Medications

A combination of fiber and diet is typically the first step to relieving constipation in patients with IBS-C. If someone has residual constipation despite these measures, the next step is to use an over-the-counter osmotic laxative, which helps draw water into the colon (e.g., polyethylene glycol or magnesium salts like magnesium oxide).

Research suggests that up to 50% of IBS-C patients may still have persistent symptoms after trying first-line therapies such as fiber and over-the-counter laxatives. If a patient is having residual cramping or abdominal pain after normalization of bowel habits, a trial of enteric-coated peppermint oil or a prescription antispasmodic would be the next step. If residual constipation remains despite fiber and/or over-the-counter laxatives, a prescription strength medication to target constipation in IBS-C may be helpful.

The table above summarizes the clinical use of the most commonly prescribed medications for IBS-C. In addition to addressing underlying constipation, these medications have also shown effectiveness in addressing abdominal pain and/or discomfort in patients with IBS. Prucalopride is the only exception and does not improve abdominal pain; for this reason it is only FDA approved for chronic idiopathic constipation but in clinical practice is sometimes used off-label for IBS-C. While the response to constipation symptoms can be assessed within a few days to a week, it can take 4 weeks or more to notice any measurable effect on abdominal discomfort and up to 12 weeks to achieve full effect.

There is a lack of head-to-head trials between these medications, and not all patients will respond to each medication the same way. Therefore, selection of a specific medication depends on a patient's individual symptoms, available dosages, and insurance coverage. For example, linaclotide is available in three dosage capsules (72 mcg, 145 mcg, and 290 mcg), which may provide more flexibility with dosing based on a patient's symptoms than plecanatide, which is only available in one dose (3 mg). Of note, linaclotide is FDA-approved to treat IBS-C using the 290 mcg dose, while the 72 mcg and 145 mcg doses are FDA-approved for chronic idiopathic constipation although many GI providers will use the lower doses to treat patients with IBS-C. Most US-based insurance companies require failure or an insufficient response to another prescription medications for IBS-C prior to approving tenapanor.

A combination of diet and lifestyle therapies are first-line therapies for IBS-D management. If this does not provide adequate symptom control, over-the-counter supplements such as peppermint oil and/or an over-the-counter anti-diarrheal medication such as loperamide can be used as a next step. An alternative to peppermint oil is an antispasmodic medication which is available as a prescription.

Research suggests that up to 40 to 60% of people with IBS-D have persistent symptoms despite first-line therapy and over-the-counter treatments. The next step to consider are prescription-strength options for IBS-D.

The table above summarizes the most commonly prescribed medications for IBS-D, each with a very different mechanism of action. The choice of medication varies significantly based on a patient's individual history and the suspected mechanisms underlying their IBS-D.

Bile acid sequestrants work by binding excess bile acids in the digestive tract. This medication is a good option for patients whose diarrhea is driven by excess bile acids. Patients who have had their gallbladder removed are at increased risk of bile acid diarrhea. Another symptom that suggests a trial of bile acid sequestrants may be effective is when someone reports diarrhea worsens after fatty meals.

Rifaximin is a non-absorbed, gut-specific antibiotic. It's FDA-approved for IBS-D and works by changing the balance of bacteria in the gut. The medication is prescribed as a two-week course and can be repeated up to two additional times.

Eluxadoline is a medication that acts directly on the nerves in the gut to slow down bowel movements and reduce abdominal pain. It is not recommended in individuals with heavy alcohol consumption or a history of gallbladder removal due to the risk of complications.

Neuromodulators such as amitriptyline and nortriptyline are medications prescribed to target the communication between the brain and the gut. These medications also slow GI motility and can be useful to treat diarrhea symptoms. These medications will be discussed in more detail separately.

IBS with mixed bowel habits (IBS-M) can be challenging to treat due to fluctuating bowel habits and the unpredictability of symptoms. The pattern of diarrhea vs. constipation can be helpful in developing a treatment strategy.

For example, for patients with several days of constipation followed by 1-2 days of loose stool, addressing the constipation can reduce episodes of subsequent diarrhea. This approach differs from that of patients who have separate periods of constipation and diarrhea, which should be addressed with individual symptom management based on the bowel habit. For example, an osmotic laxative during periods of constipation, and peppermint oil, an antispasmodic or loperamide as needed during periods of diarrhea.

Research suggests that up to 30 to 50% of patients with IBS continue to have significant abdominal pain or discomfort even after their diarrhea and constipation is well-controlled. In these cases, medications specifically targeted towards helping with pain or discomfort can be effective.

Antispasmodic Medications

Antispasmodic medications work by relaxing the muscles of the intestines. In IBS, the gut often contracts in an exaggerated or uncoordinated way, which can trigger cramping. Medications such as dicyclomine and hyoscyamine are examples of antispasmodic medications. These medications can be taken as needed for symptom relief or preventively before common triggers such as mealtimes. Possible side effects of antispasmodics include urinary retention, dizziness, blurry vision, constipation and dry mouth and should be used with caution in older populations.

Neuromodulators

Central neuromodulators are an effective class of medications used to treat pain in IBS. While many of these medications are traditionally used to treat other conditions such as anxiety and depression, studies have shown they can be effective at treating IBS symptoms.

When a GI provider prescribes a neuromodulator, the goal is to target the communication pathways between the brain and the gut, rather than treating anxiety or depression. For this reason, different medications and doses are used first line compared to the most common medications used to treat psychiatric conditions such as anxiety and depression.

Neuromodulators are typically considered in patients:

• Where pain, bloating or discomfort is the predominant symptom
• With residual abdominal pain or discomfort despite normalization of bowel habits
• With other conditions that overlap with IBS where neuromodulators are also effective therapy such as migraines, fibromyalgia, poor sleep, anxiety, or depression
• With other disorders of gut brain interaction such as functional dyspepsia or functional heartburn
• With diarrhea predominance as many neuromodulators can be effective in addressing diarrhea. Patients with constipation can still be good candidates for neuromodulators for other reasons and different neuromodulator classes vary in effects on gut motility.

Potential side effects of neuromodulators include weight gain, dry mouth, dizziness, sedation, urinary issues, and even sexual dysfunction. Some of these side effects can be minimized by starting at low doses, increasing dosage gradually or switching to a different neuromodulator class.

Neuromodulators can take several weeks to months to achieve sufficient effect and may need to be dose adjusted slowly. Some patients may need to try more than one neuromodulator to find the right medication and dose for their symptoms. For more severe symptoms, neuromodulators can be used in combination with each other. Once symptoms are stabilized on a neuromodulator some patients choose to continue the medication long-term. If stopping the neuromodulator is desired, experts recommend stabilization of symptoms for at least 6-12 months and gradual tapering of the dose to minimize the risk of symptoms recurring.