Constipation: What to Do When Nothing Else Works

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Constipation: What to Do When Nothing Else Works with Dr. Satish Rao

What should you do when you’ve done everything for your constipation but nothing has worked? First, we have to better understand what type of constipation you have, then select from the advanced therapies for your constipation type. These therapies go beyond fiber, probiotics, magnesium, and herbal laxatives.  Today I speak with clinician and researcher Dr. Satish Rao to help you understand how to overcome your constipation once and for all.

Episode Intro

Dr. Michael Ruscio, DC: Hey, everyone, welcome to Dr. Ruscio Radio. This is Dr. Ruscio. I am here today with Dr. Satish Rao, who was on the podcast several months ago. And we did what I thought was a fantastically interesting podcast on SIFO, small intestinal fungal overgrowth. And today Dr. Rao is back to discuss constipation and biofeedback, which is a very interesting therapy, and then if we have time on the tail end of that, talk about some of the medications that are also available to treat constipation. So Satish, welcome back to the show.

[Continue reading below]

Dr. R’s Fast Facts Summary

Constipation and Biofeedback

  • Constipation is not limited to those with infrequent bowel movements. It also includes those who have difficulty passing stool and incomplete evacuation.
  • Different types of constipation
    • Secondary
      • Important to rule out with your GI doctor. Can be dangerous, caused by blockage.
      • Or can be caused secondary to some other conditions: medication side-effect (opiods), diabetes (nerve damage), pregnancy, hypothyroid
    • Primary
      • Subtype 1: IBS constipation
        • Treatment: address IBS and SIBO
      • Subtype 2: Slow transit constipation; caused by underlying muscle or nerve problem
        • Treatment: Medications; prokinetics (Resalor, low dose erythromycin/naltrexone), laxatives (lubiprostone, linaclotide, magnesium, vitamin C, fiber)
        • Female hormone imbalance can also affect this
      • Subtype 3: Dyssynergic
        • Treatment: Biofeedback therapy
      • How to determine your subtype?
        • Ask your gastroenterologist for referral to motility specialist
      • What is dyssynergic constipation?
        • Normally, pressure in abdomen and rectum increases while anal sphincter decreases. In dyssynergic constipation, anal and rectal muscles don’t synchronize. Medications do not often work for this.
      • Who can benefit from biofeedback therapy? Those who
        • Excessively strain, have incomplete evacuation, spend a long period of time on toilet
        • Require enemas
        • Are non-responsive to laxatives
      • How to get help with biofeedback?
        • Physical exam: See doctor for digital rectal examination, using Dr. Rao’s technique
        • Testing: Anal-rectal manometry, or a balloon expulsion test
        • Call a motility center near you, then ask if they offer biofeedback therapy
      • Biofeedback therapy
        • Exercises to retrain your colonic and rectal muscles
        • Reestablish proper control of these muscles
        • Posture, breathing, contraction, and relaxation while using a device that provides feedback
        • A session is about 45 min; 4-6 sessions to achieve correction
        • Covered by insurance
      • Success rate of biofeedback therapy
        • Very effective, around 80%
      • Using a Squatty Potty can also help

Medications for constipation

  • Prucalopride (resalor)
    • Stimulates gut motility via the serotonin receptor
    • 5-1mg for motility/SIBO prevention
    • 2-4mg for constipation
    • Rao feels very safe from cardiovascular perspective
  • Amitiza (lubiprostone)
    • R cites some encouraging research, see transcript
    • Rao comments:
      • Can work well, might be best in older/elderly patients
      • Side effects: nausea and bloating limit its use
    • Linzess (linaclotide)‎, Trulance (plecanatide)
      • Rao finds to be very effective
      • Class of drugs that increase fluid secretion into the intestinal tract to aid bowels
      • Also produce cyclic GMP, which can reduce pain in gut; may take up to 10 weeks for pain effect
      • Works best for those with pain and constipation, and with IBS constipation
      • Risk/side effect: Dr. Rao comments very safe
      • Main side effect: diarrhea (10-20% of patients), might be mitigated if lower dose is used
Constipation: What to Do When Nothing Else Works with Dr. Satish Rao - RusioSatishRao
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In this episode…
Episode Intro … 00:00:42
Biofeedback Therapy … 00:02:12
Constipation Diagnosis Criteria  … 00:08:02
Warning Signs … 00:11:18
Subtypes … 00:14:29
Biofeedback Candidates …  00:21:16
Control Trial … 00:26:20
Therapy Process … 00:27:55
Squatty Potty … 00:31:58
Therapy Success Rate … 00:33:38

Download Episode  (Right click on link and ‘Save As’)

Dr. Satish Rao: Michael, thank you so much. It is a pleasure to be back on the show. I think you have a very eclectic and very interested audience who listens to your show. And I’m really grateful to you in particular for all the service you’re doing to these patients who really have been neglected for a very, very long time. So thanks for having me back. I look forward to our interesting conversation this evening.

DrMR: Well thank you. And of course, yes, it’s a pleasure to have you back on. And I had heard about biofeedback a few times. And it was kind of something that was on my radar screen. I had the intention to look into it once I had time, and sometimes that time never comes around because we’re all busy. But then I had a patient who went and saw someone and had performed biofeedback and really had a pretty powerful experience with it, and so that prompted me to look a little bit deeper. And unbeknownst to me at the time, you‘re one of the, I guess, leading researchers, apparently, in biofeedback. And I think she may have said, or I may have read, that you even were the original developer of that.

Biofeedback Therapy

So can you give us a little bit of context as to what biofeedback is and what your connection with biofeedback has been?

