Treatment using Medications or other forms of medical intervention
Currently there are no FDA-approved medications that are labeled to treat microscopic colitis, nor have there ever been. Ever since the first known form of microscopic colitis ( collagenous colitis) was described, the disease has mostly been considered by the medical community to be rare, so it’s not surprising that to date at least, no pharmaceutical company has been willing to invest the huge sums of money required to obtain FDA approval for one or more drugs specifically labeled to treat it. Consequently, if doctors are to prescribe a medication to treat MC, they are forced to prescribe an existing FDA-approved drug, for off-label use.
Typically, drugs labeled for the treatment of Crohn's disease or ulcerative colitis are prescribed to treat microscopic colitis. Because the FDA does not have the legal authority to regulate the practice of medicine, a physician may prescribe a drug for off-label use without FDA approval. And although it’s legal for a physician to prescribe a drug for an off-label use, it is not legal for a pharmaceutical company to promote the use of a drug for an off-label use.
In recent years, physicians are beginning to realize that microscopic colitis is not rare after all (it was simply under-diagnosed for many years), so now there is at least a possibility that one or more pharmaceutical companies may decide to develop a drug specifically labeled to treat microscopic colitis at some point in the future. At the very least, maybe one of them will petition the FDA to allow them to add microscopic colitis to the label of an existing FDA-approved medication.
A surprising number of cases of microscopic colitis are drug-induced. When this occurs, remission can sometimes be achieved by simply discontinuing the use of the drug that caused the symptoms. And as long as the patient avoids that class of medications in the future, remission from the disease may be maintained indefinitely. But based on empirical evidence, it appears that patients with drug-induced MC may be the only subset of patients who are consistently able to enjoy long-term remission, without any continued treatment intervention.
In many cases however, especially when symptoms have been active for many years, simply discontinuing the use of the drug may not be sufficient to establish and maintain remission. In those cases, too much damage may have accrued to the intestines, and additional treatment intervention may be necessary.
As part of their treatment recommendations, most gastroenterologists advise MC patients to avoid certain drugs that are known to be commonly associated with the onset of microscopic colitis. One of the first classes of medications recognized to cause microscopic colitis is known as nonsteroidal anti-inflammatory drugs (NSAIDs). Since then, additional drugs have been added to the list, including antibiotics, proton pump inhibitors (PPIs), selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, angiotensin-converting enzyme (ACE) inhibitors, beta blockers, statins, and bisphosphonates, There are surely others that have not yet been identified.
The Pepto-Bismol (bismuth subsalicylate) treatment
The first treatment regimen specifically developed for treating microscopic colitis was demonstrated approximately a couple of decades ago in a controlled trial, by a medical researcher who happened to have microscopic colitis himself, Dr. Kenneth Fine. In the clinical trial he and his associate proved that Pepto-Bismol (which contains bismuth subsalicylate as the active ingredient) could bring remission of MC symptoms if it were taken in substantial doses (eight tablets, or equivalent doses) each day for a period of eight weeks. While this trial involved only a relatively small number of subjects, the data indicated that diarrhea was resolved for 75 % of the subjects who completed the trial. The average response time (to reach remission) was two weeks, and there were no significant side effects noted in the research report.
The mechanism by which bismuth subsalicylate suppresses inflammation is not known, but it is known that bismuth subsalicylate has slight antibiotic properties. However, Dr. Fine no longer recommends this treatment, primarily because with such a high dosage rate there is a slight risk of a toxic buildup of bismuth in the body if the treatment were to be continued past the recommended interval. In addition, it has since been noted that a few patients may react adversely to dyes or other ingredients in Pepto-Bismol . His subsequent research suggests that treatment with bismuth subsalicylate is usually unnecessary anyway, since remission can typically be attained by diet changes alone. You can click on the "Using Diet Changes" tab for information on using diet changes to control microscopic colitis.
Treatments that slow down gut motility
Certain Medications known to slow down gut motility can be used treat diarrhea. These medications work by reducing the peristaltic pumping action of the intestines. Lotronex, (alosetron), is one of the drugs in this category, although it is mostly used to treat IBS. Occasionally it is prescribed to treat MC. For most patients, it tends to be a very powerful anti-motility agent — so effective that it has a rather rocky past, due to inappropriate use when it was first approved for sale. In the year 2000 it was pulled from the market only nine months after its fast-track approval by the FDA, because of a number of fatalities associated with its use.
The problem was that many doctors prescribed it not only for use by patients with diarrhea-predominant IBS, but they also prescribed it for use by patients with constipation-predominant IBS. A number of those patients in the latter category developed ischemic colitis, obstruction, perforation, toxic megacolon, and/or other severe, and in some cases life-threatening issues that sometimes required surgical intervention.
The drug was reintroduced in 2002 with new label requirements that stipulated that before a doctor could prescribe the drug, he or she must register with the manufacturer and receive special training designed to reduce the chances of the drug being prescribed to a patient who might be at risk of a life-threatening reaction. The new regulations also stipulate that Lotronex can only be prescribed for use by women with diarrhea-predominant IBS. These days, this drug is not commonly used to treat MC.
Antidiarrheals such as Imodium (Loperamide) and Lomotil (Diphenoxylate and atropine) also help to control diarrhea by slowing motility. Lomotil requires a prescription, while Imodium is available without any prescription requirement. Despite the fact that Imodium is available over-the-counter, many patients find it to be just as effective as Lomotil, and some patients have even found that Imodium works better for them than Lomotil.
