Irritable bowel syndrome (IBS) is a chronic, relapsing functional gastrointestinal (GI) disorder.1-3 Patients who develop IBS report abdominal pain and altered bowel habits (Table 1)1,4-6 with no identifiable cause. Patients may report a predominance of diarrhea (IBS-D) or constipation (IBS-C), but both may occur in an individual patient. Some patients report only abdominal pain and bloating (IBS-PB).1 IBS prevalence (all types) is estimated at 10% to 20% of the US population and at any time, up to 2% of the population experiences active symptoms.2,3 Women are up to 3 times more likely to develop IBS than men in the United States, and those with the condition are at increased risk of ectopic pregnancy and miscarriage.4,5 Many adult patients report that they have experienced symptoms since childhood. Onset before 35 years of age is common.7
The etiology of IBS has not yet been identified. Examination of the large and small bowels has revealed altered GI motility. This delays meal transit in patients who report constipation but accelerates transport in patients who report diarrhea. Patients with IBS also have visceral hyperalgesia. Microscopically, some bacterial overgrowth and microscopic inflammation has been identified in patients who have IBS.8
In addition, IBS is associated with psychopathology. Patients with IBS tend to have a higher incidence of anxiety disorder, catastrophizing, major depression, panic disorder, and somatoform disorders than the general population.1,9 A major concern in patients with IBS is suicidal attempts or ideation.10 Clinicians should heighten awareness around this risk.
Patients need to know 2 things: Symptoms tend to be chronic and exacerbate from time to time, and individuals need to avoid stressors and triggers.4 Patients with IBS need 3 types of support.
First, they need support to address the common psychological comorbidities. Cognitive behavioral therapy and judicious use of antidepressants may reduce symptoms or strengthen coping skills.3,6,10
Second, they need advice about dietary measures that can ameliorate or prevent symptoms. Fiber supplementation can improve constipation and diarrhea, but it may cause bloating or distention. Clinicians should note that a Cochrane systematic review of bulking agents and fiber in IBS found that these medications had no benefit.11 Regardless, many patients report improvement.
Third, additional dietary recommendations include staying adequately hydrated, limiting fermentable oligo-, di-, and monosaccharides and polyols, and supplementing calcium for patients who avoid lactose entirely.12,13
Pharmacologic treatment is considered adjunct to lifestyle management and must be symptom directed.6 Clinicians can choose among anticholinergics, antidiarrheals, bulk-forming laxatives, chloride channel activators, guanylate cyclase C agonists, prokinetics, serotonin receptor antagonists, and tricyclic antidepressants. The choice of the drug(s) used depends on the patient’s symptoms, preference, and previous responses.6 The Figure shows the typical approach to treatment; note that the stepwise approach is deceptively simple, and no comparative effectiveness studies support its structure.6 For many patients, it will take time and trial and error to find the most successful strategy.14
In the past several years, the FDA has approved many agents to treat IBS. Table 2 describes the newer agents.15-20
With recent developments, the likelihood of successful treatment for patients with any type of IBS is greater than ever before. Pharmacists need to take note of specific indications, the most common adverse reactions, and potential drug interactions. Given time and trial of multiple interventions, most patients will learn to live successfully with IBS and control its exacerbations.
Jeannette Y. Wick, RPh, MBA, FASCP, is assistant director of the Office of Pharmacy Professional Development at the University of Connecticut School of Pharmacy in Storrs.
- Treatment for Irritable Bowel Syndrome
- How do doctors treat IBS?
- IBS-C: New Treatments Deliver Promising Management
- Medications currently or newly approved for IBS-C
- Medications on the horizon for IBS-C
- What now?
- IBS Medications and Supplements
- Types of IBS
- Medications for IBS-D
- Side Effects for IBS-D Medications
- Medications for IBS-C
- Medications for Abdominal Pain and Bloating
- Medication for Irritable Bowel Syndrome in Adults
Treatment for Irritable Bowel Syndrome
How do doctors treat IBS?
Doctors may treat irritable bowel syndrome (IBS) by recommending changes in what you eat and other lifestyle changes, medicines, probiotics, and mental health therapies. You may have to try a few treatments to see what works best for you. Your doctor can help you find the right treatment plan.
