Melanie Cole, MS (Host): Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole. And joining me today is Dr. Darren Brenner. He's a Professor of Gastroenterology and Hepatology in the Department of Medicine at Northwestern Medicine. In this episode, we're putting constipation into context. We're discussing chronic constipation, risk factors, subtypes, and treatment options for both over-the-counter and prescription medications. We're also discussing the diagnosis and treatment of acute constipation as well as alternative forms.

Dr. Brenner, thank you so much for joining us today. I'd like you to tell us about the prevalence of chronic constipation, some of the risk factors for development and how it really impacts quality of life.

Dr Darren Brenner: Thanks, Melanie, first and foremost for having me. So, part of the reason I thought it was important to talk about chronic constipation is because this is a very common disorder. If you look at multiple prevalence or epidemiologic studies that have really been completed over the last 12 months or so, you see that constipation impacts anywhere between 6 and 11% of the world's population.

So, I always like to put these percentage numbers into perspective. And since we're in football season right now and we're thinking about the playoffs and 70 plus thousand people sitting in a stadium, imagine sitting in one of those seats and looking around. And 1 out of every 9 to about 13 individuals around you suffers from constipation. It doesn't take very long to identify somebody with this disorder.

And I think that the prevalence is high when we look at the risk factors for constipation. And the most common risk factor is age. And obviously, our Baby Boomer generation is getting older. I think as practitioners we're doing a much better job at keeping people alive longer, although some people would argue post COVID those numbers have dropped a little bit. But long and short, people live longer. And so, we're going to see a higher prevalence.

Some of the other most common inducers of constipation include medications, and there are probably a couple hundred medications on their own that induce constipation, including, you know, the things most people think about opioids for pain, benzodiazepines for anxiety, but even multiple medications that treat cardiac disease. Most importantly, if any individual is taking six or more medications at a time, that threshold of six significantly increases the likelihood that somebody will develop this disorder.

Then, we can look at common factors that are modifiable. You know, sedentary lifestyle, not consuming enough fiber, not drinking enough water. All of these are things that we can actually modify or mediate to reduce the prevalence of this disorder specifically. And when it comes to quality of life, we have to look no further than the patients who come in and tell us, "It's not necessarily the symptoms that bother me. It's the fact that I don't know when I'm going to have to go to the bathroom. Or I have to sit on the toilet for an hour or two every morning, so I have to get up at 4 a.m. before I go to work. Or I don't know if I take a trip, if that urge is all of a sudden going to hit me. "So, they don't vacation. They don't go to weddings. They don't go to family events. They do not eat out, and they miss multiple social engagements. And that really kind of brings home how much this disorder can impact a particular individual. In fact, many of my patients often say, "My family, my friends do not understand the burden of this illness." And so, we have to do a better job treating these individuals and their specific symptoms.

Melanie Cole, MS: That's so interesting and you make such good points. And when you talk about quality of life, we typically think of diarrhea. And IBS with diarrhea as something that affects your quality of life in all those ways that you mentioned, and we don't typically think about it for constipation. So, thank you for pointing that out. Now, how are we defining chronic constipation?

Dr Darren Brenner: So, we use specific symptom-based criteria, and there are six. And historically, patients have looked at constipation different from practitioners. We look at frequency. A lot of people come into my office and they say, "I'm constipated because I'm not having a bowel movement every day." And that's actually completely normal. So, we have to eliminate some of these myths and misconceptions. And normal stool frequency ranges anywhere from three times a day to three times a week, and that covers about 95% of the U.S. population.

Then, we look at texture, and we really define constipation, as should be obvious, as hard or lumpy stools. We use something called the Bristol Stool Scale. And a lot of people haven't seen this scale, so to put it into layman's terms, and I apologize to your listeners in advance, but these are individuals who come in and say, "I'm passing things that look like Milk Duds or Baby Ruth Bars." We talk about straining, sensations of incomplete evacuation, a sensation of mechanical obstruction. These are people that come in and say, "It just feels like the stool is sitting at the bottom of my colon and I can't get it out."