Antispasmodics
Drugs in this category work by suppressing the motility of the stomach and intestines, and by reducing the secretion of stomach acid and other fluids. This group of drugs is based on belladonna alkaloids and phenobarbital, including atropine, hyoscyamine, and scopolamine. Levsin (hyoscyamine) appears to be the drug in this group most likely to be prescribed for treating microscopic colitis, but it is not often prescribed to treat the disease. In general, this class of drugs is most often used to treat the symptoms of IBS or ulcers, and medications in this group are seldom prescribed to treat microscopic colitis.
Bile acid sequestrants
Medications in this category are known as hypolipidemic agents because they are primarily used to restrict the reabsorption of bile acids. Originally they were developed for the purpose of lowering cholesterol levels, but they are often prescribed to reduce diarrhea, especially in the case of patients who have recently had gallbladder surgery. Bile acid sequestrants tie up bile salts so that they are no longer in a form where they might trigger diarrhea. These medications include cholestyramine, colestipol, and colesevelam, and they tend to cause constipation. Because of that characteristic, some doctors prescribe them to be used by patients who have microscopic colitis.
A research study of collagenous colitis patients completed over 15 years ago, concluded that approximately 44 % of the subjects in the study had bile acid malabsorption (BAM) which was the cause of their intractable diarrhea.1 Treatment with a bile acid sequestrant resulted in symptom improvement in 78 % of the patients.
While this group of medications may be effective at reducing, or even stopping diarrhea in some cases, in other cases they sometimes cause an increase in bloating and pain. Therefore patients using this treatment should pay attention to what their body is telling them, because the treatment is not helpful for everyone who has MC. And of course treatments in this category do not address the underlying cause of the inflammation that leads to the development and perpetuation of MC and bile acid malabsorption. They only treat the symptom of bile acid malabsorption.
Antidepressants
Many antidepressants have a side effect of constipation, and this is the reason why various antidepressants are sometimes prescribed to treat MC. The most popular choices for this use seem to be the selective serotonin reuptake inhibitors (SSRIs) and the serotonin-norepinephrine reuptake inhibitors (SNRIs). Because depression seems to be commonly associated with this disease anyway, in some cases anti-depressants may provide additional benefits (provided that they are successful in providing some degree of depression relief).
It's also possible that the anti-anxiety attributes of some of these medications may also provide some benefits for reducing muscular contractions in the gut. Obviously this class of drugs does nothing to suppress the inflammation that leads to the development of MC in the first place, but for some people, stopping the diarrhea provides sufficient symptomatic relief that they consider the treatment to be a success. Whether ignoring the inflammation is a prudent choice, is a topic that is open to debate.
Not surprisingly, for many patients these drugs do not resolve the diarrhea. And for other patients, they may even cause the existing symptoms to become worse. The relatively high risk of side effects, and the risk that the body may develop a dependency on these drugs with long-term use, requiring the dosage to be tapered when their use is to be discontinued, further complicates prescribing these drugs to treat MC.
While an antidepressant might help to relieve diarrhea in some cases where diarrhea is the predominant gastrointestinal symptom of MC, this class of drugs would obviously be contraindicated in cases where constipation is the predominant GI symptom, or where alternating diarrhea and constipation is the rule. And of course SSRIs and SNRIs would also be contraindicated in any case where the patient is sensitive to the drug, as indicated by an adverse reaction of any type. As mentioned at the beginning of this discussion, this class of drugs has been associated with causing MC in a significant number of cases, so they should be used with caution and discontinued if the patient's symptoms become worse.
That said, in certain cases of MC where intestinal motility is too slow, some patients have found that a very low dose of amitriptyline (10 mg per day) seems to help regulate gut motility and may help to establish and maintain remission during the recovery process. This illustrates how different the response to certain drugs can be in different cases.
Painkillers
Because NSAIDs are contraindicated for MC patients, the only non-narcotic painkiller known to be safe for use by someone with MC appears to be Tylenol (acetaminophen). Unlike most narcotic painkillers however, Ultram (tramadol) typically does not cause patients to build up a tolerance after extended use, so it has a very low risk of addiction compared with most of the other narcotic painkillers, such as oxycodone or hydrocodone. That said, please keep in mind that a few patients have discovered that they are exceptions to this rule, and tramadol seems to cause addictive issues for them.
Narcotic painkillers are sometimes prescribed to treat MC, not only for their analgesic effect, but because they slow down motility and tend to cause constipation. Therefore please keep in mind that in addition to the risk of addiction, the use of narcotic type painkillers to treat MC carries a risk of possibly causing a life-threatening fecal impaction problem. And as is the case with many medications, using narcotic-based painkillers to treat MC amounts to only treating the symptoms, while ignoring the inflammation that causes the disease.
5-aminosalicylic acid (5-ASA)
As mentioned earlier in this discussion, the drugs most often prescribed for treating microscopic colitis tend to be those that have been shown to be effective for treating the other inflammatory bowel diseases. In the early days, sulfasalazine (Azulfidine), was often prescribed to treat MC.
Sulfasalazine is a prodrug. That is to say, sulfasalazine does not become active in the digestive system until it is broken down by bacteria in the colon into 5-aminosalicylic acid (5-ASA) and sulfapyridine. Sulfapyradine is known to have a therapeutic effect for rheumatoid arthritis. However, no beneficial effect from sulfapyradine has been described for treating inflammatory bowel disease. Since many people tend to react adversely to sulfa drugs, these days sulfasalazine has mostly been replaced with mesalamine, sometimes referred to as mesalazine, for the treatment of IBDs.