Changes to what you eat and other lifestyle changes
Changes in what you eat may help treat your symptoms. Your doctor may recommend trying one of the following changes:
- eat more fiber
- avoid gluten
- follow a special eating plan called the low FODMAP diet
Read more about eating, diet, and nutrition for IBS.
Research suggests that other lifestyle changes may help IBS symptoms, including
- increasing your physical activity
- reducing stressful life situations as much as possible
- getting enough sleep
Your doctor may recommend medicine to relieve your IBS symptoms.
To treat IBS with diarrhea, your doctor may recommend
- rifaximin (Xifaxan), an antibiotic
- eluxadoline (Viberzi)
- alosetron (Lotronex), which is prescribed only to women and is prescribed with special warnings and precautions
To treat IBS with constipation, your doctor may recommend
- fiber supplements, when increasing fiber in your diet doesn’t help
- lubiprostone (Amitiza)
- linaclotide (Linzess)
- plecanatide (Trulance)
Other medicines may help treat pain in your abdomen, including
- antidepressants, such as low doses of tricyclic antidepressants and selective serotonin reuptake inhibitors
- coated peppermint oil capsules
Follow your doctor’s instructions when you use medicine to treat IBS. Talk with your doctor about possible side effects and what to do if you have them.
Your doctor may recommend medicine to relieve your IBS symptoms.
Your doctor may also recommend probiotics. Probiotics are live microorganisms, most often bacteria, that are similar to microorganisms you normally have in your digestive tract. Researchers are still studying the use of probiotics to treat IBS.
To be safe, talk with your doctor before using probiotics or any other complementary or alternative medicines or practices. If your doctor recommends probiotics, talk with him or her about how much probiotics you should take and for how long.
Mental health therapies
Your doctor may recommend mental health therapies to help improve your IBS symptoms. Therapies used to treat IBS include
- cognitive behavioral therapy, which focuses on helping you change thought and behavior patterns to improve IBS symptoms
- gut-directed hypnotherapy, in which a therapist uses hypnosis—a trance-like state in which you are relaxed or focused—to help improve your IBS symptoms
- relaxation training, which can help you relax your muscles or reduce stress
IBS-C: New Treatments Deliver Promising Management
Currently, treatment for irritable bowel syndrome with constipation (IBS-C) focuses on treating symptoms, preventing flares, and avoiding triggers. Lifestyle adjustments are common. These changes include eating more fiber, drinking more water, exercising regularly, and eliminating problematic foods. Very few medications for IBS-C exist.
Treatment for IBS-C is not one-size-fits-all. What works for you may not work for another person. However, advances in treatments are good for everyone. Each year, researchers and doctors investigate potential treatments for people living with this common digestive disorder. Many of these hold promise for the future.
Medications currently or newly approved for IBS-C
The U.S. Food and Drug Administration (FDA) has approved two medications for the treatment of IBS-C:
In 2008, the FDA approved lubiprostone (Amitiza) for the treatment of IBS-C. At the time, it was the only FDA-approved medication for IBS-C. Lubiprostone increases the fluid your small intestine secretes. The extra fluid helps pass stool more easily, which reduces your risk for constipation.
Lubiprostone is only available for use in women ages 18 and older. Men and children with IBS-C shouldn’t use it. Side effects include nausea, abdominal pain, and diarrhea.
In 2012, the FDA approved linaclotide (Linzess) for the treatment of IBS-C. This medicine is also approved for the treatment of chronic idiopathic constipation (CIC). This type of constipation occurs regularly and doesn’t respond to typical treatments.
Linaclotide helps ease the symptoms of IBS-C by spurring more frequent bowel movements. It can also ease abdominal pain. The most common side effect of this medicine is diarrhea.
Medications on the horizon for IBS-C
Researchers and pharmaceutical companies are investigating and developing newer treatments for people living with IBS-C. Of course, the ultimate goal is a cure. But until that time, new developments hold great promise. Some of these developments involve medications, and some are more lifestyle focused. Here is what you might expect to see in the future:
In 2017, the FDA approved plecanatide (Trulance) for the treatment of CIC. Currently, it’s not prescribed to individuals with IBS-C. However, the medication holds promise for these people, and the manufacturer says it’s being evaluated for that purpose.
Like lubiprostone, plecanatide works in the upper gastrointestinal (GI) tract to stimulate fluid produced by the intestines. The extra fluid makes passing bowel movements easier. The extra fluid can also help maintain regular GI function.
