Treatment of IBS
 

Susan, traditional treatments for IBS have included some drugs and some nonpharmacological modalities. What are some of these modalities, and how do you initiate the treatment?

Susan Lucak MD: I think it's very important to establish a good relationship with a patient, and to educate patients about irritable bowel syndrome and tell them it's not just a disorder in their heads. It's important also to reassure a patient that this will not lead to something serious like colon cancer. In addition, there are some dietary changes that a patient may need to make. They may have lactose intolerance that may make their symptoms worse and it's important to identify that.

Patients also need to understand that there are certain lifestyle factors. For example, if they are under stress, that may worsen their irritable bowel syndrome. Certain foods they eat may worsen their symptoms. You must identify those factors and then eliminate them, for instance through stress reduction. There are nonpharmacologic treatments, and then there are pharmacologic treatments.

Peter Salgo MD: Larry, it's often tempting to give medications, but if you start from first principles, changes in diet are often the way that physicians approach this problem. So what do you recommend and how effective is dietary change?

Lawrence Schiller MD: I think diet can be important in some individuals. It certainly is a trigger for symptoms. It's important to know the foods that the patient realizes causes his or her problems. In that regard, it may be useful to keep a diet diary for a couple of weeks, have them write down what they're eating and the approximate amounts. Then, in the second column, you can have them enter the symptoms they're having and then try to make some correlations that way.

Peter Salgo MD: So it's not just enough to add stuff, you might want to subtract things from their diet. Is that right?

Lawrence Schiller MD: Absolutely. Many of them have problems with carbohydrate malabsorption. They may have lactose intolerance or have difficulties with digesting wheat starch or other materials. This may cause them to have excess gas and bloating as a result.

Peter Salgo MD: Lin, are there any adverse effects from increasing the fiber intake?

Lin Chang MD: Some of the adverse events from fiber intake would be bloating, even abdominal cramps, loose stools. So often what I do is start them on a lower dose of a fiber, if they're not used to a high-fiber diet and then gradually increase it and see how they tolerate.

Peter Salgo MD: Susan, what are the old standbys, the traditional medications that you would think of in IBS with constipation?

Susan Lucak MD: There are laxatives that can be used in addition to fiber. The laxatives that we have classically used are the osmotic-type laxatives that include milk of magnesia, lactulose. More recently, MiraLax has been introduced on the market for the treatment of constipation.

Peter Salgo MD: But not the stimulant laxatives at all, is that right?

Susan Lucak MD: They can be used on short-term basis. Generally, we have been recommending the osmotic-type laxatives.

Peter Salgo MD: Larry, what are the new approaches that are available now for IBS patients with constipation?

Lawrence Schiller MD: I think the new development in the last year has been the release of tegaserod for treating these patients. This is a drug that's a 5-HT4 receptor agonist. What it does is to stimulate peristalsis and improve gastrointestinal transit. It ends up causing people to have more stools than they would have otherwise, but in addition it reduces pain and bloating to a significant degree.

Peter Salgo MD: This is only been approved (in the U.S.A) for use in women, right?

Lawrence Schiller MD: Absolutely.

Peter Salgo MD: What about men? Where do they stand in this?

Lawrence Schiller MD: It's not clear. The studies that were done enrolled predominantly women, so there weren't enough men to make a statistical comment. The FDA decided to go with the data and limit its use to women for now.

Peter Salgo MD: Does tegaserod improve global IBS symptoms or is it just for constipation, Lin?

Lin Chang MD: It's actually been shown to provide global relief of IBS symptoms in women with IBS with constipation. It also has been shown to help specific symptoms as pain, bloating.

Peter Salgo MD: What are the adverse effects of the drug?

Peter Salgo MD

Susan Lucak MD

Susan Lucak MD: The adverse effects are really minimal. Of the patients who have been on tegaserod, about 9% of them experience diarrhea. Diarrhea usually occurs very early on in the treatment, usually in the first week, and then after a week the diarrhea disappears. It's not an incapacitating diarrhea; typically patients will have approximately four bowel movements per day. Then after a week, this disappears.