Mesalamine contains the active moiety of sulfasalazine, known as 5-aminosalicyclic acid. There are a number of drugs in this group that use the same active ingredient, and they are sometimes referred to as 5-ASA drugs. In the United States, this group of drugs includes a number of popular brands, including Asacol, Asacol HD, Lialda, Apriso, Colazal, Pentasa, and Rowasa. In the United Kingdom, the brand names commonly available include Asacol, Canasa, Ipocal, Salofalk, and Mezavant XL.
Other brands are available in other countries, but they are all based on mesalamine as the active ingredient. They all use some form of enteric coating to prevent the medication from becoming activated before it reaches the targeted area of the digestive tract, which is usually somewhere in the vicinity of the lower third of the small intestine (the ileum), and the colon. Unfortunately, mesalamine is chemically related to aspirin, so people who are allergic to aspirin, or other salicylates, should not use this medication.
And there is also a risk that this chemical similarity may extend to other attributes of NSAIDs. Even though in vitro studies have shown that mesalamine apparently inhibits the enzymes believed to be responsible for the production of both leukotrienes and prostaglandins (both known to be inflammatory mediators), case studies show that in certain individuals, and in conjunction with inflammatory bowel disease, mesalamine may promote the production of leukotrienes, similar to NSAIDs, resulting in diarrhea or intestinal inflammation, or both. That implies that the 5-ASA drugs may benefit some patients with MC, while causing the inflammation to become worse in other cases.
Experience shows that in general, the medications in this group are relatively effective at suppressing the inflammation that is associated with MC, but they tend to be somewhat slow to bring remission. Typically, they require several weeks or longer, before control is established. They don’t always successfully control the symptoms and some patients cannot tolerate them.
Corticosteroids
Another type of medication commonly prescribed to treat microscopic colitis is the corticosteroids. Corticosteroids are well known for suppressing inflammation, and this class of drugs is generally more effective for most patients than the 5-ASA medications in bringing remission of symptoms. Unfortunately though, some of the corticosteroids have earned a reputation for causing Draconian side effects, if taken on a long-term basis.
One of the corticosteroids that was traditionally prescribed in years past, is prednisone, and some gastroenterologists still prescribe it to treat MC. However, due to its rather significant risk of somewhat serious side effects, it cannot be used for long-term treatment without incurring an unacceptably high risk of adverse health effects. Its primary advantages are low cost and potent efficacy. Part of its effectiveness is due to its immunosuppressive effect. Of course this immunosuppressive effect also has the not insignificant disadvantage of lowering the body’s resistance to disease and infections. And because of its powerful effect on the body’s adrenals, withdrawal from the drug must be carefully managed by means of slowly decreasing the dosage, during the withdrawal period. It has also been documented by research that another disadvantage of using prednisone and other corticosteroids is that they interfere with wound healing, resulting in longer times required for healing, and a possible increase in the risk of infection.
A more modern corticosteroid, budesonide, can often be used just as effectively as prednisone, and it carries a much lower risk of causing adverse health effects. Budesonide is the active ingredient in Entocort EC. Entocort EC capsules offer the advantage of a special enteric coating that delays the activation of the budesonide until it reaches the lower third of the small intestine and the colon, so that only a minimal amount of the active ingredient is absorbed into the bloodstream. Clinical trials show that when budesonide is administered in this way, only nine to 21 % of it is absorbed into the bloodstream. The relatively low rate of absorption into the bloodstream tends to significantly diminish the risk of systemic side effects. That means that the lion’s share of the medication is available to treat the inflamed areas of the ileum and the colon, and that makes Entocort EC an effective, yet much safer medication to use, compared with prednisone.
Arguably the biggest advantage that Entocort EC has over the other corticosteroids for treating MC is that it has been shown to be safe for long-term use. Clinical trials lasting for 52 weeks have demonstrated that the risk of side effects for long-term use of Entocort EC at six mg per day is similar to the risk associated with short-term use (eight weeks) of Entocort EC at nine mg per day, thus establishing its safety for long-term use at six mg per day.
An even newer medication based on budesonide is available. It's called Uceris, and it's manufacturer claims that due to the fact that it does not become activated until it is well down in the colon, there is no risk of any systemic effect at all, and therefore no tapered withdrawal regimen is required with this particular corticosteroid. Uceris is labeled for ulcerative colitis, and UC typically begins at the rectal end of the digestive tract and spreads upward, thus the reason for the manufacturer designing the drug to become active so far down in the digestive tract. While this is ideal for treating UC, Uceris might not be as effective for treating MC in some cases, due to the fact that MC typically affects random areas scattered over the entire colon, and more often than not the terminal ileum is also inflamed. However, reports from MC patients who have used Uceris have been generally favorable.
Immune system suppressants
A few GI specialists have been known to prescribe certain powerful immune system suppressants such as Imuran (azathioprine) or methotrexate to treat MC. These immune system suppressants were originally developed to help reduce rejection rates after organ transplants and for chemotherapy connected with cancer treatments, but they are often prescribed to treat Crohn’s disease.