Bile acid modulators
A class of drugs called bile acid modulators has been used to treat constipation. Bile is a fluid produced by your liver. After a meal, your liver sends more bile into your stomach and intestines via the gall bladder. Researchers discovered that this medication might move food and waste through your GI more quickly. This type of medicine could alter the level of bile in your GI tract, and that could help stimulate your bowels if you’re constipated.
Your intestines are filled with billions of bacteria and microorganisms. The balance of “good” bacteria may play a role in your overall health. Probiotics are good bacteria. Research suggests having a healthy balance of probiotics in your gut may ease symptoms of IBS, including pain and gas.
Building up and maintaining healthy bacteria in your body may help improve IBS-C symptoms. You can increase your supply of probiotics by eating foods that are filled with this good bacteria or taking supplements.
Currently, existing studies are limited, but the future holds great promise for understanding the relationship between your bacteria and your gut health.
Targeted bacterial treatments
Eating more probiotics is healthy for many reasons, but a targeted bacterial approach may be more successful. Research suggests a cocktail of highly specific bacteria may help disrupt any bacterial imbalance in your GI tract and reduce or eliminate symptoms.
Healthy bacteria may play another role in treating IBS-C. This time the treatment involves what comes out of your body, rather than what goes in. Studies are limited, but research suggests a fecal transplant may transfer healthy bacteria from one person’s GI tract to another. The goal is to help good bacteria colonize in the bowels so that symptoms of gastrointestinal disease will be reduced or eliminated.
Talk with your doctor about these and other treatments that might hold promise for you. Some of these are years from being available, but others could be right around the corner.
Make sure you keep regular appointments with your doctor so you can stay on top of new ideas, new medications, and new treatment options. Let your doctor know you would like to consider something different if you could be a good candidate for it.
IBS Medications and Supplements
By Dr Ahmed Zayed MD, MCh
Irritable bowel syndrome (IBS) is a common disorder indicated by a number of uncomfortable symptoms that affect a patient’s quality of life. Treatment of this disorder revolves around management of symptoms. A wide array of medications and supplements are used for the management of IBS, and this article will help you learn more about them and their safety and efficacy.
Types of IBS
Before we start discussing medications and supplements for IBS, it’s important to learn one thing – not all cases of IBS are the same. In fact, we can classify IBS into different categoriessuch as:
- IBS with constipation (IBS-C) – indicated by stomach pain and discomfort, lumpy or hard stool, bloating, and abnormally delayed or infrequent bowel movement
- IBS with diarrhea (IBS-D) – characterized by symptoms such as discomfort and pain as well as a loose or watery stool, urgent need to empty your bowel, frequent bowel movements
- IBS with alternating constipation and diarrhea (IBS-A) – as you can presume, this type of IBS is indicated by periods of constipation-like symptoms followed by periods of diarrhea
Each type of IBS has about an equal number of patients. Bear in mind that sometimes a patient can have one IBS type and then experience some other type over time, i.e., it’s possible to alternate between types.
Medications for IBS-D
Stress, imbalance of gut microbiota, certain foods, and many other factors can contribute to IBS-D. In many cases the underlying cause of this problem is unknown, but there’s a lot we can do to manage it. A better understanding of the mechanisms associated with IBS-D would help ensure further development of new drugs for successful management of this condition. Below, you can see the list of medications that are used to treat IBS-D:
- Rifaximin (xifaxan) – an antibiotic formulated to fight bacterial infection only in the intestines. Rifaximin is not like other antibiotics due to the fact it passes through the stomach into the intestines without reaching the bloodstream. That is why this antibiotic doesn’t treat infections in other parts of the body. A growing body of evidence confirms that taking rifaximin for two weeks improves several symptoms of IBS-D such as loose or watery stools, bloating, abdominal pain, and others
- Loperamide (Imodium/gastro-stop) – a synthetic anti-diarrheal medication that is primarily used to decrease the frequency of diarrhea. Besides IBS-D, this drug is also used to address gastroenteritis and short bowel syndrome. Loperamide works by slowing down the rhythm of digestion in order to give more time for the small intestines to absorb nutrients and fluid from food. A study which compared the efficacy of loperamide versus placebo for treatment of IBS-D found that subjects who took this medication experienced improvement in stool consistency, urgency, pain, and their overall subjective response was better compared to the placebo group
