Pharmacological Management of Irritable Bowel Syndrome With Constipation (IBS-C)
Based on guidelines from the American Gastroenterological Association. Expert content provided by Morgan Allyn Sendzischew Shane, MD, MSCTI.
Treatment
Treatment: IBS-C
In patients with IBS-C, the AGA recommends using linaclotide.
Strong recommendation
High quality evidence
In patients with IBS-C, the AGA suggests using tenapanor.
Conditional recommendation
Moderate quality evidence
In patients with IBS-C, the AGA suggests using plecanatide.
Conditional recommendation
Moderate quality evidence
In patients with IBS-C, the AGA suggests using lubiprostone.
Conditional recommendation
Moderate quality evidence
In patients with IBS-C, the AGA suggests using polyethylene glycol (PEG) laxatives.
Conditional recommendation
Low quality evidence
In patients with IBS-C, the AGA no longer recommends the use of tegasarod (Zelinorm).
Conditional recommendation
Moderate quality evidence
Treatment (all IBS subtypes)
In patients with IBS, the AGA suggests using tricyclic antidepressants (TCA).
Conditional recommendation
Low quality evidence
In patients with IBS, the AGA suggests against using selective serotonin reuptake inhibitors (SSRI).
Conditional recommendation
Low quality evidence
In patients with IBS, the AGA suggests using antispasmodics.
Conditional recommendation
Low quality evidence
Recommended Dose
Dose
290 mcg daily is the recommended dose for linaclotide (Linzess).
50 mg BID is the recommended dose for tenapanor (Ibsrela).
3 mg daily is the recommended dose for plecanatide (Trulance).
8 mcg BID is the recommended dose for lubiprostone (Amitiza).
17 grams daily is the recommended dose for polyethylene glycol (MiraLAX).
Dose (all IBS subtypes)
Different tricyclic antidepressants (TCAs) can be used, including amitriptyline, nortriptyline, and desipramine. 10-25 mg at bedtime is the recommended starting dose, which can gradually be increased up to 100 mg at bedtime, if needed.
Commonly used antispasmodic medications include dicyclomine and hyoscyamine. Dosing may vary.
SSRI dosing can range from 10-40 mg daily. Recommended dosing for escitalopram is 5-20 mg daily. Recommended dosing for sertraline and fluvoxamine is 50-150 mg daily.
Mechanism of Action
Mechanism of Action (MOA)
Linaclotide is a guanylate cyclase-C agonist which activates CFTR in the gut, increasing intestinal fluid secretion, and inhibits visceral sensory afferent nerves.
Tenapanor inhibits intestinal sodium-proton exchanger 3 (NHE3) in the gut, leading to decreased sodium absorption and increased intestinal fluid secretion, and decreases visceral hypersensitivity.
Plecanatide is a guanylate cyclase-C agonist which activates CFTR in the gut, increasing intestinal fluid secretion, and inhibits visceral sensory afferent nerves.
Lubiprostone activates CIC-2 chloride channels in the gut, increasing intestinal fluid secretion.
Polyethylene glycol (PEG) is an osmotic laxative.
Mechanism of Action (all IBS subtypes)
TCAs are serotonin and norepinephrine reuptake inhibitors and antagonize cholinergic and histamine-1 receptors. Peripheral and central actions which can affect motility, secretion and sensation.
Antispasmodics can be cholinergic, muscarinic, or calcium channel blockers, which relax smooth muscle in the gut.
Selective serotonin reuptake inhibitors work at receptors in the brain and gut.
Side Effects
Side Effects
When prescribing linaclotide, patients should be counseled on the potential for diarrhea.
When prescribing tenapanor, patients should be counseled on the potential for diarrhea and flatulence.
When prescribing plecanatide, patients should be counseled on the potential for diarrhea.
When prescribing lubiprostone, patients should be counseled on the potential for nausea, diarrhea, and abdominal distension.
When prescribing polyethylene glycol (PEG), patients should be counseled on the potential for bloating and diarrhea.
Side Effects (all IBS subtypes)
When prescribing TCAs, patients should be counseled on the potential for dry mouth, sedation, and constipation.
When prescribing antispasmodics, patients should be counseled on the potential for constipation, xerostomia, and visual disturbance.
When prescribing SSRIs, patients should be counseled on the potential for nausea, dry mouth, and diaphoresis.
Expert Commentary
Expert Commentary
When using linaclotide, improvement in abdominal pain may take longer than improvement in bowel habits. Lower doses of 72 and 145 mcg daily are approved for chronic idiopathic constipation (CIC).
Tenapanor is also approved for hyperphosphatemia in chronic kidney disease. Note that improvement in pain may take longer than improvement in bowel habits.
When using plecanatide, improvement in abdominal pain may take longer than improvement in bowel habits. Plecanatide 3 mg daily is also approved for chronic idiopathic constipation (CIC).
A higher dose of lubiprostone 24 mcg BID is also approved for women with chronic idiopathic constipation (CIC) and opioid induced constipation (OIC). It should be taken with meals to reduce nausea.
Polyethylene glycol (PEG) can improve stool consistency, but not abdominal pain.
Expert Commentary (all IBS subtypes)
When prescribing TCAs, secondary amines (desipramine, nortriptyline) may be preferred over tertiary amines (amitriptyline) in patients to minimize sedation and constipation.
Antispasmodics are commonly used in clinical practice to reduce abdominal pain associated with IBS.
The AGA suggests against using SSRIs for primary treatment of IBS. Consider using in patients with coexistent anxiety or depression.
What do the icons mean?
How strong is the AGA's recommendation?
Strong recommendation
Most individuals in this situation would want the recommended course of action, and only a small proportion would not.Conditional recommendation
The majority of individuals in this situation would want the suggested course of action, but many would not.High quality evidence
We are very confident that the true effect lies close to that of the estimate of the effect.Moderate quality evidence
We are moderately confident in the effect estimate. The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.Low quality evidence
Our confidence in the effect estimate is limited. The true effect may be substantially different from the estimate of the effect.Literature
Original/Primary Reference
Other References
Gordon S, Ameen V, Bagby B, Shahan B, Jhingran P, Carter E. Validation of irritable bowel syndrome Global Improvement Scale: an integrated symptom end point for assessing treatment efficacy. Dig Dis Sci. 2003;48(7):1317-1323.American Gastroenterological Association Clinical Decision Support Tool for IBS-C TreatmentChang L, Sultan S, Lembo A, Verne GN, Smalley W, Heidelbaugh JJ. Aga clinical practice guideline on the pharmacological management of irritable bowel syndrome with constipation. Gastroenterology. 2022;163(1):118-136. Supplementary material.