Azathioprine is another prodrug. During the digestive process, it is metabolized into the active form, 6-mercaptopurine, which impedes DNA synthesis. This in turn retards the propagation of new cells, especially lymphocytes. Normally, lymphocytes tend to grow rapidly. T cells and B cells are particularly affected by this growth restriction. It is generally thought that excessive numbers of T-cells are primarily responsible for the inflammation associated with MC (and other autoimmune issues). Because of the ability of Azathioprine to suppress the propagation of T-cells, it is effective for treating certain autoimmune diseases and it's commonly used to treat Crohn’s disease, thus establishing its potential effectiveness for treating MC.
Methotrexate is used in the treatment of cancer, autoimmune diseases such as rheumatoid arthritis, psoriasis, and psoriatic arthritis. It has even been used to induce medical abortions. It works by inhibiting the metabolism of folic acid. It was originally developed as a chemotherapy treatment and it is known to be effective against a number of different types of cancers. At present however, unlike azathioprine, it appears that methotrexate is rarely prescribed to treat microscopic colitis.
In general, since immune system suppressants carry an elevated risk of developing an infection or cancer, this class of drugs should only be considered if all other less risky treatments have been tried and failed to provide relief of symptoms.
Anti-TNF medications
The anti-tumor necrosis factor medications (anti-TNF) such as Embrel (Etanercept), Remicade (Infliximab), and Humira (Adalimumab) are increasingly being prescribed for treating various inflammatory issues, including Crohn’s disease. Because of that, some doctors view them as a possible option for treating microscopic colitis. This class of drugs is a relatively recent development however, and case studies show that while most patients with inflammatory issues may show benefits, a very small percentage of patients experience severe, and even life-threatening adverse events.
The anti-TNF drugs, for example, have recently been linked with an increased risk of a possibly fatal infection with legionella and listeria bacteria, in addition to the long list of pathogens that were previously listed. While they are deemed to be generally safe for most patients, careful consideration should be given before using one of these drugs, because they work by suppressing the immune system, and that can lead to a significantly increased risk of infections and other adverse events.
Surgical Intervention
As a last resort treatment, some gastroenterologists may even recommend an ileostomy in certain severe cases of MC where the patient does not respond to conventional medical treatment methods. An ileostomy diverts the fecal stream into an external pouch, totally bypassing the colon, and thus preempting any opportunity for colonic inflammation, by isolating the colon from the fecal stream. Published case studies show that this surgical procedure will usually bring remission from symptoms. But using such a radical treatment method seems not unlike burning down the barn in order to get rid of the rats, since the colon will no longer provide any functional benefits to the body after the procedure. And if the small intestine is involved in the reactions (and this appears to be the case for many patients), then an ileostomy could not be expected to resolve the reactions that originate in the small intestine.
But the claims that this procedure will always bring remission, are simply not true. There are cases where an ileostomy will not resolve MC symptoms. If an elemental diet, especially if the food is delivered by means of an enteral feeding tube, will not resolve the symptoms, then it would be pointless to pursue a solution by means of an ileostomy because the procedure will almost surely not resolve the diarrhea, nor any of the other symptoms. Therefore, very careful consideration should be given to the details of each individual case before deciding to try this procedure, because it is not a guaranteed cure for microscopic colitis.
Typically, drugs labeled for the treatment of Crohn's disease or ulcerative colitis are prescribed to treat microscopic colitis. Because the FDA does not have the legal authority to regulate the practice of medicine, a physician may prescribe a drug for off-label use without FDA approval. And although it’s legal for a physician to prescribe a drug for an off-label use, it is not legal for a pharmaceutical company to promote the use of a drug for an off-label use.
In recent years, physicians are beginning to realize that microscopic colitis is not rare after all (it was simply under-diagnosed for many years), so now there is at least a possibility that one or more pharmaceutical companies may decide to develop a drug specifically labeled to treat microscopic colitis at some point in the future. At the very least, maybe one of them will petition the FDA to allow them to add microscopic colitis to the label of an existing FDA-approved medication.
A surprising number of cases of microscopic colitis are drug-induced. When this occurs, remission can sometimes be achieved by simply discontinuing the use of the drug that caused the symptoms. And as long as the patient avoids that class of medications in the future, remission from the disease may be maintained indefinitely. But based on empirical evidence, it appears that patients with drug-induced MC may be the only subset of patients who are consistently able to enjoy long-term remission, without any continued treatment intervention.
In many cases however, especially when symptoms have been active for many years, simply discontinuing the use of the drug may not be sufficient to establish and maintain remission. In those cases, too much damage may have accrued to the intestines, and additional treatment intervention may be necessary.
As part of their treatment recommendations, most gastroenterologists advise MC patients to avoid certain drugs that are known to be commonly associated with the onset of microscopic colitis. One of the first classes of medications recognized to cause microscopic colitis is known as nonsteroidal anti-inflammatory drugs (NSAIDs). Since then, additional drugs have been added to the list, including antibiotics, proton pump inhibitors (PPIs), selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, angiotensin-converting enzyme (ACE) inhibitors, beta blockers, statins, and bisphosphonates, There are surely others that have not yet been identified.
The Pepto-Bismol (bismuth subsalicylate) treatment
The first treatment regimen specifically developed for treating microscopic colitis was demonstrated approximately a couple of decades ago in a controlled trial, by a medical researcher who happened to have microscopic colitis himself, Dr. Kenneth Fine. In the clinical trial he and his associate proved that Pepto-Bismol (which contains bismuth subsalicylate as the active ingredient) could bring remission of MC symptoms if it were taken in substantial doses (eight tablets, or equivalent doses) each day for a period of eight weeks. While this trial involved only a relatively small number of subjects, the data indicated that diarrhea was resolved for 75 % of the subjects who completed the trial. The average response time (to reach remission) was two weeks, and there were no significant side effects noted in the research report.