- Atropine (Lomotil) – an anti-diarrheal drug available in tablet and liquid form. It functions to slow down colonic motility to improve absorption of more liquid from the stool. As a result, the stool becomes firmer which alleviates diarrhea symptoms. The drug is designed for short-term use only
- Eluxadoline (viberzi) – a prescription medication formulated to address problems associated with IBS-D such as diarrhea and abdominal pain. The drug works directly in the intestines in order to slow down the movement of food during digestion. In addition, Viberzi reduces sensitivity to stimulation from nerves. One study found that Eluxadoline reduced symptoms of IBS-D in both men and women with sustained efficacy for more than six months
- Alosetron (Lotronex) – belongs to the class of drugs called 5-HT3 receptor antagonists which are used for management of severe IBS-D. Similarly to other drugs for this disorder, Alosetron works by slowing bowel movements through the intestines. A growing body of evidence confirms that Alosetron is effective for management of symptoms associated with IBS-D in men and women
- Bismuth subsalicylate (Kaopectate, Pepto-Bismol) – a medication that treats loose stools and diarrhea. Mechanism of action is similar to the drugs mentioned above, it works by slowing down bowel movements, but it doesn’t relieve other symptoms of IBS-D
- Calcium (supplement) – your body needs calcium to function properly, and while most of your calcium serves to strengthen teeth and bones, a certain portion participates in various bodily functions. These bodily functions include fluid secretion, muscle movement, nerve cell communication, and blood pressure. Due to these roles, calcium supplementation can be considered a viable management option for IBS-D
- Antidepressants – bearing in mind that antidepressants work at the level of the spinal cord and brain they block pain messages between the brain and GI tract. This leads to an improved brain-gut relationship which then aids the management of symptoms associated with this condition. Different types of antidepressants are available, such as:
- Tricyclic – amitriptyline (Elavil), Nortriptyline, imipramine – work to increase levels of norepinephrine and serotonin, two neurotransmitters as well as to block the action of other neurotransmitters in order to balance the concentration of these messengers in the brain for depression relief. Evidence shows this type of antidepressant can be effective in the management of diarrhea-predominant IBS
- SSRIs – citalopram, fluoxetine (Prozac), Paroxetine (Paxil), Sertraline (Zoloft) – selective serotonin reuptake inhibitors (SSRIs) reduce symptoms of moderate to severe depression and they work by increasing levels of serotonin in the body. These antidepressants are considered effective for treatment of IBS although the exact mechanism of action needs further research
- SNRI – duloxetine (Cymbalta), desvenlafaxine (Pristiq, Khedezla), levomilnacipran (Fetzima), venlafaxine (Effexor XR) – serotonin-norepinephrine reuptake inhibitors (SNRIs) treat depression as well as anxiety and other problems. They work by acting on chemical messengers or neurotransmitters to improve communication between brain cells. This is important if we bear in mind-brain function and gut health are connected with one another
Side Effects for IBS-D Medications
Every medication comes with a certain risk of side effects, but while some drugs have severe adverse reactions, others do not. Before you start taking some of the above-mentioned anti-diarrheal drugs, it’s important to learn more about their side effects and potential interactions with other medications. Some anti-diarrheal medications can cause problems with other drugs, such as:
- Antibiotics – in some cases antibiotics can cause a severe intestinal condition (Clostridium difficile-associated diarrhea), and it occurs weeks after antibiotic treatment has stopped. Anti-diarrheal medications can make this condition worse which is why it is usually not recommended to take these drugs after recent antibiotic use
- Prescription pain medicines – anti-diarrheal drugs decrease bowel movements so when used in combination with other anti-motility drugs they can cause constipation. Prescription pain medications including opioids belong to this category
- Blood-thinning medicines – it is recommended that patients with blood circulation and blood clot problems consult their doctor before using anti-diarrheal medications
- Gout medication – anti-diarrheal medications may affect uric acid levels and, thus, interact with gout drugs
- Arthritis medication – anti-diarrheal drugs may interact with absorption of medications taken for arthritis