DrSR: Yes, Michael. I think that’s a great segue. We can start with some historical perspectives. So this is in the late 80s and early 90s, where constipation was generally regarded as a disorder of infrequent bowel movements. And so generally the books were written like that. Physicians always perceived constipation as a dysfunction where people don’t go or go irregularly. But slowly it dawned on many of us who were really trying to help these patients that that is not, by itself, constipation. That is just one part of constipation.

Constipation: What to Do When Nothing Else Works with Dr. Satish Rao - constipationAnd over the next few years, if you like, there has been more research to define constipation in a much more heterogeneous manner, so we went on from defining it based on a single symptom, that is infrequent bowel movements, to really engulfing other symptoms, such as excessive straining, a feeling of incomplete evacuation. Some people use digital maneuvers to help bowel movements. Some people have very hard stools. And then it really became clearer, also, that some people actually go several times a day, although they’re constipated. And this was one of the first patients that I encountered, because typically when you ask a patient, “Oh, why are you here,” they say, “Well, I’m constipated.” And then you say, “Okay, how often do you have a bowel movement?” And the patient says, “Oh, somewhere between four to five times a day.” Really? So immediately from a physician perspective the light bulb goes, and they say, “What? This patient must be nuts. How is this possible? The person goes four to five times a day. That must be diarrhea. It cannot be constipation.”

So intriguing as it may sound, that is what is happening, because a patient is not able to completely finish the task of emptying the bowels. And to do so, the unfortunate individual has to go multiple times.

So why is this happening? So that was one of the first intriguing questions that we had to ask. And we had to rely on testing such as anorectal manometry, put a probe with multiple pressure sensors and study the dynamic changes that are happening inside the rectum and inside the anal opening simultaneously to see what was happening. And lo and behold, we found that unlike what happens in normal individuals, where whenever we get an urge, a normal individual gets an urge to have a bowel movement, and we observe what changes take place, they increase the intra-abdominal and rectal push force. Simultaneously, they relax the anal opening muscles.

So this is a normal coordinated behavior that most healthy people do in order to compete a bowel movement. And this is something which is learned or derived during childhood. And then it almost becomes subconscious. And we just carry on like that for the rest of the life never worrying about it until the day when something goes wrong, and this whole pattern of behavior changes. And these folks with this dyssynergic type of constipation, they develop an abnormal pattern. And the pattern may be instead of relaxing the anal muscles, they paradoxically squeeze the anal muscles, or they have lost their push ability. They can’t push at all. In other words, they have lost the whole coordinated mechanism by which they can poop. And this is dyssynergic defecation.

So to answer your question in a long winded manner, this was one of the first things that we learned, that there are many folks who are unable to use their anal and rectal muscles appropriately to synchronize and achieve normal defecation.

Constipation: What to Do When Nothing Else Works with Dr. Satish Rao - AdobeStock111492759WEBgutinfectionIBSSIBO So that was the first pieces of research that we did way back in the 90s, early 90s. Then the question came, “What can we do for these people?” I mean medication is unlikely to work. So some enthusiastic surgeons and so on in the beginning believed in part that this was a spastic problem of the anal rectum. So they thought, “Well, why don’t we give something to relax the anal sphincter muscles?”

And then some enthusiastic surgeons even went ahead giving Botox injections. They thought, “Well, this is a spasm here. How about Botox?” And then some others went on and said, “Well, this is a spasm. We should just cut this muscle.” So they cut the muscle. And lo and behold the Botox didn’t help. And cutting the muscle actually gave one or two people leakage of stool but really did not help the problem. So those are some of the early attempts to try and improve this condition of dyssynergic constipation.

DrMR: I’m really glad that you made the point about constipation not being limited to people who don’t move their bowels, but people who also have incomplete evacuation or straining. And I think it’s important to mention that, because if you’re not inquiring about this with your patients, you may look at, let’s say, a piece of paperwork. And they may check down move my bowels one, two, three times a day, whatever it is. And you may say to yourself, “Well, this person doesn’t have constipation.” But if you inquire in terms of the ease of defecation or the completeness of evacuation or a feeling of incomplete evacuation, then you get the other piece of this.

Constipation Diagnosis Criteria 

And so maybe with that as a transition, can you give us the criteria for how we can diagnose constipation, because I think it partially speaks to that.

DrSR: Right. So as I said at the outset, constipation is a heterogeneous problem. And there are various types, at least that’s how I look upon it. There is the acute constipation, which is rare, but we all suffer with it in a milder form in travel, stress, varying eating habits, and so on. We all find that our bowel habits become a little irregular. That’s normal for all of us. Then there are some individuals where there’s actually a true blockage in the colon, or they get impaction in the colon, or they have a major pathology like a colon cancer that truly stops movement of stool all together. That’s acute, which I think is rare, but yet it’s a serious problem.

Most of the time when we report constipation, it is really the more chronic constipation. And there I tend to look at it as two major categories. There is the secondary constipation, which can be because of medication, for example, opioids. There is a big talk about it throughout the country now. And one of the sad, serious adverse effects of opioids is on the gut motility. And constipation and gas and bloating are the big problems there, then diabetes and metabolic conditions, like thyroid disease, pregnancy. Over 25, 30 percent of women become constipated during pregnancy. Neurological conditions, such as strokes or multiple sclerosis, muscle disorders, all of these actually lead to constipation. And in those situations, really correcting the underlying problem leads to improvement in bowel function.

If there is no secondary cause, if none of these and others that I mentioned are causing it, then you’re left with what I call the primary constipation, which is primarily a dysfunction of the colon nerves and muscles. And in this primary group I look upon it as three major subgroups.