The mechanism by which bismuth subsalicylate suppresses inflammation is not known, but it is known that bismuth subsalicylate has slight antibiotic properties. However, Dr. Fine no longer recommends this treatment, primarily because with such a high dosage rate there is a slight risk of a toxic buildup of bismuth in the body if the treatment were to be continued past the recommended interval. In addition, it has since been noted that a few patients may react adversely to dyes or other ingredients in Pepto-Bismol . His subsequent research suggests that treatment with bismuth subsalicylate is usually unnecessary anyway, since remission can typically be attained by diet changes alone. You can click on the "Using Diet Changes" tab for information on using diet changes to control microscopic colitis.
Treatments that slow down gut motility
Certain Medications known to slow down gut motility can be used treat diarrhea. These medications work by reducing the peristaltic pumping action of the intestines. Lotronex, (alosetron), is one of the drugs in this category, although it is mostly used to treat IBS. Occasionally it is prescribed to treat MC. For most patients, it tends to be a very powerful anti-motility agent — so effective that it has a rather rocky past, due to inappropriate use when it was first approved for sale. In the year 2000 it was pulled from the market only nine months after its fast-track approval by the FDA, because of a number of fatalities associated with its use.
The problem was that many doctors prescribed it not only for use by patients with diarrhea-predominant IBS, but they also prescribed it for use by patients with constipation-predominant IBS. A number of those patients in the latter category developed ischemic colitis, obstruction, perforation, toxic megacolon, and/or other severe, and in some cases life-threatening issues that sometimes required surgical intervention.
The drug was reintroduced in 2002 with new label requirements that stipulated that before a doctor could prescribe the drug, he or she must register with the manufacturer and receive special training designed to reduce the chances of the drug being prescribed to a patient who might be at risk of a life-threatening reaction. The new regulations also stipulate that Lotronex can only be prescribed for use by women with diarrhea-predominant IBS. These days, this drug is not commonly used to treat MC.
Antidiarrheals such as Imodium (Loperamide) and Lomotil (Diphenoxylate and atropine) also help to control diarrhea by slowing motility. Lomotil requires a prescription, while Imodium is available without any prescription requirement. Despite the fact that Imodium is available over-the-counter, many patients find it to be just as effective as Lomotil, and some patients have even found that Imodium works better for them than Lomotil.
Antispasmodics
Drugs in this category work by suppressing the motility of the stomach and intestines, and by reducing the secretion of stomach acid and other fluids. This group of drugs is based on belladonna alkaloids and phenobarbital, including atropine, hyoscyamine, and scopolamine. Levsin (hyoscyamine) appears to be the drug in this group most likely to be prescribed for treating microscopic colitis, but it is not often prescribed to treat the disease. In general, this class of drugs is most often used to treat the symptoms of IBS or ulcers, and medications in this group are seldom prescribed to treat microscopic colitis.
Bile acid sequestrants
Medications in this category are known as hypolipidemic agents because they are primarily used to restrict the reabsorption of bile acids. Originally they were developed for the purpose of lowering cholesterol levels, but they are often prescribed to reduce diarrhea, especially in the case of patients who have recently had gallbladder surgery. Bile acid sequestrants tie up bile salts so that they are no longer in a form where they might trigger diarrhea. These medications include cholestyramine, colestipol, and colesevelam, and they tend to cause constipation. Because of that characteristic, some doctors prescribe them to be used by patients who have microscopic colitis.
A research study of collagenous colitis patients completed over 15 years ago, concluded that approximately 44 % of the subjects in the study had bile acid malabsorption (BAM) which was the cause of their intractable diarrhea.1 Treatment with a bile acid sequestrant resulted in symptom improvement in 78 % of the patients.
While this group of medications may be effective at reducing, or even stopping diarrhea in some cases, in other cases they sometimes cause an increase in bloating and pain. Therefore patients using this treatment should pay attention to what their body is telling them, because the treatment is not helpful for everyone who has MC. And of course treatments in this category do not address the underlying cause of the inflammation that leads to the development and perpetuation of MC and bile acid malabsorption. They only treat the symptom of bile acid malabsorption.
Antidepressants
Many antidepressants have a side effect of constipation, and this is the reason why various antidepressants are sometimes prescribed to treat MC. The most popular choices for this use seem to be the selective serotonin reuptake inhibitors (SSRIs) and the serotonin-norepinephrine reuptake inhibitors (SNRIs). Because depression seems to be commonly associated with this disease anyway, in some cases anti-depressants may provide additional benefits (provided that they are successful in providing some degree of depression relief).
It's also possible that the anti-anxiety attributes of some of these medications may also provide some benefits for reducing muscular contractions in the gut. Obviously this class of drugs does nothing to suppress the inflammation that leads to the development of MC in the first place, but for some people, stopping the diarrhea provides sufficient symptomatic relief that they consider the treatment to be a success. Whether ignoring the inflammation is a prudent choice, is a topic that is open to debate.
Not surprisingly, for many patients these drugs do not resolve the diarrhea. And for other patients, they may even cause the existing symptoms to become worse. The relatively high risk of side effects, and the risk that the body may develop a dependency on these drugs with long-term use, requiring the dosage to be tapered when their use is to be discontinued, further complicates prescribing these drugs to treat MC.