- Diabetes medication – some anti-diarrheal medications may interact with anti-diabetes drug Tolbutamide
- Antiviral medicines for HIV – loperamide decreases absorption of antiviral drugs such as Saquinavir (Invirase, Fortovase)
Medications for IBS-C
Management of irritable bowel syndrome with constipation requires a well-crafted strategy that involves lifestyle modifications and medications. Using one approach doesn’t work, most patients find relief when they combine multiple approaches. Medications used for IBS-C include:
- Lubiprostone (amitiza) – belongs to the class of drugs known as chloride channel activators and it works by increasing the amount of fluid in the intestines to make the passage of stool easier. The medication is used for IBS-C as well as for chronic idiopathic constipation, and opioid-induced constipation. Studies show that the drug is both effective and well-tolerated for the relief of constipation and other symptoms linked with IBS-C
- Linaclotide (linzess) – works by enhancing secretion of chloride and water in the intestines to stimulate bowel movements and soften stools. It is used for IBS-C and chronic constipation with no known cause. Evidence confirm Linaclotide is an effective and well-tolerated treatment option for adults with IBS-C and it also works to alleviate other symptoms such as abdominal pain and discomfort
- Ispaghula husk (fybogel, ispagel) – a bulk-forming laxative used for constipation. Through its ability to increase the bulk of stool, the drug encourages bowels to move the stool through the digestive tract. This alleviates constipation and discomfort caused by it
- Psyllium husk (equate, konsyl, Metamucil, reguloid, fiberall, perdiem) – a form of fiber made from the husks of the Plantago ovata seeds. It soaks up water in the gut to make bowel movements easier
- Laxatives – substances that loosen stools and increase bowel movements. They are used to address constipation. We can divide them into the following categories:
- Stimulant laxatives (Bisacodyl – Correctol, Dulcolax, Sennosides – ex-lax, Senokot), castor oil, the plant cascara) – work by stimulating digestive tract walls to speed up bowel movements. They have a more rapid mechanism of action compared to osmotic laxatives
- Osmotic laxatives (Lactulose) – work by softening the stool to make it easier to move through the bowel
- Antidepressants – the same way these drugs help management of diarrhea, they can also improve symptoms linked with IBS-C.
- Tricyclic – amitriptyline (Elavil), Nortriptyline, doxepin, desipramine – when used in lower doses, they can help patients with IBS-C although they demonstrate greater efficacy when taken for IBS-D
- SSRIs – fluoxetine (Prozac), Paroxetine (Paxil), Sertraline (Zoloft) – evidence confirms SSRIs such as fluoxetine is a well-tolerated short-term treatment for pain and constipation-predominant IBS
Medications for Abdominal Pain and Bloating
A vast majority of patients with IBS experience abdominal pain, discomfort, and bloating. These symptoms prevent patients from focusing on their daily activities, but successful management is possible. Besides lifestyle adjustments, medications can also provide much-needed relief. These medications include:
- Antispasmodics – medications used for muscle relaxation. They work to relieve cramps, pain, and discomfort. Antispasmodic drugs used for IBS are:
- Bentyl (Dicyclomine) – relieves spasms in the gastrointestinal tract through smooth muscle relaxation. Not many studies have been conducted on this subject, but available evidence confirms Dicyclomine was more effective than placebo in improving the overall condition of the patient, decreasing abdominal pain, tenderness, and improving bowel habits
- Levsin (Hyoscyamine) – provides relief from muscle spasms including in your digestive tract
- Peppermint oil – used for a wide array of purposes and it is considered one of the most beneficial natural approaches for IBS relief. The underlying mechanisms are poorly elucidated, but it could be down to the relaxing effects of peppermint oil
- Antidepressants – they balance neurotransmitters in the brain to improve connections between brain cells and also to repair the gut-brain relationship. Through their potential to improve relaxation and act on stress, anxiety, antidepressants can also calm your stomach and tackle pain. They work to reduce visceral hypersensitivity which is behind pain and discomfort. The impact of different types of antidepressants on abdominal pain and bloating is poorly understood, but it is generally believed that all three kinds can be helpful
- Tricyclic – amitriptyline (Elavil), Nortriptyline, imipramine
- SSRIs – citalopram, fluoxetine (Prozac), Paroxetine (Paxil), Sertraline (Zoloft), Escitalopram (Lexapro)
- SNRIs – Venlafaxine (Effexor), Duloxetine (Cymbalta), Desvenlafaxine (Pristiq), Milnacipram (Savella)
- Antibiotics – they slow down or destroy the growth of bacteria, and it’s important to mention antibiotics don’t treat viruses such as cold or flu.