“…we found in several studies that nearly two thirds of patients who have a problem in the pelvic floor also have core existing slow transit constipation.”Constipation: What to Do When Nothing Else Works with Dr. Satish Rao - tweet e1540485375388

There is the irritable bowel syndrome with constipation, and these are folks who have abdominal discomfort or pain with an altered bowel habit and some harder stools and difficult to pass stools. Then we have the group which we call slow transit constipation. And these are individuals in whom there is an underlying muscle or nerve problem, where the colon innately is unable to push and move stools in an orderly regularized fashion. And then you have the third group that is the dyssynergic constipation group, where there clearly is a problem with evacuation of stool.

So in terms of the treatment and so on, you really want to tailor the treatment based on the underlying subtype. If it is more a question of slow transit constipation or an irritable bowel syndrome with constipation, then medications to improve discomfort and pain and medications to stimulate the colon or medications to increase fluid content in the colon are all effective. But if it is one of a pelvic floor dysfunction or dissynergy or coordinated muscle function, then biofeedback would be the way to go.

Warning Signs

DrMR: Now are these things that you find most gastroenterologists are taking into account in terms of trying to establish a subtype and then steering the medication or therapeutic recommendation based upon that, or is it more so “Let’s try this drug because it’s oftentimes used and see how you do? And then if you don’t respond well to that we’ll move on to the next one.”

And I know it’s asking you to paint with a broad brush and make kind of a generalization, but just for the patients who may be thinking about checking back in with their GI doctor and having their feelers out for if their GI doctor is giving them a high level of care or maybe not quite as robust level of care, would you expect most GIs to be looking at it in this light? Or are there some warning signs patients should be looking out for?

DrSR: I think that’s a great question, Michael. Unfortunately, most GIs are not looking at constipation in this manner, which is a little sad. They look at many things in a systematic manner, but this is one of the conditions where I don’t believe they are looking at it like this. And the usual approach they take is when one complains of constipation, they want to ensure that there is no major colonic obstructive pathology. So they do a colonoscopy, if you like, or they may do a CT scan, or one of the two. If it is not there, they will then try either OTC compounds, PEG laxatives, etc., or they may use one of the newer compounds. And if they don’t work, they may then consider referral to a specialist, a motility specialist such as myself.

Constipation: What to Do When Nothing Else Works with Dr. Satish Rao - AdobeStock163293447WEBdoctorpatienthealthpinkbluelaptopstethoscopeWhat I would do — you asked a very important question there — is really from a patient perspective as well. I don’t think this approach that my colleagues are using is wrong. I think it’s fair. They may not have the technical expertise or the availability. But, what I would ask them to do is not to give up. If their symptoms are not responding, then to please go back to their doctors and ask them to be referred to a specialist. They have to take this — because unfortunately, as we discussed in the previous talk as well, constipation is more a life altering situation, a quality of life issue. It’s a nuisance. It’s not a life threatening problem.

So physicians, in their rush of things, tend to be very dismissive of this problem. And so unless the patients really take some initiative and say, “Look, I need to get to the bottom of this problem, I need more help,” it’s only then they’ll likely get the help. These guys know where to send them, but they just need to take the little extra step either to do it by themselves or get them more help.

DrMR: Gotcha. That makes sense. So people might see their GI, have a more acute dangerous pathology ruled out, and maybe they try a therapy or two along the way. And then if they’re not getting the results that they’re looking for, then they would ask for a referral to a motility specialist, correct?

DrSR: That would be the right approach, I think, for their management.


DrMR: Okay, so then coming back to the subtypes, there were the three: the IBS subtype, the second subtype, which had slow transit and maybe an underlying muscle or nerve problem, and then the third subtype being dyssynergic.

I think many of the people listening or reading this are familiar with some of the treatments for IBS and for SIBO, because we talked about that quite a bit on the podcast. But looking at subtype two and three, how do these two differ, because if the slow transit type constipation has underlying muscle and nerve pathology, how do people distinguish or how do you as a clinician distinguish between the two, because it seems that they have a lot of overlap, because if dyssynergic, as you mentioned, is that lack of pressure in the cavity combined with poor or overcontraction of the anal sphincter, that seems like it has overlap with the slow transit type. So can you clarify the delineation between those two?

DrSR: Very good. I think you really hit on a very important point as well there. So there is a significant overlap between the outlet constipation, or the dyssynergic type of constipation, and the slow transit constipation, because you can imagine if we are not emptying stool because the outlet is blocked or incoordinated, you will secondarily also retain stool further upstream. It’s bound to happen.

Constipation: What to Do When Nothing Else Works with Dr. Satish Rao - AdobeStock106220231WEBstomachgutAnd we found in several studies that nearly two thirds of patients who have a problem in the pelvic floor also have core existing slow transit constipation. But when we treat the pelvic floor problem, their slow transit constipation will get better. I mean it follows once their pelvic floor gets better, things are moving, automatically the slowing, which is the secondary problem, improves. But then there are the other group of patients in whom the primary problem is one of muscles and nerves.

So two things to bring in, there are some important pacemaker cells inside the colon. These are called the interstitial cells of Cajal. These kind of pacemaker cells are either absent or deficient or damaged in patients with the slow transit constipation. That’s one thing we have learned through very systematic research. This is all to do with the slow transit group. And the other thing we have learned, this tends to be more common in women and less common in men. And there’s one piece of research that showed — and that may be because these women tend to have a higher amount of progesterone receptors on the colonic smooth muscle, and because of that the progesterone receptors get activated. And they tend to kind of paralyze that smooth muscle in the colon, making the colon more sluggish. And the third just final point of the slow transit team is some of the work that myself and Mark Pimentel have been doing in the last ten years, has been looking at this methane story. And I think you’ve talked to Mark on this, I believe, some times.

And so we found that methane is a gas that is produced by about a third of the population by a special bacteria which is in the colon. And this methane gas — and Mark showed this in very nice studies — that when you profuse, in animal models and so on, it actually slows motility. So we have shown, also, that in patients who have more difficult, more refractory constipation, they tend to produce methane. And these are often also folks who have more difficult, more challenging constipation. So methane, progesterone receptors, and lack of the nerve pacemaker cells are all components that lead to slow transit constipation.

