Selecting Optimal First-Line Treatments for Patients With Opioid-Induced Constipation


William F. Peacock, MD; Conar Fitton, MD; and Neel Mehta, MD, discuss the multidisciplinary approaches to selecting therapies for patients with opioid-induced constipation.

William F. Peacock, MD: Everybody uses over-the-counter laxatives and stool softeners for all their patients. They work some of the time. What’s the data on that? How often do they work? What’s the real number?

Conar Fitton, MD: The hard part is there haven’t been any randomized control trials for that. When you look at what percentage of patients are satisfied, it’s low because the pathophysiology of OIC [opioid-induced constipation] is unique. The μ-opioid receptor is densely lined in the GI [gastrointestinal] tract, small bowel, and colon. I always love talking to the medical students and residents about this, because you can watch their heads explode back from when they were in their pathophysiology days. But when you talk about the submucosal and the myenteric plexus and how it binds the excitatory and inhibitory neurons, you’re decreasing propagation and increasing resting sphincter tone. You’re losing that secretion into the small bowel.

It isn’t 1 thing. It isn’t just that they’re going infrequently. It isn’t just that they feel that they have to use the restroom all day. It isn’t just that it’s harder and drier. It’s all of them. Once I explain to the patient, “This is why this isn’t working for you, and this is why if we can have competitive antagonism and we can block these receptors”—you have to say what we’re saying here for people to understand. I tell them, “Take this before you take your pain medicine in the morning,” because people don’t understand that. They take a handful of pills at once, and then they go along their way. But once I explain that to people, it hits home that it’s a multifactorial mechanism. It isn’t surprising that patients aren’t satisfied with the other ones. We have good treatments. We have to get to that point—hopefully earlier than later—where we intervene, lock the actual mechanism, and then patients can get rapid relief.

Neel Mehta, MD: Yes. The challenge is that there are too many permutations and combinations and a very middle to low compliance of these treatments. Any trial for these things is generally going to be difficult to interpret and probably have a low success rate. When you start to talk about satisfaction, patients get very frustrated because they don’t know what’s the best or how often to take it. It’s a real challenge. It’s an easy bar to meet, to find something that works better when you go to the underlying mechanism that Conar just talked about, this immune receptor activity.

The way I talk to patients about it is I say, “You have 1 issue. This pain medication is binding to this immune receptor in certain parts of your body to help you get pain relief, but in other parts of your body, that’s unfortunately where it causes adverse effects. If there were something that could affect only that portion, that would be ideally suited.” That’s where we talk about PAMORAs [peripherally acting μ-opioid receptor antagonists].

William F. Peacock, MD: How long would you wait before switching to a different therapeutic option? That isn’t a question for me because, by the time I see them, the patient isn’t waiting anymore. It sounds like Conar is in the same boat as I am, which leaves Neel.

Neel Mehta, MD: Yes. That’s a great question. My patients ask me that, and I vary it based on their symptoms. They aren’t quite bad enough to see you guys, but they’re miserable. If they’ve tried these things in some way, then I give them a few days to a week of the first-line therapy to get them onto a second-line therapy. If they’re talking about it for the first time and haven’t tried anything, or the conversation came about only because of a question that I asked, then I give them 2 to 3 weeks on the laxatives in that class of first-line therapy.

William F. Peacock, MD: That’s a long time.

Neel Mehta, MD: Yes. It’s the same as any symptom. We get people with back pain. The first time they’re experiencing back pain, we don’t give them an aggressive treatment right off the bat. Because if they’re tolerating it, there are conservative measures. A lot of it is also patient-shared decision-making. They look at it as, “I can take some milk of magnesia. That’s worked for me in the past.” If they start venturing a little too far, they say, “I’ll increase my leafy greens and do some prune juice.” I’ll remind them that hasn’t been shown to be effective in this type of constipation.

Conar Fitton, MD: That’s a very reasonable approach. You have to vary it on degree. I can’t tell you how many patients I see a year who are sent in because their significant other tells them that they aren’t normal, but their bowel habits are actually normal. If someone has 3 bowel movements a day and they’re formed and have no other symptoms, we consider that within the normal range. If someone has 3 to 4 bowel movements a week but that’s how they’ve been for 20 years and they have no symptoms otherwise, we consider that normal. But if those patients say, “Normally, I went twice a day. Now it’s been 3 days since I’ve gone,” and they haven’t tried anything, then 2 weeks is reasonable.

But as Neel was saying, it’s about having that shared decision-making and a plan with the patient to say, “This is what we’re going to try. We’re going to start a stool softener. On day 3, we can try an over-the-counter stimulant if that doesn’t work. See if that combination works.” It will work for some patients, but for some patients it won’t. It’s important to have that backup plan to say, “If this doesn’t work, you’re going to meet criteria for these second-line therapies, which are very efficacious for the patients who need it.” Those are the patients who are going to benefit significantly. That approach is perfect.

Neel Mehta, MD: Yes. We’ve probably all been there, or at least Conar and I, where we’ve given them second-line therapies and they weren’t quite mentally prepared for it. You give them the drug to be taken daily with refills and they come back after a month and don’t need any refills. The patient has to be invested in this too, especially when you’re starting the conversation. That’s part of what we think about in this shared decision process.

Transcript Edited for Clarity

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