Medications for IBS

Any product taken for a therapeutic effect should be considered a drug. Use of medications for IBS, whether prescription, over-the-counter, herbs, or supplements should be considered carefully and in consultation with your healthcare provider.

First-line treatment has traditionally been aimed at treating the most bothersome symptom. This is due to the lack of effective treatment for the overall improvement of multiple symptoms in IBS patients.

However, new therapies for IBS have been recently introduced and have been shown to effectively treat multiple symptoms of IBS. These medications for IBS include:

Laxatives

A laxative is a drug that increases bowel function in patients experiencing constipation.  There are many laxatives available without a prescription.  The most commonly used types include: 

  • Osmotic – polyethylene glycol (PEG) 3350 (such as Miralax®)
  • Stimulant – senna cascara, bisacodyl (such as Dulcolax®, Correctol®)
  • Magnesium-based – milk of magnesia

Of these, only PEG 3350 has been evaluated in clinical trials in people with IBS-C. PEG 3350 has been shown to improve stool texture and frequency (how often someone moves their bowels). This drug does not improve the abdominal pain/discomfort symptoms of IBS. In fact, many people report an increase in their abdominal symptoms when taking this medication. The lack of overall IBS symptom improvement makes this less recommended as a treatment for IBS-C. Common side effects include diarrhea, abdominal cramping, bloating, and nausea. In rarer cases, dehydration and electrolyte disturbances have occurred.

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Antidiarrheals

These are drugs which slow gut transit. They also decrease intestinal secretion (movement of fluid into the intestines) and increase the amount of fluid that is reabsorbed by the gastrointestinal (GI) tract.  

In irritable bowel syndrome (IBS) patients with diarrhea, an antidiarrheal agent such as loperamide is a drug which slows gut transit. 

Loperamide (e.g., Imodium) is available over-the-counter (OTC) and is the most commonly used antidiarrheal. This drug works by bonding to μ-opioid receptors in the GI tract resulting in the changes mentioned above. Similar to OTC laxatives, a few studies have shown that it solidifies loose stools and reduces the frequency of diarrhea. However, it has not been shown to have a beneficial effect on abdominal pain or discomfort.

Side effects associated with Loperamide include

  • abdominal pain and
  • constipation which can become severe.

Discontinue use if constipation develops and be sure to contact your healthcare provider. 

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Secretagogues/Prosecretory agents 

Secretagogues/Prosecretory agents are a class of drugs which increase fluid secretion and movement in the GI tract. These drugs also can improve pain, discomfort, and bloating. Currently there are 4 FDA approved treatments in this class: lubiprostone, linaclotide, plecanatide, and tenapenor.

  • Lubiprostone (Amitiza®) works through the activation of chloride channels in the bowel. This leads to increased bowel movement frequency. While the direct mechanism of pain relief is not known, lubiprostone has been proven to relieve overall IBS symptoms in multiple trials.
    • It is currently FDA approved specifically for use in women. This is due to the limited numbers of men that were enrolled in the initial trials. This drug has proven to be effective in men as well.
    • Common adverse events include nausea and diarrhea. Lubiprostone is also FDA approved for the treatment of chronic idiopathic constipation (CIC) and opioid induced constipation (OIC) for people with chronic non-cancer pain related illnesses.
  • Linaclotide (Linzess®) and Plecanatide (Trulance®) work by increasing fluid secretion and gut movement. Both have also been shown to reduce abdominal pain by decreasing activity of pain sensing nerves. Both drugs treat overall IBS-C symptoms and are FDA approved for the treatment of IBS-C and CIC. Both improve abdominal and stool symptoms within the first week; however, their maximum effect on pain can take longer to appear.
    • The most common side effect experienced by people taking linaclotide or plecanatide is diarrhea. These drugs have minimal systemic absorption,
      providing minimal risk of drug-drug interactions. Systemic absorption refers to a drug that takes effect on the whole body, rather than a specific area.
  • Tenapenor (Ibsrela®) promotes gut motility and secretion. Early trials with this drug suggest that it also reduces pain. The most common side effects noted in clinical trials include diarrhea, abdominal distention, and flatulence. IBSRELA is now available in the US. 