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Okay, back to the show.

DrMR: You make many great points, but one thing in particular that sticks out for me that I think might be important for the audience to be aware of is the connection between digestive health and female hormones and female hormone imbalances.

One of the things that I have seen, a certain kind of patient type, I guess you could say, a patient subtype, is a woman who co-presents with digestive symptoms who also has clear signs of female hormone imbalances. And that might be a cycling or a non-cycling woman, but it might be a regular cycle length or menstrual flow or cycle irregularity or pretty marked PMS symptoms. And when treating their gut ailment, we oftentimes use herbal medicines that help to balance female hormones. When using both of those therapies together, I’ve seen people respond very, very nicely to that. And I first keyed in on that because of course you’ll hear some women say, “My bloating, my gas, my constipation, all my gut symptoms wax and wane throughout different parts of my cycle.” So clearly I always observed this relationship between the two. And there are a few mechanisms there. I didn’t know about the progesterone receptors in the colon, as you mentioned, and so that further connects, mechanistically, those dots.

So for those listening, definitely consider looking into balancing your female hormones if you have digestive symptoms that seem to wax and wane as you go into different parts of your cycle or if your GI symptoms got much worse when you went into the menopausal transition.

DrSR: I would echo that. I think that’s a great recommendation to the listeners.

Biofeedback Candidates

DrMR: So Satish, let’s talk a little bit more now about the biofeedback therapy. And I think we’ve partially outlined the type of patient that this will work for. So I guess let me ask you in two parts: one, if there’s anything additional you’d like to offer the audience in terms of what someone might look like who is a good candidate for biofeedback, let’s have you offer any additional information there. And then, let’s go into what the biofeedback therapy looks like.

DrSR: Two very good questions. First of all, really, in terms of recognizing the symptoms, it is often hard. But these are often individuals who are spending a lot of time on the toilet trying to pass stools. Often they’re excessively straining. Or they’re left with a feeling of incomplete evacuation, because eventually a small number stool will come through, but the rest of the stool inadvertently has been pushed back. And then they get up, go. An hour or two later they may get the urge again because the stool has come down. And then they’ll attempt again, either successfully or unsuccessfully.

So when someone has this kind of behavior of multiple attempts to empty, or they’re straining excessively, or they’re left with a feeling of incomplete evacuation, or they are being forced to use some form of digital assistance maneuvers — there are a number of these. Some people just push on their bottom or in their perineal region. Some actually have to push in the vagina, which is called vaginal splinting, to try and support the vagina to facilitate the bowel movement. There are others who physically have to remove stool in a regular manner.

Constipation: What to Do When Nothing Else Works with Dr. Satish Rao - laxativesSo if patients are experiencing any of these, and more importantly people have gone and told their doctor, “Doctor, I’m constipated,” and the doctor has given them treatment, and they’ve tried laxatives, and they’re finding that sometimes laxatives are either making their symptoms worse or in spite of laxatives they’re having these symptoms, if they are having any of those, then it raises a high index of suspicion for dyssynergy.

DrMR: And that last point was if they’ve been non-responsive to laxatives, is that what you said?

DrSR: Yes, please, very important.

DrMR: Would someone who misses a day or two days or three days, and then they have a nice evacuation, would that person be less so a candidate for biofeedback?

DrSR: Normal bowel habit patterns seem to vary enormously. And I think people have tried to define this as anything like three times a day to three times a week. So having a bowel movement every other day or sometimes every third day may be normal for some individuals. And as long as they’re not bothered by it, it is not affecting them in any way, I would not even worry about it. But for some individuals who have had a bowel movement daily or every other day, and suddenly they’re finding that they’re now going two, three days or four days without a bowel movement, then there is a problem. A change in bowel habit is an important problem. So I wouldn’t worry if the individual is already having, as you described a person there, every third day, but doesn’t have any other symptoms, has a normal bowel movement, feels completely empty, well that’s normal for that individual. They don’t need to do anything.

DrMR: Gotcha.

DrSR: So I think with regards to diagnosis, I think one of the important things that we have shown through studies is a good digital rectal examination on the bedside can provide useful information. And we did a prospective study to show that at least my digital rectal examination has a 75 percent sensitivity and about an 87 percent specificity. And I did find dyssynergy when we compared with standard testing. Now I do it in a very systematic, meticulous manner, so I don’t expect all my colleagues to do it that way. The point I was trying to get across is that one can identify dyssynergy at the bed.

DrMR: And so you have a specific technique for the digital rectal exam that is maybe a bit more accurate than the norm?

DrSR: No, I think it’s just using the normal techniques. But people don’t take the time to do it. But yes, I think I do use a couple of techniques that I use. Also, in simple terms, with the finger inside the rectum, I place another hand on the patient’s abdomen. And then I have them push and bear down as if they’re attempting to poop. And I’m looking for three important changes.

One, I’m looking for the hand over the abdomen to feel tightening of the belly muscles. In other words, they’re developing good push force. Then I would expect the finger to kind of gently move out by about half an inch to an inch, which tells me there’s a good push force, and there is perineal descent. And the third important thing is the external anal sphincter muscle and the puborectalis muscle both relax in tandem. If these three features are present, it is unlikely that a patient has dyssynergy, and there’s a normal pattern of emptying. But if two of these three features are not present, then at the bedside one should suspect dyssynergy.

Control Trial

You mentioned your studies. And I’m not sure if you’ve done a few, but the one I’m looking at here in front of me is entitled “Long Term Efficacy of Biofeedback Therapy for Dyssynergic Defecation: A Randomized Controlled Trial.”