While an antidepressant might help to relieve diarrhea in some cases where diarrhea is the predominant gastrointestinal symptom of MC, this class of drugs would obviously be contraindicated in cases where constipation is the predominant GI symptom, or where alternating diarrhea and constipation is the rule. And of course SSRIs and SNRIs would also be contraindicated in any case where the patient is sensitive to the drug, as indicated by an adverse reaction of any type. As mentioned at the beginning of this discussion, this class of drugs has been associated with causing MC in a significant number of cases, so they should be used with caution and discontinued if the patient's symptoms become worse.
That said, in certain cases of MC where intestinal motility is too slow, some patients have found that a very low dose of amitriptyline (10 mg per day) seems to help regulate gut motility and may help to establish and maintain remission during the recovery process. This illustrates how different the response to certain drugs can be in different cases.
Painkillers
Because NSAIDs are contraindicated for MC patients, the only non-narcotic painkiller known to be safe for use by someone with MC appears to be Tylenol (acetaminophen). Unlike most narcotic painkillers however, Ultram (tramadol) typically does not cause patients to build up a tolerance after extended use, so it has a very low risk of addiction compared with most of the other narcotic painkillers, such as oxycodone or hydrocodone. That said, please keep in mind that a few patients have discovered that they are exceptions to this rule, and tramadol seems to cause addictive issues for them.
Narcotic painkillers are sometimes prescribed to treat MC, not only for their analgesic effect, but because they slow down motility and tend to cause constipation. Therefore please keep in mind that in addition to the risk of addiction, the use of narcotic type painkillers to treat MC carries a risk of possibly causing a life-threatening fecal impaction problem. And as is the case with many medications, using narcotic-based painkillers to treat MC amounts to only treating the symptoms, while ignoring the inflammation that causes the disease.
5-aminosalicylic acid (5-ASA)
As mentioned earlier in this discussion, the drugs most often prescribed for treating microscopic colitis tend to be those that have been shown to be effective for treating the other inflammatory bowel diseases. In the early days, sulfasalazine (Azulfidine), was often prescribed to treat MC.
Sulfasalazine is a prodrug. That is to say, sulfasalazine does not become active in the digestive system until it is broken down by bacteria in the colon into 5-aminosalicylic acid (5-ASA) and sulfapyridine. Sulfapyradine is known to have a therapeutic effect for rheumatoid arthritis. However, no beneficial effect from sulfapyradine has been described for treating inflammatory bowel disease. Since many people tend to react adversely to sulfa drugs, these days sulfasalazine has mostly been replaced with mesalamine, sometimes referred to as mesalazine, for the treatment of IBDs.
Mesalamine contains the active moiety of sulfasalazine, known as 5-aminosalicyclic acid. There are a number of drugs in this group that use the same active ingredient, and they are sometimes referred to as 5-ASA drugs. In the United States, this group of drugs includes a number of popular brands, including Asacol, Asacol HD, Lialda, Apriso, Colazal, Pentasa, and Rowasa. In the United Kingdom, the brand names commonly available include Asacol, Canasa, Ipocal, Salofalk, and Mezavant XL.
Other brands are available in other countries, but they are all based on mesalamine as the active ingredient. They all use some form of enteric coating to prevent the medication from becoming activated before it reaches the targeted area of the digestive tract, which is usually somewhere in the vicinity of the lower third of the small intestine (the ileum), and the colon. Unfortunately, mesalamine is chemically related to aspirin, so people who are allergic to aspirin, or other salicylates, should not use this medication.
And there is also a risk that this chemical similarity may extend to other attributes of NSAIDs. Even though in vitro studies have shown that mesalamine apparently inhibits the enzymes believed to be responsible for the production of both leukotrienes and prostaglandins (both known to be inflammatory mediators), case studies show that in certain individuals, and in conjunction with inflammatory bowel disease, mesalamine may promote the production of leukotrienes, similar to NSAIDs, resulting in diarrhea or intestinal inflammation, or both. That implies that the 5-ASA drugs may benefit some patients with MC, while causing the inflammation to become worse in other cases.
Experience shows that in general, the medications in this group are relatively effective at suppressing the inflammation that is associated with MC, but they tend to be somewhat slow to bring remission. Typically, they require several weeks or longer, before control is established. They don’t always successfully control the symptoms and some patients cannot tolerate them.
Corticosteroids
Another type of medication commonly prescribed to treat microscopic colitis is the corticosteroids. Corticosteroids are well known for suppressing inflammation, and this class of drugs is generally more effective for most patients than the 5-ASA medications in bringing remission of symptoms. Unfortunately though, some of the corticosteroids have earned a reputation for causing Draconian side effects, if taken on a long-term basis.
One of the corticosteroids that was traditionally prescribed in years past, is prednisone, and some gastroenterologists still prescribe it to treat MC. However, due to its rather significant risk of somewhat serious side effects, it cannot be used for long-term treatment without incurring an unacceptably high risk of adverse health effects. Its primary advantages are low cost and potent efficacy. Part of its effectiveness is due to its immunosuppressive effect. Of course this immunosuppressive effect also has the not insignificant disadvantage of lowering the body’s resistance to disease and infections. And because of its powerful effect on the body’s adrenals, withdrawal from the drug must be carefully managed by means of slowly decreasing the dosage, during the withdrawal period. It has also been documented by research that another disadvantage of using prednisone and other corticosteroids is that they interfere with wound healing, resulting in longer times required for healing, and a possible increase in the risk of infection.
