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Many Options Available for Patients With Refractory IBS
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By the time a patient with irritable bowel syndrome gets to a tertiary referral physician like me, they have likely tried a lot of treatments.
Invariably, they will have tried over-the-counter treatments or even prescription medications before they get to me that just do not work well enough to give them adequate relief. In many instances, however, patients have not always tried these treatments for long enough or at the appropriate doses. There is still a chance they could find relief through these therapies, they just need to know how to use them in the right combination.
When we get a patient with refractory IBS, it is important to start by reviewing with them potential contributors that might be factoring into their disease. This includes things like diet, the amount of sleep they are getting, stress and how much they exercise. I try to emphasize that symptom relief can often be maximized by improving these so-called ‘life-style’ factors.
Once they show they have maximized those factors as much as possible, we move onto pharmacologic treatments. From there, we have to think about what their predominant symptom(s) is.
Neuromodulators
In patients with predominant pain, which is often the hardest symptom to control, we have to think about the best ways to control that pain. It is important to note that narcotics should not be used in patients with functional abdominal pain, such as IBS, as they have not been shown to be effective long-term in treating functional abdominal pain, and patients often need dose escalation. In some cases, the pain can actually get worse in the long run. So, narcotics are definitely not recommended in these patients.
One area we can turn to for functional abdominal pain are neuromodulators such as tricyclic antidepressants (TCA), SSRIs, SNRIs, gabapentin or pregabalin (Lyrica, Pfizer). Some patients get a little uneasy when you tell them you are going to prescribe an antidepressant medication. They think you are not being honest with them or trying to deceive them in some way. You have to explain that although they are approved for the treatment of depression or anxiety they work by reducing the firing of the nerve endings that control pain, and in the end, many patients will accept them. We also like to reassure them that in many instances we are starting these medications at lower doses than used for psychiatric purposes.
It is worth noting that abdominal pain is one of the most common complaints seen by gastroenterologists and is particularly common in functional bowel disorders including IBS, functional dyspepsia and functional abdominal pain. For this reason, it is essential for gastroenterologists to be familiar with the treatments for abdominal pain and be comfortable counselling their patients on them.
Non-Pharmacologic Therapies
In the realm of abdominal pain, we can also turn to non-pharmacologic therapies. These are important adjuncts that GIs also need to be familiar with.
We regularly work with psychologists who can provide treatments like cognitive behavioral therapy and gut-directed hypnosis. Not every GI may be lucky enough to work alongside a GI psychologist, but it’s something they should feel comfortable referring patients out to.
Diet continues to be a big factor in IBS treatment. I always emphasize it for patients because it really can make a significant difference. Of course, we have low-FODMAP, but sometimes, we even go for the gluten-free diet. A recent study published in Gastroenterology looked into specific food allergies using confocal light microscopy and their role in the pathogenesis of IBS. Further studies are needed in this area, but this technique could give us a way to target dietary interventions.
I also think it is important that we do not overlook other complementary and alternative treatment. Although the placebo-controlled data are not the strongest, we still refer patients to acupuncture. Even over-the-counter peppermint oil has shown to improve IBS symptoms.
IBS-C
In patients with constipation there are a number of FDA-approved drugs like Amitiza (lubiprostone, Takeda), Linzess (linaclotide, Allergan), Trulance (plecanatide, Syngery), and more recently tenapanor (Ardelyx). Over the counter laxatives such as polyethylene gycol and milk of magnesia may improve constipation but are not likely to have significant effects on abdominal pain.
Probiotics also offer us another option to try. When used in patients with IBS-C, they may improve bowel function and bloating. There are a lot of options on the market, so patients generally request some guidance on which ones they should try. Generally, we suggest patients try Bifidobacterium species, Lactobacillus plantarum, or a combination of probiotics.
IBS-D
I generally start patients with diarrhea predominant symptoms on a general antidiarrheal medication like Imodium (loperamide, Johnson & Johnson) or Bismuth (Pepto-bismol). Patients with frequent diarrhea should take it every day. The dose should be started low (eg, 2-4 mg per day) and then increased as needed, however no higher than 16 mg per day. Most patients do not need more than two to four tablets per day. The dose should be titrated to achieve a better stool consistency, though constipation should be avoided. Unfortunately, abdominal symptom is rarely improved.
There are currently three FDA approved drugs for IBS-D, rifaximin, alosetron and eluxadoline. Xifaxan (rifaximin, Salix) is a minimally absorbed antibiotic that has been shown to improve IBS symptoms including abdominal pain, bloating and diarrhea. The dose is 550 mg three times a day for 14 days. Patients whose symptoms improve and have recurrence may benefit from an additional course of rifaximin. The drug is generally well tolerated.
Viberzi (eluxadoline, Allergan) is a mu- and kappa-opioid agonist and a delta-opioid antagonist, so it has a nice combination of targets. In animal models that mix is able to improve stool consistency while reducing abdominal pain. Eluxadoline has been shown to improve the IBS symptoms, particularly stool consistency. Eluxadoline has been associated with pancreatitis and sphincter of oddi dysfunction in patients without a gallbladder or patients who have at least three alcoholic drinks per day. Therefore, the drug is contraindicated in these patients.
Alosetron is a HT3 antagonist. It was initially FDA approved at a dose of 1 mg twice daily. Although the medication is effective in treating women with IBS-D, due to the side effect of constipation the recommended dose is now 0.5 mg once a day. It can be increased to 1 mg twice daily provided there is no constipation and the patient continues to have inadequate of symptoms. Another side effect of alosetron is ischemic colitis, which occurs in approximately 1:750 patients. This side effect is not dose dependent.
There are other therapies that show promise, like bile acid sequestrants (eg, cholestyramine or colestipol) however placebo-controlled trials are lacking at this time. Nevertheless, particularly in patients in whom diarrhea is the predominant symptoms we frequently recommended a trial with them.
- Reference:
- Choung RK, et al. Gastroenterology. 2019;doi:10.1053/j.gastro.2019.05.042
- For more information:
- Anthony J. Lembo, MD, is director of Motility Services at Beth Israel Deaconess Medical Center and an associate professor of medicine at Harvard Medical School. He can be reached at alembo@bidmc.harvard.edu.
Disclosure: Lembo reports serving as a consultant for Alkermes, Arena, Ironwood, Orophomed, QOL Medical, Ritter, Shire, Takeda and Vibrant.