Constipation: What to Do When Nothing Else Works with Dr. Satish Rao - 20179692DrSR: Sure, we’ll talk about that. I was just telling you about the diagnostic testings, if I may just finish on that. So the more definitive test of demonstrating this is through anorectal manometry. The reason I say that is patients usually feel a little inhibited. They may not relax appropriately if they’ve got somebody’s finger in their butt and so on. Imagine how that might feel! Manometry on the other hand is much more accurate. And we can define the dyssynergy. There are multiple patterns of dyssynergy that we have defined now. So you can actually see whether it’s the rectal pusher that’s not working or the anal relaxation that’s not working or the paradoxical contraction that’s happening. And the other third supplementary test is a balloon expulsion test. So we place a simple water filled balloon in the rectum, give the patient privacy. We walk away. And they have a timer clock. They have to expel this balloon. And normal individuals can expel a balloon filled with 50 mL of water in less than a minute. Patients with dyssynergy will have difficulty or will fail to expel the balloon. So these three things, the rectal exam, the anorectal manometry, and balloon expulsion test really are complementary, and they will help us to definitively diagnose dyssynergy.

Therapy Process

DrMR: Okay, so that would be step one. And then if they are diagnosed, what does the therapy look like? And also, where can people go to obtain this therapy, because I know this is not something that’s offered in every GI doctor’s office. But I think there are a handful of centers that offer this. So can you tell us more about that?

DrSR: Right. The good news is there are more centers now offering treatment than they were even five years ago. And I think it’s slowly becoming more popular. For example, we are running workshops, constantly training. I run two workshops a year or so. People come from all the country and learn. I quite often encourage physician nurses, physical therapists, and so on to come. And it’s being offered in multiple settings.

Physical therapy’s one common setting in many cities in the country, or motility centers. And the American Neurogastroenterology and Motility Society has a nice website, and it has a registry which is a state-based registry of motility centers in each state and cities. People can go take a look. Someone in Los Angeles can look up and see oh, what are all the centers doing motility studies? And if they call them they will be able to tell them whether this facility or this treatment modality is available. So I think they are now available in many, many places.

DrMR: So just find the motility center closest to you, call them and ask if they offer biofeedback therapy.

Constipation: What to Do When Nothing Else Works with Dr. Satish Rao - AdobeStock50037472WebgutstomachinfectionIBSceliacDrSR: Perfect. And if they don’t, they will be able to tell them where they can find the treatment also. So usually that is the best way to go about it. And in terms of the treatment itself, briefly, the whole goal of biofeedback therapy is to retrain the pelvic muscles to perform a coordinated function. And we use the biofeedback techniques because these muscles are deep inside. People can’t see the muscles. And the muscles have become dysfunctional over time. So in order for them to connect with their muscles, we need to put something close to the muscle, a device. And here we put a pressure probe or an EMG device. And then we have them perform an act, like squeeze or push or bear down. And when they do those maneuvers, they can see on a monitor display what are the muscle changes happening. And they can see for themselves that oh, this is what I’m supposed to see. I’m supposed to see a rise in pressure at one end. I’m supposed to see a drop in pressure at the opening end. And in fact what I’m doing is I’m doing the opposite. Instead of dropping, I’m going up. So that visual display to the individual immediately connects with what is happening inside their body.

So the whole goal of this biofeedback is to, number one, connect the patient with their bodily dysfunction. And once they are connected with the bodily dysfunction, then to use a number of techniques such as diaphragmatic breathing techniques, posture, how to sit, and how to push not in an excessive manner but in a coordinated manner as they’re pushing, to watch this display and use the feedback that they are receiving both on the monitor as well as by the nurses or physicians who are there helping them, to use all of this information to correct the behavior. And these treatment sessions usually take about 45 minutes at our place to an hour. It takes between four to six sessions of this treatment for them to completely correct their behavior.

DrMR: That’s not actually too bad, four to six sessions.

DrSR: No, not at all, actually. And the good news is most insurance places now reimburse it. I mean in the earlier times it was very tough. But Blue Cross Blue Shield and Aetna and United and many of them actually, thank God, but they do cover this biofeedback treatment. So I think it should be more widely available, and people should use this technology. And remember, dyssynergy affects about a third of the patients with chronic constipation. So there are millions with this condition in our country.

Squatty Potty

DrMR: Satish, do you find those kind of Squatty Potty little stools that you put underneath your feet, is that something that may make sense for this population of people to use as an at home adjunct?

Constipation: What to Do When Nothing Else Works with Dr. Satish Rao - squatty pottyDrSR: Absolutely, absolutely. I think the Squatty Potty is really a very smart invention. I’ve been using the Squatty Potty kind of device for a very long time, because when we started this biofeedback in the early 90s, I was looking around for a Squatty Potty. There was nothing around. So I went to our daughter’s piano recital. Our older daughter, she was about six or seven, she was a tiny, petite young lady. And so her piano teacher, they wanted this little girl to sit erect. But if she sat erect she could barely reach the piano and everything else. So she had to keep stools under her legs to keep her body erect and raise the stool and everything. I said, “Wow, these little piano stools are interesting. I want to get them,” the multi-tiered, multi-layered piano stools. I ordered them from a guy who was making it in Chicago in a garage for my biofeedback treatment.

So in a step up manner, based on the height of the individual patient, we could then put these piano stools under their feet to get them to the right angle and level that they need to push. So Squatty Potty really is a very nice invention. I’m very supportive of those guys. And I think I would recommend this to anybody listening to try and use this. Sometimes they may have very subtle mild dyssynergy that they may be able to quickly correct without the need for medical intervention. So it’s a great thing.

Therapy Success Rate

DrMR: And then what would you estimate the success rate of biofeedback therapy is?

