VIDEO: Treatment options for patients with IBS-C, CIC

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So we know that constipation, chronic idiopathic constipation and IBS with constipation exist in a continuum. That's been shown and well-described from the Rome criteria from 2016. There's a nice graph showing the continuum. The major differences would be the severity of abdominal pain. So the more severe and chronic the pain is, the more it tends towards being IBS. It's not that patients with CIC don't have abdominal pain because that's been shown that they do, but the pain is generally less severe.

Interestingly, when you look at the differences between IBS-C and CIC based on patient-related symptoms, the IBS-C patients actually have worse constipation-related symptoms, or worse bowel-related symptoms, than the patients with CIC. In fact, almost all of their symptoms are higher in patients with IBS-C than CIC, except again, particularly abdominal pain, which is the major driver in the requirement to make the diagnosis of IBS-C.

So thinking about it as a continuum, the treatments that we give will overlap as well. So if we first approach the CIC literature and the guidelines which are published simultaneously both in the Red Journal as well as in Gastroenterology in the upcoming, I think, next month, you'll see that the guidelines indicate that first for CIC, that we try standard therapies which are over-the-counter, well-tolerated and relatively inexpensive.

So they may not be the most effective therapy but it does make sense to first try these. And these would include the osmotic laxatives and the osmotic laxative category includes polyethylene glycol, but also includes the magnesium-based treatments. And of course fiber should be considered as well, understanding that fiber may not be effective in all patients. And particularly studies have shown that in patients with pelvic floor dysfunction or slow transit constipation, that fiber may not be very effective and sometimes can make their symptoms worse, particularly bloating. But in the patients with normal transit constipation that's where the biggest overlap with IBS occurs. There you may see some improvement and the combination of an osmotic and a fiber may be the way to go.

Now, as a gastroenterologist, your patients may have already tried those therapies and I think one of our jobs is to make sure they've given it an adequate trial. And oftentimes I'll go back and have them try it again but then add something more, particularly the more severe patients. So once we've gone past the fiber and the osmotic laxatives, then it's time to think about the stimulant laxatives. And the one that's most commonly used is the senna-based therapies. Those can be generally well-tolerated. They can have cramps. But generally senna plus bisacodyl, bisacodyl will be a little bit stronger of a stimulant laxative, tend to be used as sort of rescue therapy, not as frequently used as a chronic, daily therapy. But they're good medications to use in patients, particularly, again, if they feel like they're running into a little bit of trouble. I tend to use the senna because it's better tolerated than bisacodyl, then tend to go to two or four senna a day as needed or add a bisacodyl tablet.

Beyond that, we would go then go to prescription medications. The prescription medications can include the secretagogues, drugs that increase secretions in the GI tract, and the prokinetic drugs that increase peristalsis to occur within the GI tract. So within the secretagogues, the first drug that was approved in early 2010s is lubiprostone and that is medication that opens up the chloride type two channel, that increases chloride. Subsequently, linaclotide, which opens up the CFTR, another chloride channel, and then plecanatide was approved and then the prokinetic drug was approved as well. So we have four FDA-approved medications for chronic idiopathic constipation. All of them are generally well-tolerated, with a major side effect being diarrhea for almost all of the therapies. Lubiprostone at the dose that's used for chronic idiopathic constipation can be associated with nausea, usually short-term, that can occur in up to 30% of people so it's generally recommended you take medication with food. Linaclotide's FDA-approved at three different doses, two doses for chronic idiopathic constipation, the 72 and 145 microgram. The higher dose, the 290, which we'll talk about in a few minutes, is for the IBS-C patients that has the FDA-approval for it. And then plecanatide, approved at one dose for chronically idiopathic constipation and IBS with constipation. And then of course, prokinetic, approved that two doses, but generally use two milligrams once a day for the prokinetic medication.

So that sort of spans the medications. Now, when will you use one vs. the other? Well, that will depend. It depends on your comfort level, what’s FDA-approved. We know from network meta-analyses that they're all going to be effective at treating the symptoms. Again, the mechanism of actions are slightly different for the medications, but they all will improve bowel function. At times we'll even add medications together. So not usually two secretagogues, but we may add like a stimulant laxative plus a secretagogue or a prokinetic drug, such as prucalopride, that will add to an osmotic agent. So you can combine them particularly in the severe patients.

Now, moving on to the IBS-C category, there's again a lot of overlap. Again, those drugs are also approved for IBS with constipation. I've already mentioned linaclotide at the higher dose for IBS-C. Lubiprostone is approved at a lower dose for IBS with less nausea at 8 micrograms twice a day. And then we have plecanatide, which is approved at the same dose for CIC.

In addition, there's also a new drug called Ibsrela (tenapanor, Ardelyx) which is also in that category of secretagogues. The nomenclature may be a little bit different but the bottom line is they increase secretions. In this case, tenapanor will block the sodium absorption. So it works by a different mechanism. And for prokinetics, prucalopride is not approved for IBS with constipation. But tegaserod is approved, which is a another 5-HT4 agonist. And I think most of you know that although it is approved, the manufacturer recently removed it from the market, mainly for economic reasons, not for new safety reasons. It was only approved in a relatively small subset of patients, with women under the age of 65 without cardiovascular side of effects. So it's really not available to date.

So those are the FDA-approved medication. Now, in addition, we also have the osmotic laxatives and the fiber, all of which could pertain to IBS with constipation and generally in the AGA guidelines, we do recommend starting with the osmotic and a fiber laxative in patients with IBS-C, despite the lack of definitive therapy. Just again, what I said, its safety profile's very good, it's relatively inexpensive and it's widely available. So it's important to know that as well.

With IBS-C, when pain is the predominant symptom then we may have to add a neuromodulator. So a lot of these FDA-approved drugs have been shown to improve bowel function as well as abdominal symptoms. But sometimes pain is really the predominant symptom and it's there even when the bowels are working fine with medications. There we would add a neuromodulator. We don't have great ones that don't cause constipation but we do tend to use the tricyclic antidepressants even though they do have anticholinergic effects, may cause some constipation. But the dose that we use it has relatively low, and I think most of us know that it started tricyclic at 10 milligram going up to 25 or 50. Really you don't tend to get a lot of constipation, particularly at the lower doses. So I still will start at the lower doses.

My go-to medication would be one of the tricyclic antidepressants. Typically, I would use something like desipramine that may have less of the anticholinergic side effects which I'm trying to avoid in someone with constipation. SSRIs are generally not recommended, and that was from the AGA guidelines. And I know some of you may say, "Well, I'm using medications." We didn't include an analysis of duloxetine. It just hasn't been studied. Clinically, I know some people, myself included, may use duloxetine when I have someone with severe pain and particularly if a tricyclic hasn't worked.

Now, some of you may be asking what about probiotics, other antispasmodics, things such as the anticholinergic ones, hyoscyamine or peppermint oil. And again, there there's not a lot of strong evidence for them, with the exception of peppermint oil, which is recommended because there there's a number of studies and several meta-analysis showing improvement in most but not all of the studies showing improvement in patients with IBS. So we will tend to use those particularly for abdominal pain and typically when the pain is intermittent. So we use it on an as-needed or a PRN basis.

So finally, in some patients, particularly those with comorbid psychological conditions, such as anxiety and depression or prior history, psychological therapy may be effective. We now have several FDA-cleared apps that are available including ones for hypnosis and CBT that have been shown to be effective in patients with IBS. And having them widely available may be very helpful if you don't have a GI psychologist like we're fortunate here at Cleveland Clinic to have excellent GI psychologists that we can refer to. But of course, they're not widely available.