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Antispasmodics 

Antispasmodics are drugs that inhibit smooth muscle contractions in the GI tract.

There are three major classes of antispasmodics:

Anticholinergics

Anticholinergics reduce spasms or contractions in the intestine. This provides the potential to reduce abdominal pain and discomfort. The most common anticholinergics include hyoscyamine (Levsin®, NuLev®, Levbid®) and dicyclomine (Bentyl®). These can be taken daily or as needed. Each dose should be taken 30-60 minutes prior to a meal. Both drugs can be taken by mouth. Hyoscyamine is also available in a sublingual formulation. The sublingual form is placed under the tongue and allowed to dissolve there. Limited clinical studies suggest that these may improve pain (more specifically cramping) in people with IBS. Their efficacy for improving overall IBS symptoms has not yet been proven. As such, this makes them less attractive treatments for IBS.

Side effects of anticholinergics

The most common side effects include headaches, dry eyes and mouth, blurred vision, rash as well as mild sedation or drowsiness. Overall, these side effects are minimal, making them quite safe to use

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Direct Smooth Muscle Relaxants 

Smooth muscle relaxants are not currently available for use in the United States. These drugs appear more effective for treating overall IBS symptoms than anticholinergics. The direct smooth muscle relaxants found to be effective include cimetropium, mebeverine, otilonium (available in Mexico), pinaverium bromide, and trimebutine. Side effects with smooth muscle relaxants appear to be rare.

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Peppermint Oil

Peppermint oil is generally considered an antispasmodic as it shares similar properties with other medications. However, other traits make this particular agent unique. It causes smooth muscle relaxation by blocking calcium entry into intestinal smooth muscle cells. Calcium triggers muscle contraction, so the lack of calcium results in relaxing intestinal muscles. It also has anti-inflammatory, antigas, and anti-serotonergic properties. Serotonin is a chemical found in the gut that accelerates movement. Limiting the amount of serotonin in the gut may be more effective for people with IBS-D.

Recent studies have shown that it can be used to treat both overall symptoms and pain. This treatment may also be used either daily or as needed. Peppermint oil can be found in the form of teas, drops, gels, and capsules. There have not been any specific trials comparing one form to another. Side effects are uncommon but can include heartburn and nausea. These may be reduced by using a coated form. Coated pills minimize the activity of the peppermint oil in the stomach (IBgard®, Pepogest®).

Side Effects of Peppermint oil

Peppermint oil use can rarely cause skin rashes, headaches, or tremors. In clinical trials, these side effects do not occur more frequently in people taking peppermint oil than in those taking a placebo. A placebo is a pill or treatment with no active ingredients. 

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Types of Antidepressants/Neuromodulators

Antidepressants are neuromodulators that have the ability to impact nerve signaling. This nerve signaling is regulated by chemicals called neurotransmitters. These chemicals are released from nerves and bind to other nerves, muscles, and glands. The result impacts pain signaling and can potentially increase or decrease GI function. These drugs often affect GI symptoms at lower dosages than used to treat depression or anxiety.

Multiple classes of neuromodulators exist. The ones most commonly used to treat IBS symptoms include the tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). There is some agreement across international guidelines that TCAs are effective for treating IBS; however, recommendations for using SSRIs remain conflicted.

Antidepressants are considered a global treatment, meaning that it can help multiple IBS symptoms. Be aware that the effectiveness of various agents differs between individuals and a medication regimen must be carefully chosen by the patient and their healthcare provider.

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Non-absorbable Antibiotics

Rifaximin (Xifaxan ®) is the only antibiotic approved by the FDA for treatment of IBS-D. Its exact mechanism of action is unknown. Studies have suggested that it works by modifying bacterial structure or function in the gut potentially targeting the small intestine. It also appears to have anti-inflammatory properties. Rifaximin improves overall IBS-D symptoms.

Rifaximin is a global treatment, meaning that it can help multiple IBS symptoms. This drug differs from other IBS-D treatments as it is only taken for 2- weeks. If Rifaximin is beneficial, symptom relief should occur following the 2-week treatment. Symptoms may return after the initial treatment, and 2 successive treatments are allowed. It is minimally absorbed and generally well tolerated. The most commonly experienced adverse event is nausea.