DrSR: So there have been several randomized control trials. And you just mentioned one, which was long-term, which was part of our study, where the National Institutes of Health supported us for a randomized control trial where we compared standard therapy, which is just laxatives, with biofeedback therapy of six sessions, like I just mentioned, with a third group, where we did a sham treatment, where we brought the patients in. They all had dyssynergy. We placed a probe inside their rectum, but we did not teach them anything else. But instead we played them some relaxation tapes and so on.

Constipation: What to Do When Nothing Else Works with Dr. Satish Rao - AdobeStock38603583WEBgutbacteriastomachelementaldietprobioticsAnd we showed that biofeedback was very, very effective. Eighty percent or so patients got corrected. So in terms of the success in our lab, we have 80 percent success rate with biofeedback in correcting dyssynergy. The group 20 percent failure is largely because of individuals not complying with it. There are some other issues that really make it harder for them. And some of them have overlapping slow transit constipation. And they really run into trouble with that. But 80 percent of patients do get better with biofeedback therapy

DrMR: That’s impressive, yeah. I think we’ve gone through a pretty good narrative on biofeedback. I did want to transition to just a couple of the medications and get your take on some of those. But before we leave the topic of biofeedback, anything else that you’d like to offer people?

DrSR: Just a couple of final thoughts. I think it is quite unlike any other treatment. Most patients would want us as physicians to fix their problem. And this is one where really there is active patient participation. This is a problem which is innate to their body and their muscles and so on. So please don’t expect the physician or the nurse or the therapist to fix the problem. This is a treatment where we are all co-partners in helping you. So this is a combined treatment program. So we help, and they have to do their part practicing the exercises at home and really working with us. So that, I think, is one of the first things. So the expectations have to be different. And they have to remember that they have to practice this for a very, very long time. Short-term practice is not going to be really curative in this problem.

The second part is, in addition to the muscle training that is mostly what we discussed, there’s another component that some individuals have a sensory dysfunction, where the muscles may get corrected. They know how to correct everything, but they’re not feeling stool. And they have a sensory dysfunction in the rectum. And they need a separate biofeedback, which is called sensory biofeedback training. And through that you can really fix that sensory dysfunction as well. So those are the points I wanted to get across.

Resolor Usage

DrMR: Gotcha. That’s great, great points. So now there’s this subtype of people, subtype two as you mentioned earlier, that may benefit from certain medications. And I’m assuming many of the people listening to this or reading this are familiar with prucalopride, also known as Resolor. And from the research I’ve seen, and I believe there was a systematic review with meta-analysis that compared different, using the term loosely, laxative or prokinetic-type medications. And I believe it was looking at prokinetics for constipation in this systematic review with meta-analysis. But it showed that Resolor was the most effective out of all the agents that have been used. And so that’s definitely one that comes up. So why don’t we start the dialogue there.

And something I’ll just offer as fodder for the dialogue on this, there’s maybe two different ways it can be dosed. And I’d be curious to get your thoughts on this, Satish, more so as a prokinetic for preventing SIBO relapse, maybe being used at .5 milligrams up to about 1 milligram a day. And then it can be used at a higher dose, around 2ish milligrams per day, more to be used to directly treat the constipation. It’s not something I use a lot, so I can’t speak to it very in depth, although we have advised a handful of patients on it. And for some it’s been helpful. So what are your thoughts on Resolor?

Constipation: What to Do When Nothing Else Works with Dr. Satish Rao - seartoninDrSR: So great thought. So first of all, prucalopride is a serotonin compound. Serotonin’s a very important neurotransmitter and a hormone that we produce in the gut. About 80, 90 percent of serotonin is in the gut. And it is a very important regulator of peristalsis, depending on which serotonin receptor the serotonin works. But prucalopride specifically works on serotonin type four receptor. And there it stimulates gut movement and gut peristalsis. So that is the mechanism by which it works.

And you rightly said that dosing this drug for the right indication is going to be very critical. And again, like you, I use very small doses, half or maybe one milligram in patients with small bowel dysfunction or patients with small intestinal bacterial overgrowth scenario. But in patients with constipation, I often really begin with two milligrams a day for them, once a day. And if that is too much, I will back it off to one milligram.

Or if that is too little, then I will even go up to four milligrams a day. And that still is quite good. So my range is between .5 milligrams to four milligrams, depending on the conditions and depending on the effect. Generally a very good drug, very safe from a cardiovascular perspective, because that’s been one of the concerns of this whole class of drugs. This one has proved to be very safe so far. Nausea, really, and some headache, I think, are the two major concerns for this drug. But otherwise it’s a very good drug.

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Lupiprostone Usage

Constipation: What to Do When Nothing Else Works with Dr. Satish Rao - 28410406DrMR: Now there’ve been a couple other drugs, most notably lubiprostone, or people may know this as Amitiza. There’ve been two studies that have come onto my radar screen lately. One, the study title is “Lubiprostone Improves Intestinal Permeability in Humans: A Novel Therapy for the Leaky Gut, a Prospective Randomized Pilot Study in Healthy Volunteers.” I’ll put the link in the show notes. But essentially this study induced leaky gut via NSAID use, Tylenol, ibuprofen. And all the subjects were given NSAIDs, non-steroidal anti-inflammatory drugs, which can irritate the gut, in attempts to induce leaky gut. Half of the group was also given lubiprostone. And they monitored leaky gut via the lactulose/mannitol test. And they showed that lubiprostone was able to prevent leaky gut.

Constipation: What to Do When Nothing Else Works with Dr. Satish Rao - 27650225Now there was another study entitled “Lubiprostone Accelerates Intestinal Transit and Alleviates SIBO in Patients with Chronic Constipation.” And they showed that lubiprostone can alleviate SIBO. Now some of this may be because the methane overgrowth and slow transit kind of feed each other. And there’s been some discussion that if you can treat the transit, even with something like magnesium, or there was one study looking at senna, they showed a decrease in the levels of methane gas. And this may be because if things hang out in the intestines for too long, it feeds these Archaea, or these bugs that secrete methane gas, which further slows down transit. It’s kind of this self-feeding cycle.

