments for IBS. Personally, the rewards of living free of IBS outweigh the risks and side-effects associated with the Risperdal; although only by the slimmest of margins.
Not sure I can agree with you there. I tried taking a SSRI to treat my IBS and the side effects were god awful to deal with. I'd rather feel normal (state of mind) and have IBS then be all looped up on these drugs. There are many people on these forums with alot of problems and they should be on these things but the rest of us just want to treat our IBS and not our heads.I don't agree with the way these meds are being used to treat IBS. I know for a fact that when i took those SSRI's it may have slightly helped my IBS but my body and head where saying "what the heck are you taking these for" and by no means did it cure me. I think it gives IBS patients a bad rep and gives doctors a excuse to simply say they're all a bunch of whacko's that have psycho problem's.Not for me but to each his own.
 

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Discussion Starter · #9 ·
I see what you're saying. It would be great if you discovered a cure outside of the serotoninergic paradigm, since then psychotropic medications and the accompanying stigma could be altogether eliminated from the theory and practice of IBS treatment. Until that happens, though, I'll just have to put up with being cured by this 5-HT2C and 5-HT2A receptor antagonist. On that note, anyone have any thoughts on the drug Mirtazapine in this context?
 

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Could this all be linked to physiological factors?Is it possible Ilya that you have something like Pevlic Floor Dysfunction.I have been diagnosed with this. My muscles dont co-ordinate properly... for some reason my brain 'turned off' my ability to pass stools effectively. Perhaps the anti-depressant/medication counteracts this switch in the brain.....??
 

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There are serotonin receptors all over the body and most of the serotonin in the nervous system is in the gut, not the brain.Because serotonin effecting drugs are used a lot in psychiatry a lot of people think all the serotonin is in the brain, but the body uses it for a lot of things, and a lot of those are in the gut nerves. It takes a lot of nerves to keep the GI tract running properly so that is why a lot of the serotonin in the body is in the gut.They usually think the serotonin effecting drugs both specifically for IBS and any antidepressants, etc used are directly effecting the gut nerves.
 

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It may sound counter-intuitive, but I'm highly suspicious Remeron could also be a cure for IBS-C. Remeron is the only antidepressant that, like the antipsychotic Risperdal, is an antagonist at 5-HT2C and 5-HT2A receptors. Now I need to find a doctor who will write me a prescription so I can conduct an experiment.
 

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Remoren usually is used for IBS-D not IBS-C.It is similar chemically to the drug Lotronex. When Lotronex was pulled this drug and Zofran which is an anti-nausea drug were common things people tried.In studies it is more likely to cause constipation as a side effect then diarrhea.
 

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ILYA - this is very interesting as I have just been prescribed an atypical antipsychotic. The doctor explained to me that whilst I am not depressed or anxious the drug is a tranquliser that might just calm everything down and make the digestive system start working normally again. He also prescribed the anti-depressant Mirtazapine in a low to medium dose with the same thinking in mind.I should say that I am not a 'typical' IBS patient as I am not constipated and do not have diarrhea. I have almost constant nausea and stomach discomfort.In reading your story may I ask how long you have were on Risperdal for? And is it not possible that it didn't actually give you IBS but that it either just started anyway due to coincidence or that you got it when you were on Risperdal but it was just kept at bay by that drug? I also think it is fair to say that the pain you describe in your rectal area doesn't sound like typical IBS and as one other user mentioned could be a pelvic floor problem.Thanks for posting. I look forward to your answers.
 

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The doctor explained to me that whilst I am not depressed or anxious the drug is a tranquliser that might just calm everything down and make the digestive system start working normally again. He also prescribed the anti-depressant Mirtazapine in a low to medium dose with the same thinking in mind.
I really think these drugs, atypicals and the novel antidepressant Mirtazapine, do something far more specific than just "calm everything down" with a general tranquilizing effect. I think it is their particular serotoninergic action. With Risperdal and Mirtazapine/Remeron, this is an antagonistic action at 5-HT2c and 5-HT2a receptors. I don't know how other atypicals, Zyprexa or Seroquel for instance, affect serotonin. I do believe Risperdal has a much more pronounced serotoninergic effect than the other atypicals. I find comparing our situations tricky, however, since your issue is not with IBS-C but nausea and stomach discomfort. I do know that all literature suggests Mirtazapine is excellent for nausea. It is a serotonin antagonist, and other drugs of this class are apparently used to treat nausea from chemotherapy (someone correct me if I'm wrong) The drug Lotronex, used to treat IBS-D, is also a drug of this class. Now, what I'm wrestling with right now is that the atypical Risperdal, another serotonin agonist like Mirtazapine and Lotronex, has at the precise dose of 1.0mg cured my IBS-C. At the risk of making a grandiose statement, I'm seriously wondering if IBS scientific inquiry has perhaps overlooked serotonin antagonists as a treatment for IBS-C, while focusing too much attention on serotonin agonists like Zelnorm and SSRI antidepressants. Of course, this part doesn't really apply to you, idkwia, since you don't have IBS-C. Anyway, I hope what I'm saying here is at least partly intelligible.
In reading your story may I ask how long you have were on Risperdal for? And is it not possible that it didn't actually give you IBS but that it either just started anyway due to coincidence or that you got it when you were on Risperdal but it was just kept at bay by that drug?
As far as my experience with Risperdal, I was on it the first time for two years, from 2001 to 2003. While it could have been a coincidence, my suspicion is still that my IBS-C developed as a result of the drug powerfully messing around with HT2c and 5-HT2a receptors. Along these pathways, I think I became physiologically dependent on the drug for normal bowel function. Thus, when I discontinued the med the IBS-C emerged. After many years of suffering, I went back on Risperdal just over a year ago and the symptoms vanished. Now, of course, the goal is to find out if Mirtazapine, which has almost exactly the serotoninergic profile of Risperdal, can cure the IBS-C, thus allowing me to be free of atypical antipsychotics. (I don't want to worry you idkwia, since they aren't the worst thing in world in terms of side-effects. However, if you can find a way to get by and achieve what you want in life without antipsychotics, that's probably the way to go)
 