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Direct Serotonin Agonists/Antagonists

Serotonin (5-HT) is involved in gut secretion, motility, and sensation. Motility is a term that describes the movement of food through the GI tract. Sensation refers to physical feelings. Serotonin receptors in the GI tract appear to be a good target for treating IBS symptoms. Currently two therapies are Food and Drug Administration (FDA) approved for the treatment of IBS-C and IBS-D.

  • Tegaserod (Zelnorm®) works on the nerves and smooth muscles of the GI tract. It increases gut movement and intestinal secretions. In multiple studies it has been shown to improve pain and bloating. An increase in the number of bowel movements has also been shown.
    • Tegaserod is only approved for women with IBS-C under the age of 65.
    • The women must also have no history of ischemic cardiovascular events or more than one cardiovascular risk factor.
    • The most common side effects associated with tegaserod include
          • headaches (migraines),
          • dizziness,
          • back or joint pains.
          • Abdominal symptoms may also occur and include pain, nausea/vomiting, and diarrhea.
    • Tegaserod was first approved by the FDA for the treatment of overall IBS-C symptoms.
    • The drug was voluntarily removed from the market in 2007. This was due to finding a small but increased risk of cardiovascular events such heart attack, stroke, and transient ischemic attacks.
    • In April 2019, the FDA approved the re-introduction of tegaserod for women < 65 with IBS-C as previously described after subsequent studies failed to identify a major link between the drug and increased risks for cardiovascular events in this population.

  • Alosetron (Lotronex ®) delays gut movement and reduces pain. It was first approved by the FDA for the treatment of overall symptoms of IBS-D in women.
    • This drug was withdrawn from the market by the FDA in 2001.
    • Alosetron was found to cause increased rates of severe constipation and ischemic colitis (decreased blood flow to the colon).
    • The FDA re-introduced this drug in 2002 under a Risk Evaluation and Mitigation Strategy (REMS) program.
    • Now, only women with severe IBS-D symptoms can be approved for this drug.

Talk with your healthcare provider to see if these medications are right for you.

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Investigational Agents

Multiple other agents have been tested in small trials
for the treatment of IBS. These include:

• Bile-acid binding agents such as cholestyramine, colestipol, and colesevelam. This group of drugs has been investigated for IBS-D. Symptoms are often similar between bile acid malabsorption (BAM) and IBS-D. 

• Ondansetron (Zofran®) is a highly selective 5-HT3 receptor blocker. It has also been evaluated for the treatment of IBS-D. While less studied, it appears to work like alosetron without the increased risk of severe constipation or ischemic colitis.

• Pregabalin (Lyrica®) is a calcium channel α2δ ligand. Pregaballin has been shown to improve pain, bloating and diarrhea symptoms in a small study of IBS patients.

• Fecal microbial transplants (FMT) – FMT is not specifically a drug, but a treatment. These are also being studied for the relief of IBS symptoms. A recent analysis of 3 studies offered conflicting results. This suggests that the bacteria used, route of administration of the bacteria, and specific IBS subtype may all play a role in symptom response. Fecal transplants are not currently recommended for treating IBS symptoms.

• Cannabinoids: There is currently no data to support the use of cannabinoids for treating IBS.

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Summary

  • Advancements in our knowledge of the causes of IBS continues to lead to many effective treatment options.
  •  Treatments can now improve both the pain/discomfort and bowel symptoms experienced by people with IBS.
  • There is no cure for IBS. Choosing an appropriate treatment should be a decision made between healthcare provider and patient. It is important to have an open discussion weighing the pros and cons of each therapy.

Adapted from IFFGD Publication #168, “Current Pharmacologic Treatments for Adults with Irritable Bowel Syndrome”. By: Darren M. Brenner, MD, Associate Professor of Medicine and Surgery, Northwestern University – Feinberg School of Medicine, Chicago, Illinois; Adapted from an article by: Tony Lembo, MD, Professor, of Medicine and Rebecca Rink MS, Beth Israel Deaconess Medical Center, Harvard Medical School, MA; Edited by: Lin Chang, M.D., Professor of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA

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