So one of the ways to potentially unwind that cycle is by using agents that help with laxation or with motility. And that may be why we see the positive benefit with lubiprostone in small intestinal bacterial overgrowth. But it’s because of these two studies that I’ve been more interested in lubiprostone, aka Amitiza.

And so, Satish, I’m curious to get your thoughts on is there a certain presentation type that may best lend itself to using lubiprostone? And we kind of alluded to that earlier. But I’m more so wondering for a patient who’s got maybe a consolation of symptoms or a certain presentation or a doctor listening to this who’s maybe not a GI specialist, are there certain broad characteristics that make you lean more favorably to lubiprostone with your patients?

DrSR: So a good question. As you know, lubiprostone has been with us for about 10, 12 years, a lot of experience over the years with this compound. It is a good drug. It works in a sizable number of patients. But the major challenge that I have faced over the years is really the side effects, particularly with nausea and bloating, which has limited its use in many of my constipated patients over time, which we don’t seem to see now with some of the newer compounds. Having said that, my personal experience has been that lubiprostone works very well in older patients. I have found tremendous success in elderly constipated individuals, lubiprostone, much more than younger people. The older folks also don’t seem to get the nausea and the other side effects we see with younger people. And I don’t know why. I don’t have a good explanation for it. So that’s where I tend to reserve its use, to a large extent, because now with the other compounds that are now available, I tend to use some of the newer ones.

Very quickly with regards to the permeability, I think it is a very interesting drug because it’s a chloride channel two activating drug. It has been shown to have some effects, very favorable effects, in altering intestinal permeability. And probably what it does is it really reverses the permeability mechanics of ion exchange and so on in the gut. And thereby it stops things leaking. And there may be other effects of this compound that we haven’t fully realized.

Constipation: What to Do When Nothing Else Works with Dr. Satish Rao - leakygutI’m very intrigued by this recent healthy volunteer study that you just mentioned. It’ll be nice to take individuals with a leaky gut and then see what happens to them. I look forward to that follow up study.

DrMR: Yeah, same here, absolutely. And it’s interesting that you mention the side effects, because one of the side effects I’ve heard can be problematic for people using lubiprostone, also is it’s hard to find the right dose in terms of if they take too much or they have a bit of an off day, they go from constipation to diarrhea. And it makes them a little bit gun shy about using the lubiprostone. Have you found that to be one of the more common side effects also?

DrSR: Yes, I think the diarrhea has not been as common as I’ve experienced. It is there, but in those where they get it, it’s very hard to find the right dose. Initially it was really a bigger challenge for us because the original approved dose was 24 micrograms. That was for constipation. But subsequently two years later they got an approval at the eight microgram dose for IBS with constipation. And that really helped us, because now we could titer the dose much better. Somebody may need just eight in the morning and 24 at night, so you have a 32 microgram dose individual, whereas previously they either had to go between 24 and 48 or just stay with 24. So we have the titrating ability. With that, I’ve not found that to be a bigger problem.

New Class of Drugs

DrMR: Gotcha. That makes sense. Now what are some of your other drugs that you find to be helpful for constipation?

DrSR: So I think the two other drugs that are now FDA approved, one is linaclotide. And I’ve found that to be very useful and helpful. It works through a different mechanism of action. It works on the guanylate cyclase mechanism. Lubiprostone, linaclotide, and plecanatide, they are a brand new class of drugs where they work by increasing fluid secretion, particularly chloride secretion, inside the gut lumen. They act through slightly different mechanisms, but ultimately the net effect is to increase fluid inside the lumen. And once you build up excess amount of fluid in the intestine and lumen, the wall distends, and secondarily the gut contracts and tries to push the fluid and any of its contents out. And that is how these drugs primarily work. So that, I think, has been an interesting mechanism by which both linaclotide and lubiprostone work.

But linaclotide and plecanatide seem to have another distinct effect, where in addition to the laxation effect, they produce a compound called cyclic GMP. And this cyclic GMP has been shown in animal models to get absorbed and numb the nerves in the gut. So these drugs seem to have a dual effect. They seem to have a constipation relieving effect, or a laxation effect. They also seem to have a pain relieving effect, or analgesic, visceral analgesic effect, which is quite interesting, which we didn’t know in the beginning, but we kind of saw.

Interestingly, I was one of the lead authors of the linaclotide paper. And what we saw was the laxation effect happens very quickly. You’re talking about within two to three weeks, or four weeks, you see the effect. The bowel movements get softer. They get easier. Pain doesn’t get better that quickly. Pain takes between six to ten weeks to get better. So it’s a slightly slower onset. It’s a slightly different mechanism of action. And I think that’s what we learned from the studies. And very likely plecanatide, which is currently only approved for chronic constipation, may also show a similar effect. So these drugs have a slight advantage in the sense that they may not only improve constipation, but they may also improve abdominal pain, discomfort, and even bloating, to a large extent, unlike some of the traditional laxatives, such as PEG and Miralax and even lubiprostone.

Constipation: What to Do When Nothing Else Works with Dr. Satish Rao - constipationgutpainDrMR: So then my next question being, who do you think this works best for? Clearly someone with constipation and with pain, but would you enhance the patient subtype that you think best fits a prescription for linaclotide?

DrSR: So in a patient with chronic constipation, particularly the slow transit constipation group, or a patient with irritable bowel syndrome with constipation, I think those two groups I would definitely consider either linaclotide or plecanatide as my first drugs of choice now. There are some issues with it.

