Fariborz Rezai, MD, FCCP FCCM, Rutgers New Jersey Medical School 

What I see as the major unmet need in the management of opioid-induced constipation [OIC] is the general unawareness that opioid-induced constipation is common and can be prevented and treated effectively using medications we have. The most common unmet need that I see is that health care professionals, physicians, nurse practitioners, and PAs [physician assistants], either don’t have the time or don’t have the knowledge base to effectively discuss opioid-induced constipation with their patients who are being prescribed opioids. I find that I spend a lot of my time educating my peer group, other health care professionals, nurse practitioners, PAs, physicians, and DOs [doctors of osteopathic medicine]. I find myself educating this group of people to better understand that when they are prescribing an opioid to treat chronic pain and sometimes even acute pain, that the patient frequently may develop opioid-induced constipation and that we have medications that effectively address and treat opioid-induced constipation. Specifically, the peripherally acting µ-opioid receptor antagonists that are designed to treat opioid-induced constipation and when taken on a daily basis, can indeed prevent the development of opioid-induced constipation. I find these medications to be highly effective. So the greatest unmet need I see is a lack of education, which also falls into a lack of time from the busy primary care practitioners and other busy health care professionals to have an in-depth discussion with the patient addressing the issue of opioid-induced constipation.

As time goes on, the general acceptance of the usage of the peripherally acting µ-opioid receptor antagonists does appear to be increasing, both by the pain management community but also by other health care professionals who are prescribing opioids to treat chronic pain. In other words, as time has gone on for the last decade or so, I have seen an increase in the educational background, in the knowledge base, of health care professionals in both understanding the concept of opioid-induced constipation and understanding that there are effective treatments for opioid-induced constipation available. I have seen an uptake— especially for patients in my hospital, but also for outpatients—in recommendations from primary care practitioners for the patient to utilize lifestyle changes: good hydration, good levels of physical activity, eating fruits and vegetables, and making sure that the patients are utilizing the over-the-counter medications when needed. Part of this is also recognizing that all of those efforts may not be successful in helping the patient maintain their baseline level of bowel function, and frequently we may need to address and treat this using a peripherally acting µ-opioid receptor antagonist.

The take-home message, I believe, is that opioid-induced constipation can be a very difficult problem for patients, but also for health care professionals to discuss with the patient. I think we should all become comfortable discussing the adverse effects of any medications we are prescribing, and also the potential adverse effects, so the patients can both address and perhaps prevent the development of opioid-induced constipation. We laugh about it because, let’s face it, we’re talking about bowel function, and many of us find this somewhat amusing. But from the patient’s point of view, I’ve had patients in which the opioid-induced constipation is dramatically affecting their life. It’s impacting their ability to interact with their family, to interact at work, and for them to even leave the house. I’ve had patients tell me that the opioid-induced constipation is so bad that they’re afraid to leave their house because they are concerned that they may have to have a bowel movement and they won’t be prepared for that. Whereas if a patient is having their opioid-induced constipation effectively treated, they can just take their medication, have their bowel movement, go on with their daily activities, and maintain a lifestyle and increased activity. In many cases, the opioids provide these patients with the opportunity to have better pain control and therefore increased functional activity. The whole goal of opioids is comfort, as well as maintenance, and increasing patients’ ability to do the things that they want to do to increase their functionality. If we can control, address, and treat opioid-induced constipation, it is 1 additional step that helps our patients maintain their healthy lifestyles.

I think there are quite a few unmet needs in the management of OIC. One is education. I think even in the health care world, it’s underdiagnosed or it’s diagnosed but undertreated, for a wide variety of reasons. To what I mentioned earlier, OIC or constipation in general, is something patients don’t like bringing up and physicians don’t like spending a lot of time talking about because of the nature of the diagnosis. But I think it’s something that’s worthwhile to focus on. A lot of times, I know primary care physicians will send the patients to a GI [gastrointestinal] physician, but this is something that a primary care physician can absolutely handle to the best of their ability. Obviously, if there are other, more complicated reasons they should be referred to GI. But my point is that I think more educational awareness of OIC would be beneficial for treating these patients. Other treatments that come down the pipeline may be a good option or an additional option to what we have now. That’s to be seen, but again, I think the focus is education. Once we have more education, there will be more awareness, and then there will be a better treatment.

I’m a physician and clinician who likes to be very thorough with my patients. It’s probably because I’m more of a critical care physician, where I review systems or system-by-system management. My take-home message is: focus on every diagnosis your patient has at every visit. Don’t just assume that there’s no change, because some of the slightest changes can really make a difference for your patient with long-term morbidity and even mortality. So keep that in mind.

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Gerald Sacks, MD, and Fariborz Rezai, MD, FCCP FCCM, discuss unmet needs and the future treatment landscape in managing opioid-induced constipation. 