- Gut-specific antibiotics – rifaximin (xifaxan) is considered the best and most effective antibiotic for patients with IBS because it acts on the gut specifically. On the other hand, other antibiotics that are used don’t work specifically on your digestive system. Not only is rifaximin effective for treatment of diarrhea, but it is also considered safe with minimum side effects and drug interactions.
Although irritable bowel syndrome is an uncomfortable condition, there are many things patients can do to feel better. Throughout this post, you’ve had the opportunity to learn more about the medications used for this purpose. Prior to using these medications, consult your doctor.
G&H Which medical therapies are currently available to treat irritable bowel syndrome?
MC Most of the currently available treatment options for irritable bowel syndrome (IBS) focus on relieving individual symptoms. Patients with constipation-predominant IBS (IBS-C) may be administered osmotic laxatives, including polyethylene glycol substances; guanylate cyclase-C agonists, such as linaclotide (Linzess, Ironwood Pharmaceuticals/Allergan) and plecanatide (Trulance, Synergy Pharmaceuticals); or a chloride channel activator, such as lubiprostone (Amitiza, Takeda Pharmaceuticals America, Inc.).
Patients with diarrhea-predominant IBS (IBS-D) are treated with opioids; loperamide is the standard over-the-counter medication. Eluxadoline (Viberzi, Allergan Holdings) recently received approval from the US Food and Drug Administration (FDA), and alosetron, a 5-HT3 antagonist, is an older drug that was approved for IBS-D. Importantly, both eluxadoline and alosetron are associated with warnings from the FDA regarding risks of pancreatitis, especially in patients with prior cholecystectomy or ischemic colitis, respectively.
Medications used to treat pain associated with IBS-D (ie, antidepressants and pain modulators) are centrally acting, meaning they work in the central nervous system. This analgesic approach works on the brain to try to reduce the pain arising in the gut. Of note, these medications are not approved to treat the pain of IBS and, thus, are used off-label.
Symptoms revolving around bloating and distention may be treated with diets, including the low–fermentable oligo-, di-, and monosaccharide and polyol diet, as well as antibiotics and probiotics. However, the evidence supporting the use of these approaches is relatively limited given the small clinical trials in which they have been tested, compared to the large trials that have tested the other pharmacologic agents previously mentioned.
G&H Why are new therapies needed for IBS?
MC New therapy is needed particularly in the area of pain relief, as the medications that are currently in use target the pain’s sensory mechanisms in the brain as opposed to the pain arising within the gastrointestinal tract. Antidepressants and centrally acting analgesics may affect the functions of the central nervous system, leading to changes in cognition, level of awareness, and somnolence, among other potential adverse effects. Pain modulators or analgesics that target predominantly, if not exclusively, the gastrointestinal tract (ie, visceral analgesics) rather than the central nervous system would be beneficial.
G&H What therapeutic agents are in the pipeline for IBS?
MC At least 4 therapeutic agents are now in the pipeline for the treatment of IBS. The first is a sodium/hydrogen exchanger inhibitor (tenapanor, Ardelyx) indicated for patients with IBS-C; tenapanor works by inhibiting sodium uptake in the colonic mucosa to alter the fluidity of content in the bowel. Another agent in the pipeline is a neurokinin-2 receptor antagonist (ibodutant, The Menarini Group) and employs a visceral analgesic approach for use in patients with IBS-D. Phase 2B trials have been completed with this medication. A third agent that is being explored presently in single-center studies in Europe is the histamine H1-receptor antagonist ebastine, which works as a visceral analgesic based on proof-of-concept studies in animals and humans. There are other nonsedating antihistaminics available as over-the-counter medications in the United States. If this agent demonstrates success, it has the potential to reduce pain sensation arising in the gastrointestinal tract without causing central side effects such as sedation. The last agent is a biomarker-therapeutic combination that includes a screening blood test (eg, serum C4 or serum FGF19) and offers a diagnostic approach to identify bile acid diarrhea among patients presenting with IBS-D. There is now fairly good evidence that 1 in 4 patients with IBS-D has abnormalities in bile acid metabolism or absorption, and screening blood tests could be used to identify patients who have an abnormality in bile acid homeostasis or synthesis. The positive diagnosis would then be combined with a bile acid sequestrant (eg, cholestyramine, colestipol, colesevelam ) or a farnesoid X receptor agonist such as obeticholic acid (Ocaliva, Intercept), a drug currently approved for the treatment of primary biliary cholangitis. This combined diagnostic and therapeutic approach will indicate the optimal treatment for the individual patient who has bile acid malabsorption rather than empirically treating all patients and hoping for the best.