I mean these drugs, again, they’re all designed to work in the gut only. They have very little systemic absorption. So they have very low drug-drug interactions. They have low, virtually no effects on the liver or the kidneys. And so they’re very, very safe from that perspective. And people taking all other medications, it doesn’t really affect it. So it’s very safe from that perspective. So if they’re not working, then I think we may have to go with other compounds. But those are the three that I use, linaclotide, plecanatide, or lubiprostone are my first drugs of choice now.

Common Side-effects

DrMR: Okay, and so very safe like you said. Are there some more common side effects for people to be on the lookout for?

DrSR: So the main side effect with linaclotide has been diarrhea. And in the clinical trials it was seen in about 18, 19 percent of patients. And in clinical practice, too, we see it in at least 10, 15 percent of patients. What has been good about that is, I mean there were two doses that were available, the 290 microgram dose, which is a dose that is approved for IBS constipation patients, then the 145 microgram dose that is approved for chronic constipation patients. Some patients, for reasons unclear, they will get quick diarrhea. So fortunately, just recently, the FDA approved, about a couple of months ago, the 72 microgram dose, which has been a lifesaver, because now we can give the smaller dose. And we can get the beneficial effect for these patients without the adverse effects. So that, I think, has been a plus.

Constipation: What to Do When Nothing Else Works with Dr. Satish Rao - AdobeStock76635780WEBgutibsSIBOdiarrheaPlecanatide, interestingly enough, in the clinical trials, they showed a lower incidence of diarrhea. Their reported diarrhea incidence is five percent as opposed to the 18 percent or so that we saw with linaclotide. So they have a lower incident of side effects. And they claim that that’s because it’s a slightly different molecule, although it acts similarly, like a guanylate cyclase agonist. So that may be a plus for plecanatide. Time will tell. We’ll see how it falls in clinical practice.

DrMR: Well I think you’ve provided us with some great tips and insights. And for the people listening who are maybe more accustomed to the natural therapies, certainly that’s, I think, both of our preferences, but I think we both realize that there’s not always going to be an herbal or dietary or vitamin based therapy that’s going to work for people. So it’s important to be open-minded to the medications when they’re needed and try to find the safest medication, and also find the patient population or presentation that the medication best fits so as to be able to make a recommendation that has the least probability of side effect or harm to the patient.

DrSR: Absolutely. I couldn’t agree more. I couldn’t agree more.

DrMR: Is there anything else that you want to offer before we bring the conversation to a close?


Constipation: What to Do When Nothing Else Works with Dr. Satish Rao - high fiber foodDrSR: I just wanted to mention one of the things that people always talk about is fiber. And fiber has been tooted for a long time as being very beneficial. And no question, I think it does help a proportion of patients. But it is important to remember that fiber can be a plus or a minus. And we’ve done some interesting studies with plums showing that plums actually work, or prune juice, prunes, really, rather than prune juice. In a randomized study we found that to be helpful, and likewise a compound that comes out of where you live, Michael, made by the California Sunsweets group, called super fiber, interesting fiber compound. We did a randomized control study and published it maybe a couple of years ago showing that this fiber is an interesting fiber, because it’s a mixed soluble and insoluble fiber, unlike bran or unlike regular fiber. It’s all natural, made from plums and pomegranate and acacia and so on. And these are some things that can be useful in more simple constipation. But really, once you develop more chronic constipation, then I think you have to go towards what we talked about, linaclotide, plecanatide, lubiprostone, or biofeedback therapy, depending on the subtypes. So sometimes the simple remedies may also be helpful.

Episode Wrap Up

DrMR: Absolutely. And I think that’s a great way to kind of bring the conversation to a close. And for people listening, remember to start with the basics. This is definitely a discussion, I think, that’s more geared towards someone who’s gone through the basics, and now they’re kind of struggling for what the next step should be. And I’m hoping it’s really going to help the people who feel a little bit divided, meaning they want to be proactive in their health care. They’re willing to change their diet, use probiotics, take magnesium, take fiber, but they’re still not getting the result. And maybe their philosophical allegiance is more so to natural medicine, and they feel a little bit guilty or a little bit dissident about using a medication. I’m hoping that this conversation will help people realize that just because you’re using a medication, it doesn’t necessarily mean that you’re doing something bad or harmful. And hopefully by understanding some of the available drugs, it will be less of a fear of the unknown sort of endeavor. And you can go into this decision with a little bit more information.

Constipation: What to Do When Nothing Else Works with Dr. Satish Rao - fmf probioticsDrSR: Right. I agree. And I think we covered a lot of ground today, ranging from simple treatments to more prescription based treatments, even those that are available in our country and those that are not available. And more importantly, I think, Michael, we had a very nice discussion on this whole concept of dyssynergic constipation and biofeedback therapy, which really I think you’ve done a human service by bringing this to light to the many listeners of your podcast.

DrMR: And thank you for giving me something to bring to them. So a hearty hats off to you. And thank you so much. I’m continually impressed by your work. I have to say that between SIFO and the work with biofeedback, just very impressive stuff and very grateful that you’re doing what you’re doing.

DrSR: Thank you, Michael. It’s a pleasure to be with you. And I always enjoy our conversations. You’re great at insight and partialness. So that’s great.

DrMR: Thank you. And before I let you go, where can people track you down, follow your work, or connect with you if they wanted to hear more from you or to reach out?

DrSR: I think the best way to reach me is by email. My email is [email protected]. That is probably the best way to reach me. And I’ll be able to respond to them or get them in touch with whatever we can do to help them through my scheduling people, if they wish to come and see me. Or if you have some simple questions I can always advise them.

DrMR: Awesome. Well, Satish, thank you again so much. It was a great conversation.

DrSR: Thank you, Michael. And have a lovely evening.

DrMR: You too, take care.

DrSR: Take care.

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