The second side effect is non-migraine headache; approximately 15% of patients who have been on tegaserod experienced headache versus approximately 12% of placebo patients. So it's only a few patients who develop headache. Again, it is a non-migraine headache; it tends to respond to treatment with Tylenol and it may not be long-lasting in many patients.

Peter Salgo MD: All right. Let's take a look at the diarrheal component of IBS. Larry, what are the traditional medications that you start patients on for this?

Lawrence Schiller MD: For the symptom of abdominal pain and for bloating, we treat that very much like we do the IBS with constipation. I rely a lot on the tricyclic antidepressant drugs for pain control. And in the case of patients with diarrhea, the anticholinergic effects are a benefit, because they will tend to somewhat reduce their stool frequency .

As far as dealing with the excess stools, the use of antidiarrheals is often very effective.

Peter Salgo MD: Lin, what are the mechanisms of action of these things?

Lin Chang MD: Some of these antidiarrheal agents are actually opiate-type agents. They slow down gut motility and enhance absorption, so the stool is not so loose.

Susan Lucak MD: One of the symptoms that patients with diarrhea have is urgency. Many of the treatments that we have had available to us did not treat the symptom. It's a very important symptom that patients experience, because sometimes they don't mind having five or six bowel movements per day, as long as they can make it to the bathroom on time. That has been a really problematic symptom to treat in patients with diarrhea-predominant irritable bowel syndrome.

Peter Salgo MD: Well, why don't you take me through what new approaches are available for IBS with the diarrheal component, then?

Susan Lucak MD: Alosetron, which is a serotonin type 3 receptor antagonist, is a medication that was approved in the year 2000 for diarrhea-predominant irritable bowel syndrome in women. It was taken off the market nine months later and was been reintroduced on the market late last year. It's a medication that decreases stool frequency. It is probably the best medication to treat urgency. It also improves consistency, in that it makes stools more formed. And it helps with abdominal pain.

Peter Salgo MD: Lin, why was it removed from the market?

Lin Chang MD: It was withdrawn because of serious adverse events. There was an association with severe constipation, but that may be due to several reasons; perhaps giving it to patients that didn't fit the subgroup of IBS with diarrhea. Also, there was some type of relationship to ischemic colitis, occurring in 0.1%, up to 1% of patients taking alosetron.

Peter Salgo MD: Weren't there some patient deaths involved?

Lin Chang MD: It was a complicated history. The patients had several medical conditions on multiple medications. I don't think there's been any causal association of alosetron with those deaths.

Peter Salgo MD: So now alosetron is back. What changes have been made in the prescribing and monitoring procedures for this drug since its return?

Lin Chang MD: It's under restricted use. Physicians have to get a binder that has the information about alosetron. They have to inform the patients that they want to prescribe the drug, and the patients have to read an agreement form and sign it. Then the physicians get a sticker that they have to place on their prescription slip. The pharmacist will only fill the prescription if it has that sticker. And there can be no refills; prescriptions have to be written every month. You start at a lower dose, 1 mg once a day, and then increase it, if needed.

Peter Salgo MD: It got that black box warning, right?

Lin Chang MD: Right, it did.

Peter Salgo MD: Susan, I want to go through some of these therapies and adverse effects with you. Just bullet points.

So, with laxatives, what do you watch out for?

Susan Lucak MD: Excessive use can lead to diarrhea.

Peter Salgo MD: Anticholinergics?

Susan Lucak MD: Constipation.

Peter Salgo MD: Tricyclic antidepressants?

Susan Lucak MD: Constipation, weight gain, tachycardia, urinary retention.

Peter Salgo MD: What do you watch out for with alosetron?

Susan Lucak MD: Constipation and possible ischemic colitis.

Peter Salgo MD: That's a big one. What about tegaserod?

Susan Lucak MD: Diarrhea and headaches.