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Discussion Starter · #16 ·
hmmm....Trazodone is also a 5-HT2c and 5-HT2a antagonist, with possibly fewer side-effects than Remeron. Bring on the trazodone then...
 

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ILYA - thanks a lot for your reply. I am going to see what happens when I increase the Mirtazapine to 30mg from 15mg and then think about the atypical psychotic which is Olanzapine 2.5mg per day.With regard to my comment of these drugs calming averything down, this was just the doctors way of making things simple for me to understand I am sure. But overall the gut and the brain may be overacting to normal digestion and so his explanation makes sense and worth a try.
hmmm....Trazodone is also a 5-HT2c and 5-HT2a antagonist, with possibly fewer side-effects than Remeron. Bring on the trazodone then...
I should tell you that I didn't experience any side effects with Mirtazapine. In addition I have just read that one of the side effects of Trazodone is constipation.Either way, good luck and let us know how it goes.
 

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In addition I have just read that one of the side effects of Trazodone is constipation.
Constipation is also a listed side-effect of Risperdal. Furthermore I have read reports of people experiencing terrible constipation on Risperdal. Yet Risperdal cures my IBS-C. At any rate, this pharmacology, meaning the significance and function of the many 5-HT receptors (http://en.wikipedia.org/wiki/5-HT_receptor) in relation to agonist or antagonist drugs, is very, very complicated business. From a layperson's perspective theorizing as I'm trying to do is frustrating and probably useless. For instance, I deduce from my experience with Risperdal that all 5-HT2c and 5-HT2a antagonists could cure IBS-C; and then I discover that Elavil, a drug which I know from experience does nothing for my IBS, is also a 5-HT2c and 5-HT2a antagonist. So my Remeron/Trazodone hypothesis has taken a bit of a hit. Personal experimentation is the only way to go. Once I resolve my currently disastrous doctor situation, I will definitely let people know what I find out regarding how Remeron and Tradozone compare to Risperdal in terms of curing IBS-C.
 

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this has been a fascinating thread. thanks for starting it, ilya.i have ibs-c. i take 75 mg tradozone nightly for my insomnia--have been taking it for at least five years. at first i was concerned about taking it because constipation is listed as one of the side effects but it hasn't seemed to have made my c worse. it definitely hasn't helped my c either--but i'm taking a fairly low dosage. it does help me sleep.
 

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Discussion Starter · #20 ·
ok...I just stumbled upon some facts that seem to support an entirely different theory of Risperdal's serotonergic role in causing and curing my IBS-C.As well as a 5-HT2c and 5-HT2a antagonist, Risperdal is a 5-HT7 "inactivating antagonist" (http://molpharm.aspetjournals.org/content/70/4/1264) (http://en.wikipedia.org/wiki/5-HT7). While 5-HT2c and 5-HT2a receptors have considerable roles in GI functioning, I have found a study (http://www.cmj.org/periodical/PaperList.asp?id=LW2007123398611009282) which speculates that 5-HT7 receptors also play a very important, perhaps essential part in the pathology of IBS:"5-HT7R, a G-protein-coupling receptor, has been recently shown to have at least 4 subtypes1 and plays a role in regulating smooth muscle relaxation in the gastrointestinal and peripheral nociceptive pathways. 5-HT7R may be involved in the pathological mechanisms of gastrointestinal dyskinesia, abdominal pain and visceral paresthesia in IBS"Here is one conclusion of the study: "This finding further indicates that the 5-HT7 receptor's increasing expression in the gut closely correlates with mechanisms such as gastrointestinal dyskinesis of IBS-C. Further studies on the 5-HT7 receptor's role in IBS patients would provide new insights into the pathogenesis of the disease and 5-HT7 receptor ligands may offer innovative opportunities for the pharmacological treatment of functional bowel disorders such as IBS."Thus, Risperdal is an irreversible inactivating antagonist at a receptor potentially central to all the worst symptoms of IBS. Very interesting; although I don't like the sound of this at all. Risperdal is the only anti-psychotic, and one of only a handful of other medications, which possesses this strange property of being an irreversible inactivating antagonist of the 5-HT7 receptor. So, there's a chance I could be stuck on it the rest of my life. Nightmares like this are what happens when companies market and doctors prescribe drugs the pharmacological mechanisms of which are almost totally unknown. At any rate, the point to be found in all this for other IBS sufferers could be that 5-HT7 is where it's at when it comes to IBS. I realize, again, that these issues are far too complicated for this board. At least I think they are. Maybe someone is out there who has some insight. I just feel compelled to post because I believe my apparently unique experience with Risperdal is a potentially fertile source of speculation about IBS. That speculation would of course need to be pursued by a team of pharmacologists and IBS specialists. Here my primary hope is to simply stumble upon some ideas regarding already approved medications that would mimic the action of Risperdal, thus introducing other options for curing my IBS, and possibly that of others as well.
 
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