A more modern corticosteroid, budesonide, can often be used just as effectively as prednisone, and it carries a much lower risk of causing adverse health effects. Budesonide is the active ingredient in Entocort EC. Entocort EC capsules offer the advantage of a special enteric coating that delays the activation of the budesonide until it reaches the lower third of the small intestine and the colon, so that only a minimal amount of the active ingredient is absorbed into the bloodstream. Clinical trials show that when budesonide is administered in this way, only nine to 21 % of it is absorbed into the bloodstream. The relatively low rate of absorption into the bloodstream tends to significantly diminish the risk of systemic side effects. That means that the lion’s share of the medication is available to treat the inflamed areas of the ileum and the colon, and that makes Entocort EC an effective, yet much safer medication to use, compared with prednisone.
Arguably the biggest advantage that Entocort EC has over the other corticosteroids for treating MC is that it has been shown to be safe for long-term use. Clinical trials lasting for 52 weeks have demonstrated that the risk of side effects for long-term use of Entocort EC at six mg per day is similar to the risk associated with short-term use (eight weeks) of Entocort EC at nine mg per day, thus establishing its safety for long-term use at six mg per day.
An even newer medication based on budesonide is available. It's called Uceris, and it's manufacturer claims that due to the fact that it does not become activated until it is well down in the colon, there is no risk of any systemic effect at all, and therefore no tapered withdrawal regimen is required with this particular corticosteroid. Uceris is labeled for ulcerative colitis, and UC typically begins at the rectal end of the digestive tract and spreads upward, thus the reason for the manufacturer designing the drug to become active so far down in the digestive tract. While this is ideal for treating UC, Uceris might not be as effective for treating MC in some cases, due to the fact that MC typically affects random areas scattered over the entire colon, and more often than not the terminal ileum is also inflamed. However, reports from MC patients who have used Uceris have been generally favorable.
Immune system suppressants
A few GI specialists have been known to prescribe certain powerful immune system suppressants such as Imuran (azathioprine) or methotrexate to treat MC. These immune system suppressants were originally developed to help reduce rejection rates after organ transplants and for chemotherapy connected with cancer treatments, but they are often prescribed to treat Crohn’s disease.
Azathioprine is another prodrug. During the digestive process, it is metabolized into the active form, 6-mercaptopurine, which impedes DNA synthesis. This in turn retards the propagation of new cells, especially lymphocytes. Normally, lymphocytes tend to grow rapidly. T cells and B cells are particularly affected by this growth restriction. It is generally thought that excessive numbers of T-cells are primarily responsible for the inflammation associated with MC (and other autoimmune issues). Because of the ability of Azathioprine to suppress the propagation of T-cells, it is effective for treating certain autoimmune diseases and it's commonly used to treat Crohn’s disease, thus establishing its potential effectiveness for treating MC.
Methotrexate is used in the treatment of cancer, autoimmune diseases such as rheumatoid arthritis, psoriasis, and psoriatic arthritis. It has even been used to induce medical abortions. It works by inhibiting the metabolism of folic acid. It was originally developed as a chemotherapy treatment and it is known to be effective against a number of different types of cancers. At present however, unlike azathioprine, it appears that methotrexate is rarely prescribed to treat microscopic colitis.
In general, since immune system suppressants carry an elevated risk of developing an infection or cancer, this class of drugs should only be considered if all other less risky treatments have been tried and failed to provide relief of symptoms.
Anti-TNF medications
The anti-tumor necrosis factor medications (anti-TNF) such as Embrel (Etanercept), Remicade (Infliximab), and Humira (Adalimumab) are increasingly being prescribed for treating various inflammatory issues, including Crohn’s disease. Because of that, some doctors view them as a possible option for treating microscopic colitis. This class of drugs is a relatively recent development however, and case studies show that while most patients with inflammatory issues may show benefits, a very small percentage of patients experience severe, and even life-threatening adverse events.
The anti-TNF drugs, for example, have recently been linked with an increased risk of a possibly fatal infection with legionella and listeria bacteria, in addition to the long list of pathogens that were previously listed. While they are deemed to be generally safe for most patients, careful consideration should be given before using one of these drugs, because they work by suppressing the immune system, and that can lead to a significantly increased risk of infections and other adverse events.
Surgical Intervention
As a last resort treatment, some gastroenterologists may even recommend an ileostomy in certain severe cases of MC where the patient does not respond to conventional medical treatment methods. An ileostomy diverts the fecal stream into an external pouch, totally bypassing the colon, and thus preempting any opportunity for colonic inflammation, by isolating the colon from the fecal stream. Published case studies show that this surgical procedure will usually bring remission from symptoms. But using such a radical treatment method seems not unlike burning down the barn in order to get rid of the rats, since the colon will no longer provide any functional benefits to the body after the procedure. And if the small intestine is involved in the reactions (and this appears to be the case for many patients), then an ileostomy could not be expected to resolve the reactions that originate in the small intestine.
But the claims that this procedure will always bring remission, are simply not true. There are cases where an ileostomy will not resolve MC symptoms. If an elemental diet, especially if the food is delivered by means of an enteral feeding tube, will not resolve the symptoms, then it would be pointless to pursue a solution by means of an ileostomy because the procedure will almost surely not resolve the diarrhea, nor any of the other symptoms. Therefore, very careful consideration should be given to the details of each individual case before deciding to try this procedure, because it is not a guaranteed cure for microscopic colitis.