G&H What do trial data show regarding the safety of these drugs and their adverse effects?
MC The risk of ischemic colitis in patients treated with alosetron is estimated to be about 1 in 800 patients. Through the FDA Adverse Event Reporting System, a surveillance program set up by the FDA, it appears that patients treated with eluxadoline are at risk of developing pancreatitis, although the prevalence is not completely clear. As a result, the FDA issued a warning earlier this year stating that this medication should not be used to treat patients with IBS-D who have had their gallbladder removed. However, it is possible that the medication may induce pancreatitis even in patients who still have their gallbladder in place; indeed, pancreatitis is a known adverse effect of μ-opioid receptor agonists caused by inducing spasm of the sphincter of Oddi. In general, it is important to keep in mind that IBS typically does not result in loss of life or significant adverse consequences or morbidity. The clinical trials that have been conducted have occasionally identified adverse effects with a frequency of only 1 in 500 or 1 in 1000 patients. Thus, there is a distinct possibility, when conducting a phase 3 trial program with 1500 to 2000 patients, that a relatively rare adverse effect may not be identified during the trial.
G&H How do these therapies compare in terms of efficacy?
MC From an efficacy standpoint, it is my perception that the more recently approved drugs appear to have relatively similar efficacy, especially when comparing them using the same clinical trial endpoints. For example, loperamide is very efficacious for diarrhea but has not been proven to be effective for the pain component of IBS-D. However, eluxadoline, which is efficacious for treatment of diarrhea, has not demonstrated a significant effect on pain alone, although there is an effect on the composite endpoint of pain and diarrhea in comparison to placebo. Whereas this efficacy on the composite endpoint may suggest greater benefit compared to loperamide, it is important to note that the older studies conducted with loperamide never appraised the combined endpoint, and, in fact, one trial did show benefit with loperamide on pain relief. Thus, for treating diarrhea alone, eluxadoline and loperamide appear to be similar.
Relative efficacy of drugs for chronic idiopathic constipation (rather than IBS-C) was assessed using network meta-analysis. This suggested that the approved drugs lubiprostone, linaclotide, tegaserod, bisacodyl, and sodium picosulphate and the experimental drugs prucalopride, velusetrag, and elobixibat have similar efficacy for primary endpoints, which were at least 3 complete spontaneous bowel movements (CSBMs) per week and an increase over baseline by at least 1 CSBM per week. Regarding the guanylate cyclase-C agonists or chloride channel activators for IBS-C (ie, plecanatide, linaclotide, lubiprostone), there is similar efficacy for the relief of constipation and possibly lower pain relief with lubiprostone. However, it is important to note that there are no head-to-head comparisons of these medications. Thus, treatment choice is often determined by what the patient can tolerate and the adverse effects associated with each medication. Some studies have claimed that linaclotide causes more diarrhea compared with plecanatide, but the methods for assessing this adverse effect were different in the trials with these 2 drugs, and a strict comparison cannot be made. In addition, linaclotide dose can be titrated lower if the patient experiences diarrhea because there are 3 approved doses that have a beneficial effect on the constipation. A number of patients who receive lubiprostone experience nausea, which can be a factor in determining which medicine to administer to patients with IBS-C.
G&H What do you believe are the most exciting targets in the emerging treatment landscape?
MC I believe that the major unmet need is the pain component of IBS; therefore, the targets that have been most interesting to me are the neurokinin-2 receptor antagonist (ie, ibodutant) and the histamine H1-receptor antagonist (ie, ebastine), which appear to be more specific for peripheral targets of visceral pain. These emerging areas will hopefully transpire into beneficial options for treatment of patients with pain in association with IBS.
G&H What is the role of bile acids in patients with IBS, and how do they compare to the use of biomarkers?