Unmet Needs in OIC Management 

The question is: OIC [opioid-induced constipation] is a common diagnosis and it’s often undertreated, and why is that? I think most people realize that opioids cause constipation. I think that’s a no-brainer. The public knows that; clinicians know that. But I think the misunderstanding is that it’s not treatable. That’s key: focus on the diagnosis. The patient has OIC. For whatever reason, they’re on opioids as part of their disease process that’s being treated by a health care practitioner. The issue here is the OIC they’re suffering from. It’s important to go over the review systems, but really focus on the treatment plan: lifestyle modification, diet, staying active, and also what type of bowel regimens they’re on. Is something like methylnaltrexone beneficial to them? Would that work? If we’ve tried other approaches and they haven’t worked, then it’s key to start something like methylnaltrexone to inhibit the opioid effect on the gut. Again, when do you start this? Well, it’s probably appropriate to have those discussions from day 1 because even if the patient is not suffering from constipation at that point, they may suffer from it at some point, and that’s key. It’s better to be proactive than having a patient who’s been constipated, or having OIC, possibly for a couple of years. Then it’s more difficult.

I have advice for providers who treat patients with OIC. Obviously, you are seeing the patient for multiple reasons, but if you’re treating them for OIC, if it’s part of the differential, if it’s part of their diagnosis, I think you have to spend a fair amount of time to really judge: how is their OIC? Is it improving? Is it not improving? Do a good examination, get a good history. How often are their bowel movements? What type of bowel movements? What is the stool consistency? I think those are all important to determine where your patient stands. Because obviously, the treatment they get will depend on if they’re getting better, or worse, or stagnant. Again, just because you treat OIC once doesn’t mean it’s gone. That diagnosis is like any other diagnosis, such as AFib [atrial fibrillation] or hypertension. That diagnosis stays with the patient, at least for the foreseeable future. I think a good clinician will evaluate that diagnosis at every visit and determine what is the appropriate treatment at that time.

Fariborz Rezai, MD, FCCP FCCM, comments on the importance of being proactive in addressing opioid-induced constipation early on with patients and shares advice for providers. 

Addressing Opioid-Induced Constipation With Patients 

 Many practitioners are reluctant to discuss opioid-induced constipation with their patients because of their own personal uncomfortableness in discussing the topic. I have no problem discussing all GI [gastrointestinal]–related activities, and GI doctors have no issue or problem discussing this part of the body and normal gastrointestinal functions. But I do find that frequently many patients, as well as many health care professionals, are reluctant to address and treat opioid-induced constipation. Primarily this is because of a general uncomfortableness in thinking about and discussing normal bowel function. Indeed, when I ask patients who are taking 6 or 8 opioid pills per day, whom have been suffering with opioid-induced constipation for months or years, about whether their health care professional has ever brought up the subject of opioid-induced constipation and discussed the treatment of opioid-induced constipation, frequently the answer is no. It’s never been brought up or discussed. In other words, our primary care practitioners are so busy addressing diabetes, hypertension, chronic pain, and all issues associated with the opioids, that frequently they may not have the time to discuss the treatment of opioid-induced constipation.

As a pain management practitioner, I feel it’s my obligation to discuss and treat any adverse effects that may be caused by medications that I’m prescribing. So I look at the medications that I’m prescribing and then consider the potential adverse effects of those medications. Therefore, I need to have a discussion with every patient who is on opioids about their bowel function. That includes discussion about how frequently they’re going to the bathroom, whether they’re having success in the bathroom, whether they feel they’re straining, whether they feel it’s very uncomfortable, how often they go to the bathroom, and the quality and quantity of their stool. What we try to do is have the patient return to their baseline level of bowel function by utilizing medications and lifestyle enhancements so that they’re able to maintain their baseline level of bowel function to maintain their level of activity.

Most of the patients coming into my office are actually already taking opioids. Indeed, 100% of my patients are referred by other physicians, so those patients are frequently sent to me for management and treatment of their chronic pain. Part of that is management and treatment of their opioid usage. It’s rare that I have a patient come in, referred by a primary care practitioner or an orthopedic surgeon or a spine surgeon, who has had the topic of opioid-induced constipation discussed with them in any detail. Some of my primary care colleagues are comfortable and familiar with treating opioid-induced constipation with over the counter medications and, sometimes, with peripherally acting µ-opioid receptor antagonists. However, it’s not common for orthopedic surgeons, spine surgeons, and other referring sources—podiatrists, neurologists, etc—to send a patient to me who is taking opioids and is also concomitantly taking a peripherally acting µ-opioid receptor antagonist. It’s up to me to educate the patient and sometimes also to educate the practitioner—whether it’s an orthopedic surgeon, a spine surgeon, a neurologist, an endocrinologist, a primary care practitioner—in the appropriate treatment of opioid-induced constipation using over-the-counter medications, lifestyle changes, increased hydration, increased intake of fruit and vegetables, and also the appropriate usage of peripherally acting µ-opioid receptor antagonists.

