Spoke with the gastroenterologist about my trial (ended) with Simalviane and Alflorex+. Simalviane (simeticone and alvarine citrate) does seem to alleviate the functional bloating somewhat but Alflorex+ didn't do much for my IBS C symptoms. I will continue using Simalviane for now.
Also discussed the use of prucalopride for my symptoms. He agreed that I could try this medication for a short while to see if my body/intestines may benefit. I'll start with 1mg in first instance and can increase the dosage to 2mg daily.
It may have some beneficial synergistic effect for my MDD and GAD too, for which I take venlafaxine 187.5mg. Could be that in the end I 'just' have a neurotransmitter dysfunction leading to major depressive disorder, generalised anxiety disorder, pannic attacks and IBS C, amongst others.
Will see, notice, what the effect will be in the near future 🤞🏻
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"Association between a selective 5-HT4 receptor agonist and incidence of major depressive disorder: emulated target trial"
Published online by Cambridge University Press: 07 August 2024
"Background
The serotonin 4 receptor (5-HT4R) is a promising target for the treatment of depression. Highly selective 5-HT4R agonists, such as prucalopride, have antidepressant-like and procognitive effects in preclinical models, but their clinical effects are not yet established.
Aims
To determine whether prucalopride (a 5-HT4R agonist and licensed treatment for constipation) is associated with reduced incidence of depression in individuals with no past history of mental illness, compared with anti-constipation agents with no effect on the central nervous system."
Serotonergic Control of Gastrointestinal Development, Motility, and Inflammation
"Introduction
Although it is most well-known for its roles in central nervous system (CNS) function, serotonin, or 5-hydroxytryptamine (5-HT), was first discovered in the gastrointestinal (GI) tract. Vittorio Erspamer, the pharmacologist who discovered 5-HT, first named it “enteramine” after extracting it from rabbit gastric mucosa in 1937 (67), and later noted that it was present in the GI tract of every vertebrate animal he studied. Ten years later, Maurice Rapport, Arda Green, and Irvine Page identified this molecule as serotonin, named for its origins in serum (“sero”) and its ability to increase tone or vasoconstriction (“tonin”) (189, 190), and published its structure as 5-HT in 1949 (188). This research merged in 1952, when Erspamer confirmed that the enteramine molecule he had discovered in the mucosa of the GI tract was 5-HT (68). 5-HT was then found in the CNS and discovered to have roles in essential functions such as sleep, mood, and appetite (33). Although 5-HT has many important roles in the brain, the vast majority of the body’s 5-HT is produced in the gut, where it participates in functions such as motility, sensation, inflammation, and enteric neurogenesis (28, 74, 92, 158). The roles of 5-HT in these functions are reviewed, as well as its role in the pathophysiology of disorders of gut-brain interaction (DGBIs) and inflammatory bowel diseases (IBD)."
Could the Simalviane be working against the IBS-C, since it is antispasmodic (reduces muscle contractions)?
Would be interested to hear about how you get on with Prucalopride. I take Linaclotide for IBS-C - it helps with the pain but not the BMs for me (though seems to for others) and I have to counteract that with fibre intake. Did you try that one and if so, how did you get on with it?
Had a trial with linaclotide this year too but made me running to the loo so did stop using it. Tried to split capsule in half and this was also suggested by the gastroenterologists last friday.
Maybe if prucalopride doesn't have the desired effect I will give linaclotide another try, as also suggested by the gastroenterologists. But first this new trial with prucalopride for the next four weeks.
Just wondering how long you tried Linaclotide for? I think it had that effect on me initially and then stopped, I carried on with it since it helped with the pain. Good luck with the Prucalopride.
Only for a very short time because of the running to the loo thing. So it didn't get a proper chance from me and with that in mind it maybe deserves another chance if prucalopride should fail.
Hi, regarding Linoclotide - I have to take the lowest dose possible - 72 mcg. When I was prescribed the typical dose of 144 mcg for IBS-C, I had cramps and was running to the loo. 72 mcg works best and even then I sometimes have to skip a day once a week because it can be too much. It has helped me a lot. What dose were you prescribed?
"Unfortunately linaclotide is only available in one dose, 290mcg capsules in the Netherlands. After my consult with a GP and the pharmacist yesterday, I will try to open the capsule and divide the content over smaller capsules so I can start with a somewhat lower dose.
Lower dosages than 290mcg linaclotide (145mcg and 72mcg) for chronic constipation have already been approved by the FDA in the USA."
😊 you might be able to visit and go to a walk in clinic and have it prescribed at the lower dose! It is expensive here - just over $300 for 3 month supply. Luckily I have benefit coverage for it.
Hello xjrs, I've read several times that linoclotide helps with your pain, can you tell me what type of pain you are referring to? I take it and it helps me poop, althouth it's usually diarrea, but it also causes cramps and it anything, worsens pain.