MC A systematic review of the literature—based on studies from many countries—shows that, on average, 25% to 33% of patients with IBS-D have evidence of either increased bile acid synthesis or bile acid malabsorption. In the past, patients who showed a poor response to loperamide for the management of diarrhea would be given a trial with a sequestrant for bile acids. The challenge was that bile acid sequestrants are nonspecific and have other effects that may not be related to binding bile acids; therefore, in a patient with symptomatic benefit, it was not certain whether the medicine was treating bile acid malabsorption. The availability of the screening blood tests as biomarkers for bile acid malabsorption (eg, fasting morning serum C4 or serum FGF19) could play a major role in terms of selecting patients for bile acid sequestrant therapy. There is also evidence from studies performed at the Mayo Clinic that there is a subgroup of patients with IBS-C who have a deficiency of bile acids in their colon. It is conceivable that in the future, this might be a patient population in whom clinicians could supplement bile acids in order to normalize colonic function through the action of these natural laxatives. An alternative would be an experimental medication that inhibits the ileal bile acid transporter (eg, elobixibat).
G&H How soon will these drugs be available for clinical use?
MC The medications that are currently in the pipeline are at least 2 or 3 years away from being available because phase 3 trials need to be completed. However, laboratories are now offering measurement of serum C4 and other bile acid biomarkers, and bile acid binders that are approved for other indications are available.
G&H What are the challenges impacting the development of IBS drugs?
MC The biggest challenge throughout the last several decades has been the difficulty in developing a proof-of-concept model for visceral pain in humans that predicts whether a drug will be efficacious in phase 2B and phase 3 clinical trials. The field currently lacks an effective, simple model whereby clinicians can test new drug entities in carefully performed studies in the laboratory to see whether the drugs have an effect on visceral pain. It is likely that this has been a deterrent to quickly screen for the efficacy of visceral analgesics, and, consequently, many drugs have come in and out of development. For example, talnetant and pexacerfont were targeting pain mechanisms through neurokinin- and corticotropin-releasing hormone receptors, and went through large phase 2B or phase 3 trials and eventually were proven not to be efficacious.
G&H What are the priorities of research in this area?
MC One of the main areas needing continued focus is in the relief of visceral pain and the use of peripherally active analgesics. The development of a proof-of-concept model that can be tested in humans would also be a way to advance this field.
Dr Camilleri conducts industry-supported research studies with alosetron, tegaserod, talnetant, pexacerfont, elobixibat, prucalopride, velusetrag, linaclotide, and lubiprostone. However, he has no personal financial conflicts.
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Medication for Irritable Bowel Syndrome in Adults
Abdominal pain and bloating are common symptoms of IBS and may occur along with diarrhea, constipation, or both. Some people find that abdominal pain—which may feel like a deep, aching pain similar to stomach cramps or a sharp, stabbing pain—is the most difficult symptom of IBS. Our physicians can recommend one or more medications to relieve the pain.
For abdominal pain associated with IBS, your physician may recommend a prescription antispasmodic medication to relax the gut muscles, easing pain and discomfort.
Some research suggests that peppermint oil—an extract available at health food stores—may act as a natural antispasmodic agent. Your doctor can determine whether peppermint oil is right for you.
Probiotics are dietary supplements that contain beneficial microorganisms already found in the gastrointestinal tract. If the body’s “good” bacteria become outnumbered by “bad” bacteria as a result of IBS, the digestive system’s microbacterial environment—or gut microbiome—becomes unbalanced. A bacterial imbalance can lead to gas, bloating, and irregular bowel movements.
For some people, probiotic supplements may help restore the right balance of “good” and “bad” bacteria. The dosage varies depending on the type of supplement your physician recommends. Researchers at NYU Langone are leading the way in evaluating the role of the gut microbiome in preventing and treating digestive diseases.
Your doctor may recommend nonabsorbable antibiotics, such as rifaximin, if the results of a hydrogen breath test indicate that you have an overgrowth of bacteria in the intestines. This type of medication is prescribed to target bacteria that cause gas, bloating, and other IBS symptoms.
Unlike other antibiotics, nonabsorbable antibiotics are not absorbed into the bloodstream and body, allowing them to target intestinal bacteria.
Your physician may prescribe this medication, which is taken by mouth, for about 10 days.
When prescribed in low doses, some antidepressant medications may block pain signals that travel between the digestive system and the brain, alleviating abdominal pain. These include tricyclic antidepressants, serotonin–norepinephrine reuptake inhibitors, and selective serotonin reuptake inhibitors.
Even when taken in low doses, these medications may have side effects, including weight gain and mood swings. So it is important that you and your physician schedule regular follow-up appointments to determine the dosage of medication that relieves IBS symptoms without causing side effects.