In my practice, I try to make the discussion about opioid-induced constipation a normal part of each patient’s visit. When a patient comes in and I’m discussing their chronic pain, we ask about the quality of the pain, the intensity of the pain, how often it occurs, and what they’re doing to decrease their pain, whether it’s pharmacologically, using physical therapy modalities, or lifestyle changes. Part of that discussion is on any adverse effects, either potential or actual, that are occurring from the medications being prescribed. Part of that discussion sometimes is an in-depth analysis of the adverse effects that the patients are having from their opioids. The most common adverse effect that my patients on opioids have is opioid-induced constipation. This can be addressed and treated effectively using peripherally acting µ-opioid receptor antagonists.

 Constipation is something that, depending on the patient, some patients love talking about. But you’re right: The majority of patients are a little private about their bowel movements. They don’t want to talk about constipation. As a good health care practitioner, our job is to really look at the system-based system. When you’re at the GI, you’re asking those questions for your patient. But you don’t want to just say, “How are your bowel movements?” That’s not the right way to ask the question. Say, “How often do you have a bowel movement? What’s the consistency?” Try to narrow down all the little nuances with that. Try to understand: Does a patient have constipation? Do they not? What’s the etiology? Because if you ask the patient, “Are you constipated?” they may say no. In their mind, they’ve had 1 bowel movement a week, and they feel that’s normal. It’s important to decipher how often and what type of bowel movements they’re having because you, as the clinician, have to make that decision. Are they constipated? Are they not? What type of constipation? It’s very important how you phrase that question. Make the patient comfortable. You’re the physician. You’re the clinician. You’re treating the patient. It’s part of the review system. It’s part of the physical examination. You really need to ask the question in a thoughtful manner so you can get the appropriate answer from your patient.

Gerald Sacks, MD, and Fariborz Rezai, MD, FCCP, FCCM, share their personal experience in approaching and openly communicating the management of opioid-induced constipation with patients.

Patient Provider Communication for Managing OIC 

 It’s probably more important for patients on the outpatient side, but we do physical activity in the ICU [intensive care unit] setting as best as we can. We do early mobility, even on patients on the ventilator. The physical therapist, the nurse, and other health care practitioners will walk the patient around the unit. Physical activity is really key to the overall health of the body but also for having a regular bowel movement. Obviously, diet plays an important part. The appropriate balanced nutrition with appropriate vegetables, fruit, and dietary fiber helps prevent OIC [opioid-induced constipation] and other types of constipation. It doesn’t hurt for everybody—as best as they can—to be as active as they are permitted to be. Obviously, you must speak with your primary care physician regarding what you can and can’t do. It’s important to be physically active on a daily basis even if you’re not suffering from any constipation. It maintains the whole body’s homeostasis, including the bowel movements and regular bowel movements. That all comes into play. Appropriate sleep, eating a healthy balanced diet, and exercising on a regular basis all play a part in the lifestyle modification that patients should adhere to if they want to prevent any type of constipation, including OIC.

 There are numerous other products. Over-the-counter medications are used to address and treat opioid-induced constipation. Whenever I have a patient taking opioids, 1 of the first things we discuss is the prevention and treatment of opioid-induced constipation. The goal is to prevent an episode of opioid-induced constipation. The last thing I want for a patient is to have to go to the emergency department for a manual disimpaction. I still remember manually disimpacting patients when I was a young physician. It’s an extremely unpleasant experience for the patient as well as the health care professional, so we try to avoid that. Certainly we try to avoid visits to the emergency department to treat constipation as well. When a patient is prescribed opioids, I initiate the discussion with the patient in terms of how to prevent the adverse effects from the opioids. I frequently will have the patient obtain a stool softener or perhaps a stool-softener-and laxative combination. Both medications are available over the counter. I frequently will have the patient utilize MiraLax, which is available over the counter. It used to be a prescription item but is now available over the counter for the prevention and treatment of opioid-induced constipation. Certainly, we have patients maintain their active and healthy lifestyle in terms of maintaining their hydration, drinking enough fluid, walking around, doing physical therapy, maintaining their physical activity level at a high level, and utilizing the opioids to treat the pain. Management of pain ensures they can do more activities, be more active, do physical therapy, and take a walk on a daily basis if that’s what they’re able to do. These over the counter medications can be helpful, but frequently patients will still—even when they’re taking a stool softener, a laxative, a suppository, or even another laxative—have opioid-induced constipation. That’s where I prescribe the peripherally acting µ-opioid receptor antagonists.

 Lubiprostone and linaclotide [Linzess] are used in constipation, especially for patients with irritable bowel syndrome. They’re a little less specific because they call stimulation of fluoride release or they work with the chloride channels, depending on which drug we’re talking about. But overall, they do the same thing, which is trying to increase luminol fluid. By increasing that luminol fluid, it allows the feces, the contents, to be moister to support its passage through the gut. It’s not something we really use for OIC. For OIC, we’re using something that blocks µ receptor as more of a strategic and pinpoint treatment really taking care of the ideology. This is a little more generic, where this causes more fluid in the gut. Not to mention that this also causes a lot of bloating and discomfort for the patients, so it’s not something that I use at all.

The role of lifestyle modifications and over-the-counter products to prevent opioid-induced constipation in patients is discussed. 

Fariborz Rezai, MD, FCCP FCCM, Rutgers New Jersey Medical School

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