And then last one, the one nobody wants to talk about, is the performance of manual maneuvers. Some people have to actually manually disimpact the stool from the rectum, so they have to stick their finger in and pull it out. For some women, they have to splint, which means taking a finger or two, putting them in the vaginal vault and pushing posteriorly, which reduces anatomical changes or anatomical defects. And if individuals meet two of these six criteria, we can define them as having chronic idiopathic constipation.

But the next step is determining what the underlying causes of those constipation are. And we really break this down into four overlapping disorders. And I stress the term overlapping, because the vast majority of the people that I see in clinic have more than one problem. And thus, if we just target one piece of the puzzle, the patient doesn't get better.

So, what are the four categories? The first one is the secondary causes of constipation and this is something we can usually glean from a history and a physical exam. I mentioned before medications, that's a common cause. Endocrinopathies like hypothyroidism or diabetes, hyper or hypocalcemia, neuromyopathic disorders like scleroderma, MS, ALS, Parkinson's. These are all common causes of constipation. And even if one of those is present, we have to look at what we call primary or idiopathic causes, which include irritable bowel syndrome constipation, slow transit constipation, and functional defecation disorders, which means that the stool makes it through the GI tract okay, but the muscles in the pelvic floor do not work appropriately to let the stool out. And again, many of my patients have many of these different disorders playing a role in the development of her or his symptoms.

Melanie Cole, MS: So then, let's talk about medications. I mean, you've just given us some of the subtypes of idiopathic constipation and whether they overlap. And that's really important. And as far as patients and other providers, primary care providers that are seeing these patients on a regular basis, there's over-the-counter and there's prescription. Tell us a little bit about what's going on in the field today as far as medicational intervention.

Dr Darren Brenner: Sure. So, I think that there's consensus and agreement by most people who treat this disorder that the first therapy should be over-the-counter treatments like fiber or osmotic laxatives, PEG 3350. But in normal standard doses, stimulants can be safe as well. It's an old myth or misconception that if you use stimulant laxatives like bisacodyl or senna, that it's going to cause your colon to not function in the long term, or it increases the risk of cancer, and that's absolutely not true. Now, we recently did a systematic review looking at over-the-counter therapies, and it turns out the best three therapies are PEG 3350, senna, and surprisingly or maybe not, fruit. Kiwi specifically has high efficacy for treating constipation, because kiwi contains fiber and antioxidants.

Now, a lot of your listeners and practitioners are going to say, "Well, Darren, what about fiber?" And it comes down to the fact that soluble fiber is going to be significantly more effective than insoluble fiber. But the clinical literature shows that at least in head to head trials, fiber is not more effective than medications like PEG 3350. So, it's not wrong to use fiber, lots of people use fiber, but we certainly start with the over-the-counter therapies. And we recommend one to two good therapies before we go to prescription medications.

In the prescription class, we have multiple drugs that come from a class called secretagogues, including lubiprostone, linaclotide and plecanatide. And there are also prokinetics, the most common one used, prucalopride. There is now even mechanical devices. There is a vibrating capsule that is FDA cleared in the United States that can be used as well. So, there are multiple interventions for patients to consider. The problem is which ones to use first, second, and third line can be very difficult for the standard practitioner.

Melanie Cole, MS: So, you've given us some great information and even some complementary ways to help treat it. But what if they do not work? Then, what is your next step? What do you do?

Dr Darren Brenner: So, a lot of times what I see in patients that present to my clinic is that they start with the over-the-counters, then they try the prescription medications, initially individually, then in combination. And when these fail, there's a concern that the problem is related to motility through the GI tract. And in fact, that is not where we want our colleagues to start their evaluation.

We actually recommend that the first test that's done is a test called anorectal manometry and balloon expulsion testing. And this tests the sensation and the function of the muscles in the pelvic floor. Now, when we think about going to the bathroom, we can break this into three separate categories. Category one is movement. Get the food from the mouth to the rectum, which is the last storage place of stool before it's evacuated. Step two is to get the stool once it's in the rectum to stretch the rectum, which gives the urge to go to the bathroom. And then, step three is opening the muscles of the pelvic floor to get the stool out.