Treating Difficult Cases
Some cases are unresponsive to conventional treatments. There can be many reasons for this, but it can be especially problematic when additional autoimmune (AI) diseases are present. There doesn't seem to be any medical research available to either support or disprove this observation, but epidemiological evidence appears to suggest that in cases where various conventional treatments have been tried without success, there is a possibility that one or more issues associated with other AI diseases may be preventing remission of MC symptoms.
Low dose naltrexone
In situations such as this, some patients have been able to resolve their MC symptoms by the use of low-dose naltrexone (LDN). While still in the experimental stages, and not yet accepted by most mainstream medical practitioners, treatments using LDN have established a surprisingly good success rate among many AI diseases that are otherwise refractory to treatment.
This is an off-label treatment for naltrexone, using doses that are only a small fraction of the amount normally prescribed for it's labeled uses. But if taken properly, it is said to reset the immune system nightly, resulting in the suppression of autoimmune-induced inflammation. Since LDN does not appear to be effective for patients who have only MC (and no additional AI diseases), and yet it does seem to be effective at relieving MC symptoms for many patients who also have other AI diseases, it seems likely that LDN may be capable of resolving MC symptoms by virtue of effectively treating other AI issues (other than MC) that have been preventing the remission of MC symptoms, despite a treatment program that would normally be expected to resolve the MC symptoms.
Treating mast cell issues
Most gastroenterologists currently have inadequate training regarding treating mastocytic enterocolitis (if they have even heard of the term previously), so many of them have a minimal working knowledge of ME. Because of that, GI specialists who know how to properly treat the condition may be somewhat difficult to locate. Those who are sufficiently knowledgeable about mast cell issues to understand how to diagnose and treat ME, or other related mast cell issues of the GI tract, typically prescribe either Gastrocrom (cromolyn sodium), or a type 1 or type 2 antihistamine for controlling mast cell symptoms.
Low dose naltrexone
In situations such as this, some patients have been able to resolve their MC symptoms by the use of low-dose naltrexone (LDN). While still in the experimental stages, and not yet accepted by most mainstream medical practitioners, treatments using LDN have established a surprisingly good success rate among many AI diseases that are otherwise refractory to treatment.
This is an off-label treatment for naltrexone, using doses that are only a small fraction of the amount normally prescribed for it's labeled uses. But if taken properly, it is said to reset the immune system nightly, resulting in the suppression of autoimmune-induced inflammation. Since LDN does not appear to be effective for patients who have only MC (and no additional AI diseases), and yet it does seem to be effective at relieving MC symptoms for many patients who also have other AI diseases, it seems likely that LDN may be capable of resolving MC symptoms by virtue of effectively treating other AI issues (other than MC) that have been preventing the remission of MC symptoms, despite a treatment program that would normally be expected to resolve the MC symptoms.
Treating mast cell issues
Most gastroenterologists currently have inadequate training regarding treating mastocytic enterocolitis (if they have even heard of the term previously), so many of them have a minimal working knowledge of ME. Because of that, GI specialists who know how to properly treat the condition may be somewhat difficult to locate. Those who are sufficiently knowledgeable about mast cell issues to understand how to diagnose and treat ME, or other related mast cell issues of the GI tract, typically prescribe either Gastrocrom (cromolyn sodium), or a type 1 or type 2 antihistamine for controlling mast cell symptoms.
1. Ung, K-A., Gillberg, R., Kilander, A., and Abrahamsson, H. (2000). Role of bile acids and bile acid binding agents in patients with collagenous colitis. Gut, 46(1),170–175. http://gut.bmj.com/content/46/2/170.full
Here is a summary of the latest guidelines issued by the American Gastroenterological Association Institute for the medical management of microscopic colitis, published December 18, 2015.
For patients who are symptomatic, the guidelines suggest:
1. Treatment with budesonide is preferred over treatment using other anti-inflammatory medications for inducing clinical remission.
2. When treatment with budesonide is not feasible, treatment with mesalamine, bismuth salicylate, or prednisone is better than no treatment at all.
3. Treatment using a combination of cholestyramine and mesalamine (rather than mesalamine alone), is not recommended.
4. The association specifically does not recommend treatment with probiotics or Boswellia serrata, when attempting to induce clinical remission.
5. For patients whose symptoms relapse when a budesonide treatment regimen is completed, the guidelines recommend continued treatment with budesonide in order to maintain clinical remission.
Additional information can be found in the Medscape article at the following link, and a PDF copy of the original article published by the association can be downloaded from there.
New Guideline Addresses Microscopic Colitis Management
Or, a PDF copy of the original article can be downloaded by clicking this link.
1. Treatment with budesonide is preferred over treatment using other anti-inflammatory medications for inducing clinical remission.
2. When treatment with budesonide is not feasible, treatment with mesalamine, bismuth salicylate, or prednisone is better than no treatment at all.
3. Treatment using a combination of cholestyramine and mesalamine (rather than mesalamine alone), is not recommended.
4. The association specifically does not recommend treatment with probiotics or Boswellia serrata, when attempting to induce clinical remission.
5. For patients whose symptoms relapse when a budesonide treatment regimen is completed, the guidelines recommend continued treatment with budesonide in order to maintain clinical remission.
Additional information can be found in the Medscape article at the following link, and a PDF copy of the original article published by the association can be downloaded from there.
New Guideline Addresses Microscopic Colitis Management
Or, a PDF copy of the original article can be downloaded by clicking this link.