Hi edwangy , Good to hear from you. The pain I was experiencing was referred IBS pain into my mid to lower back. The gastro said I had visceral hypersensitivity. I used to experience the pain from 2am or so onwards overnight whilst lying down. It took me a long time to figure out this was due to IBS. How long have you been on the Linaclotide for? The full pain effects are experienced by 10 weeks. If it is worsening pain and not improving the pain by 10 weeks, you may need to try something else. It is very maddening that some things that help some people, don't always help others, isn't it? For instance, the Linaclotide doesn't seem to help the constipation for me, but it helps the pain and for you it is the other way around. If you've not been on it for very long, it might be worth purservering, since the worsening pain might be your body getting used to it.
I suffer from cronic constipation and be told its SCT. Have tried Prucaopride for 3 months on 2 seperate occasions unfortuneately it did not make any difference at all. I was dissapointed as had high hopes with this medication would help me. It did work for a friend of mine so hopefully you will have better luck
Slow colonic transit. Diagnosed by me swallowing 2 pills/pellets each day for 3 consecutive days. Then 2-3 days later an x-ray to see if still in my colon. Yes all 6 still there
Hi, I have been taking prucalopride for about a year for chronic IBS-C and slow gut transit. Tried linaclotide first, yes it helped the pain but did nothing for bm's. Prucalopride 2mg (max dose) was brilliant at first but bm effects tapered off quite quickly. Consultant also prescribed 2 docusate sodium, increased to 4.
With Prucalopride I feel so much better. It lifted the brain fog, I feel more like my old self, clearer, more grounded, it's also improved my sleep. It's expensive so can only be prescribed by gastro specialists.
I also take 75 mg venlafaxine and Holland & Barrett colon cleanse. I'm very careful with my diet and triggers, also looked at fodmaps too.
Very constipated at the moment 🥴 and don't feel well at all. Need to take bisacodyl again and also macrogol the get rid of the fecal mass in my lower right abdomen, the cecum I guess. This is my problem, it always gets stuck here. So no luck with prucalopride so far. Wrote the gastroenterologists and asked if it isn't slow transit constipation instead of IBS C I suffer from. Have had a transit study in the past but this was flawed, I kept using bisacodyl during the study, in agreement with the hospital however. Waiting for an answer.
I will try prucalopride again, half a tablet. But will it combine now with bisacodyl because my bowel in my right lower abdomen feels better when using bisacodyl, better transit, cleaner intestines in my situation.
Don't know if prucalopride will add some extras but since I already paid for the medication and do have 2 boxes with 28 tablets each, I just thought why not.
Update: really cannot tolerate prucalopride, makes my health worse instead of better. Will no longer take this medication as from the 9th of September.
I'll try to focus on tryptophan instead, start with 150mg once a day. I already take 5-htp 200mg slow release.
I know that I need to be careful because of the antidepressant (venlafaxine) I need to take too. Don't worry, I have much experience with neuropsychiatric drugs for major depressive disorder and generalised anxiety disorder.
Have been taken these, not only venlafaxine, tried many other related drugs in the past, since 2002. Got severely depressed and anxious after a strangulation ileus / volvulus (acute abdomen). All started with a dysfunctional bowel.
Have been in touch with the gastroenterologist discussing my first experience with prucalopride.
He wrote me that I really should try it again, despite the side effects I experienced in first instance. He also wrote that they prescribe the same medication for Slow Transit Constipation (STC), I have been diagnosed with IBS C.
I wrote him I will try this medication again as from this Sunday. I will also try to take it a bit longer than the first time.
Don't think it will make a difference this time but at least I can give it another try, to be totally sure that it's because of the side effects that I can't take this medication, or can I 🤔🤞🏻
If not, I will ask my GP for a referral to a gastroenterologist in my region to discuss the fact that in my opinion I should have a new whole gut transit test because the first transit test was flawed. I kept using bisacodyl during the test. I contacted the radiology team of the University hospital that I couldn't do the test without also taking bisacodyl and they told me I could continue using bisacodyl during the test. So that is why I think it still could be STC, a (local, the proximal colon/cecum) neuromuscular disorder, instead of IBS C, or even a local "pseudo obstruction" although I've been told that the latter isn't the case in my situation. But without a proper, objective whole gut transit study and maybe even a manometry of the proximal part of the colon, who can tell for certain this wouldn't be the case?
I took a half tablet, approximately 1mg, prucalopride (Resolor) Sunday in the late afternoon. The result, I have been lying on my couch for merely the whole next day feeling sick. Also needed to take bisacodyl as rescue medication. So did try to find some more information on the adverse effects of prucalopride / warnings issued when not to use this medicine. I found the following information from the manufacturer in the United States:
"Do not take Motegrity (prucalopride )if you:
are allergic to Motegrity. Allergic reaction symptoms may include trouble breathing, rash, itching and swelling of your face, lips, tongue or throat.
have a tear in your stomach or intestinal wall (bowel perforation), a bowel blockage (intestinal obstruction) or serious conditions of the intestinal wall such as Crohn’s disease, ulcerative colitis.