So, the question becomes, why would we start with the muscles in the pelvic floor? And I want your listeners to think of the GI tract like a long tube and a funnel. And we all know that funnels narrow and think that there's a cork in the end of the funnel. If you were to pour laxatives in from the top through the funnel and there was a cork at the bottom, the laxatives are not going to get through, they're going to back up in the GI tract and that's exactly what happens in our body.

So, the first thing we have to be concerned about is the cork. And that cork, which is process three, is made up of skeletal muscles called the external anal sphincter and the puborectalis. And these skeletal muscles are the same as all the other skeletal muscles in the body, the ones that let us smile and nod and wave and walk and throw a ball. So, it would seem pretty counterintuitive if somebody hurt a skeletal muscle like the muscles in their rotator cuff to recommend a laxative. There's not an orthopedic surgeon in the world that would tell somebody with a rotator cuff sprain to take a laxative and rub it on the rotator cuff and it would get better. Well, the same is true of the muscles in the pelvic floor. You cannot use laxatives and thus, the treatment is physical therapy, biofeedback.

So, my recommendations to the listeners is this, if the first two over-the-counter therapies do not work, test the muscles of the pelvic floor. That may be where things end in our bodies, but it's where things start with respects to chronic constipation.

Melanie Cole, MS: That is fascinating and we're learning so much more about pelvic floor physical therapy and the benefits there. So, thank you for telling us about that. Now, there are people that would say psychological effects. We've heard this about constipation over the years. What role does trauma play in the development of constipation? And when we think of trauma, are we thinking of physical trauma or physiological or psychological trauma?

Dr Darren Brenner: These are very good questions. And the question becomes, you know, when it comes to the overlapping comorbidities or psychosocial distress, is it the chicken or the egg? Is it the disorder that causes the distress or the distress that causes the disorder? And I would argue in the setting of chronic constipation, it could be either, but that we shouldn't think of this in a linear sense. But in a cyclic nature, one can cause or worsen the other, which causes or worsens the other, which causes or worsens the other, and you can get at what I'm trying to get at. So, for example, if somebody has chronic constipation, we mentioned earlier, the impact on quality of life, they can't go out, they can't see friends. That can make them dysthymic or depressed, which can make the constipation worse. And worsening constipation can lead to worsening dysthymia and depression, which can make the constipation worse.

But one major trigger we're aware of, and I'm glad you brought it up, is the history of trauma, PTSD, or abuse. And to your point, it can be physical, sexual, or emotional abuse. In fact, while there's a paucity of literature, the literature that is out there says very clearly, if you have a history of physical, sexual, or emotional abuse or trauma, the likelihood of having problems in the pelvic floor is almost ubiquitous, and you should go immediately to pelvic floor testing.

But herein rise the rub. Let's say you have, unfortunately, an individual that was sexually abused, you just can't send them for anorectal manometry balloon expulsion testing, put a catheter in their bottom, blow up a balloon, ask them to go to the bathroom and pass it. They have to understand the process. You must explain this process. Make sure that these patients are comfortable with that process, and then send them or refer them for the specific physiologic testing. So, it can be any type of trauma or abuse, which is why I always beg my colleagues, if you're not comfortable during the first visit because you want to establish rapport, but you can do this in the second visit or so before you send people for diagnostic tests, please, please, please ask about a history of one of these disorders occurring previously in her or his lifetime.

Melanie Cole, MS: That's great advice. Now, we hear about IBS with constipation and/or diarrhea. Can you tell us if the symptoms overlap with chronic idiopathic constipation as we're talking about here today? Because again, IBS is something that we're seeing more and more in younger people and it can come with either. So, tell us what you're seeing as far as that.