Peter Salgo MD: Larry, I want to talk now about the pain component of IBS. How do you approach that?

Lawrence Schiller MD: It's a very difficult issue. Pain in IBS can be anything from a mild discomfort to something that's earth-shatteringly severe and has a major impact on these individuals. I think you need to tailor your anti-pain therapy to the degree of discomfort that the person has. Certainly, if they have residual pain after some of the treatments that have been talked about, I think that needs to be addressed.

Personally, I use all the different tools that we have available: the pain-modifying drugs, the old tricyclic antidepressant type, as well as some of the real analgesic medicines including the opiates. That's a very controversial point, though. I have partners who are unwilling to give opiates to anyone who has irritable bowel syndrome as a diagnosis.

Peter Salgo MD: Why is that?

Lawrence Schiller MD: I think they're afraid of misuse of the medicine, and I can share their concerns, but when you're confronted with a patient with a devastating problem, sometimes you have to take that chance.

Peter Salgo MD: Are antispasmodics okay? What do you think, Lin?

Lin Chang MD: I think they're used very frequently by primary care physicians and gastroenterologists. There are some studies that have shown that certain antispasmodics are more effective over placebo, although those aren't the antispasmodics that are available in the United States. I think sometimes it can help take the edge off the pain and may be useful for abdominal pain, but I think there are probably better agents for the treatment of pain.

Susan Lucak MD: My personal view is that antispasmodic medications are not very effective. They are effective in a mild form of irritable bowel syndrome, but not in the more severe forms.

I would like to make one point about the use of opiates in irritable bowel syndrome. My experience with opiates is that the visceral pain that patients with irritable bowel syndrome have does not tend to respond well to opiates. I find that I wind up with patients who come to me for a second or third opinion, with drug dependence and irritable bowel syndrome and needing to put on increasing doses of opiates to deal with the pain. My personal experience has been that these individuals often have significant psychiatric comorbidity and it is this that needs to be treated more aggressively. I have been able to then detoxify their opiate dependence or their opiate use and treat the depression or anxiety in consultation with a psychiatrist. And I have had more success with bringing their symptoms under better control in this way.

Lin Chang MD: I think there's an important distinction, though. If you start talking about patients with severe abdominal pain that's chronic, that's not really associated with defecation or stool - changes in stool frequency or stool consistency - then you're really talking about chronic abdominal functional pain. Tat's really separate from irritable bowel syndrome. With those patients you would want to do psychiatric or psychological therapy and also combine it with centrally-acting agents.

Peter Salgo MD: These two new serotonin agents, how effective are they in controlling the pain of this syndrome?

Susan Lucak MD: They are effective in most patients, but in those where there may be some residual pain, then other medications that will decrease sensitivity of the gut may need to be used in addition.

Peter Salgo MD: Lin, what promising new agents are on the horizon?

Lin Chang MD: I think that, with research evolving as it has, we'll find more targets that we can develop therapies against or for to help in the treatment of abdominal pain in IBS.

Peter Salgo MD: What about the kappa opioids?

Lin Chang MD: That's a drug class that shows some promise. There have been some negative studies and one in particular. But there are other drugs such as cholecystokinin antagonists, MK1 and MK3 antagonists, even clonidine, which has been used for hypertension, for IBS as well.

Peter Salgo MD: What are some precautions that need to be considered when you're prescribing medications for IBS, specific to IBS and IBS patients?

Susan Lucak MD: As we now have new agents that have become available to us, I think what is important is to recognize that they are new and that when they are prescribed, they need to be prescribed appropriately in patients. Patients need to be assessed properly and then, once the medication is prescribed, the patient must be followed carefully. The patient should not just be sent out on the medication but also be brought back and monitored.

Once we have more information, once we have more data on a variety of these new medications, then we can perhaps relax. But I think - particularly early on - we need to follow patients closely.

Peter Salgo MD: I want to thank all of you for being here; I want to thank you for watching. I'm Dr Peter Salgo.

Susan Lucak MD