Before taking Motegrity, tell your healthcare provider (HCP) about all of your medical conditions, including if you:
have or have had depression, suicidal thoughts or actions, or mood problems.
have kidney problems. Your HCP may give you a lower dose of Motegrity.
are pregnant or plan to become pregnant. It is not known if Motegrity will harm your unborn baby.
are breastfeeding or plan to breastfeed. Prucalopride can pass into your breastmilk. Talk with your HCP about the best way to feed your baby if you take Motegrity.
Tell your HCP about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
What are the possible side effects of Motegrity?
Motegrity may cause serious side effects, including:
unusual changes in mood or behavior, thoughts of hurting yourself, trying to hurt yourself, or suicide. Stop taking Motegrity right away and tell your HCP immediately if your depression gets worse, you feel sad, hopeless or begin to have thoughts of suicide, thoughts of hurting yourself or you have tried to hurt yourself or if you develop new depression.
The most common side effects of Motegrity include:
headache
stomach area (abdominal) pain or bloating
nausea
diarrhea
dizziness
vomiting
gas
fatigue
These are not all the possible side effects of Motegrity. Call your doctor for medical advice about side effects.
You are encouraged to report negative side effects of prescription drugs to the FDA.
Motegrity is a prescription medicine used in adults to treat a type of constipation called chronic idiopathic constipation (CIC). Idiopathic means the cause of the constipation is unknown. It is not known if Motegrity is safe and effective in children."
So is it a side effect I suffer from or is it an "allergic reaction" or do I have a not yet recognised/undiagnosed serious problem with the functioning of a part of my gut wall??
I didn't take this medicine on Monday evening and will try a quarter tablet (0.5mg) on Tuesday afternoon.
In the 6 clinical trials described above, 5% of patients treated with 2 mg of MOTEGRITY once daily discontinued due to adverse reactions, compared to 3% of patients in the placebo group. The most common adverse reactions leading to discontinuation were nausea (2% MOTEGRITY, 1% placebo), headache (1% MOTEGRITY, 1% placebo), diarrhea (1% MOTEGRITY, <1% placebo), or abdominal pain (1% MOTEGRITY, 1% placebo)."
I'll wait a bit longer with taking prucalopride again. When I will take it again I'll start with a quarter tablet, approximately 0.5mg because of the adverse reaction I experienced.
I will continue with my trial supplementing L-tryptophan. My overall health seems to be a bit less worse since I started taking a low dosage L-tryptophan.
I'm gradually increasing the dosage to find out how much it affects the functioning of my gastrointestinal tract and, as a result, my overall health and wellbeing. (healthunlocked.com/theibsne...
As from the 21st of October I started taking prucalopride again, approx 0.5mg a day this time. Hopefully with less adverse effects/side effects this time, because of the lower dosage 🤞🏻
Noticed once daily 0.5mg prucalopride is too less for my IBS C symptoms so started taking 0.5mg twice a day instead. Didn't notice any side effects after taking 0.5mg so that's a good thing. By the way, I stopped using bisacodyl. Only will use it as rescue medication.
Needed to take bisacodyl too because of the fact that I haven't been able to have defecation for 3 days and that's not normal for me. Now trying to analyse why. Could be related to an increased fat intake, eating 🐐 🧀 since a week so stopped eating goat cheese. Experience from the past is that increased fat and fibre intake will worsen my IBS C symptoms so it could be related.
Did increase the dosage prucalopride, have taken the maximum of 2mg this morning. However I did split the tablet in 4 parts and did put them in empty 💊. Took two capsules around 6 AM and did take the second two capsules around 9 AM. Feel that it does work but the initial dose was too little for my symptoms, constipation. Now wait and feel what's happening in my bowels, if 2mg will work for me 🤞🏻. I may take a little bisacodyl in the beginning if necessary. If prucalopride won't work for me, after I tried long enough, I may need to switch to another type of medication for my IBS C symptoms, maybe need to try linaclotide again. But this drug caused diarrhea when I did try it before so not so sure if it's a better option for me.
"Not everyone responds to treatment straight away so it is important that you continue
taking Prucalopride for the full 4 week course.
If you do not respond to Prucalopride at first you may need to use another laxative
as ‘rescue’ medication. Your health professional will be able to advise you further"
So I need to be patient and use rescue medication if I feel it's necessary. Rescue medication could be bisacodyl, cascara sagrada, Triphala, senna. Although I can't use senna because I had some adverse reactions, it's a histamine releaser if I recollect correctly, causing inflamation.
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