Dr Darren Brenner: Sure. Historically, we consider IBS a disorder of youth, teens, 20s, and 30s. Constipation, again, a disorder that we see more commonly as people age, as age is the number one risk factor for the disorder. Now, historically, the way we differentiated irritable bowel syndrome from chronic constipation was by using pain as the mediator. The sine qua non of irritable bowel syndrome is pain. If you do not have pain, you cannot have irritable bowel syndrome.

And as I mentioned earlier, when it comes to chronic constipation, we use those six objective and subjective symptoms, the frequency, texture, straining, incomplete evacuation, et cetera. And nowhere in those criteria do you hear the word pain. However, we know fully and wholeheartedly that individuals with chronic idiopathic constipation have pain. So then, the question becomes, how do we differentiate these two disorders? And many of us would argue that maybe they're not different, but one and the same along a linear spectrum, with pain acting as the mediator. More pain? Irritable bowel syndrome with constipation. Less pain? Chronic constipation. There have been multiple international studies that have shown that 50 plus percent of individuals with constipation have abdominal symptoms like pain, bloating, and discomfort. But more importantly, Alex Ford's team in the UK use artificial intelligence and machine-based learning. And their team asked the computer based on certain algorithms, can you differentiate IBS-C from CIC? And for most of these algorithms, the computer could not. The only way the computer could differentiate between the two is if they built into the algorithm that pain shunted the response to IBS.

And so, what that basically tells us is that these are very much similar individuals. And when a patient comes in, if they don't have abdominal symptoms, that may indicate that we should try one set of medications. And if the abdominal symptoms are there, potentially another set. Because with respects to treating chronic constipation, there is no clinical data suggesting that the over-the-counter medications that we recommend as first-line agents can improve abdominal symptoms like pain, discomfort, and bloating.

Melanie Cole, MS: What an informative podcast this is, Dr. Brenner. As we wrap up, I understand you recently authored a Rome Working Group manuscript on the diagnosis and treatment of acute constipation. I'd like you to summarize our episode here today and what practitioners should know about constipation, what you really want the key takeaways to be.

Dr Darren Brenner: When we talk about the Rome Working Team, this was a group of international experts who were brought together to come up and mediate or modify definition for occasional constipation, what we mentioned earlier as acute constipation. And these are people that don't have the chronic symptoms day in or day out or multiple days a week, but may experience these symptoms intermittently. I think the best example of this is traveler's constipation due to changes in circadian rhythms, alterations in gut microbiome. These are people who never have a problem in their home, but they go on vacation, don't have bowel movements for about seven, eight, nine, ten days and feel miserable. This can be what I like to call the vacation destroyer.

And so, we defined occasional constipation as the presence of at least one of the symptoms we talked about earlier in the absence of alarm signs or symptoms which occur at irregular and infrequent intervals that are bothersome enough to induce a patient to seek medical management. And that medical management can be defined as either self-treatment or consultation with a practitioner. And when we look through all of the literature, what we determined was probably the best treatments for now that people should use for occasional constipation are the same ones that we recommend for chronic, being the osmotic or stimulant medications. We want people to know that they use these intermittently, that they're going to be safe.

So, when we think about constipation, we have to put them in subcontext. Is it an occasional constipation? Is it chronic constipation? People in regular doses can use the over-the-counters. They are very safe, but if they tried one or two, and they're seeing practitioners. Again, the two take-home messages, don't continue to give the medications over and over again. Test their pelvic floors and please ask about a history of trauma or abuse because this portends a very high pretest probability for pelvic floor dysfunction in itself.

Melanie Cole, MS: Thank you so much, Dr. Brenner. That was absolutely a great episode. So much excellent information. You're a very good educator. Thank you very much for joining us and to refer your patient or for more information, please visit our website at breakthroughsforphysicians.nm.org/gastroenterology to get connected with one of our providers.

That concludes this episode of Better Edge, a Northwestern Medicine podcast for physicians. And please always remember to subscribe, rate, and review this podcast and all the other Northwestern Medicine podcasts. Until next time, I'm Melanie Cole.