Chronic Diarrhea: Diagnosis and Management

Lawrence R. Schiller; Darrell S. Pardi; Joseph H. Sellin


Clin Gastroenterol Hepatol. 2017;15(2):182-193. 

In This Article

What Empiric Treatments Can Be Used for Symptomatic Management?


25. Opiate antidiarrheals are a mainstay of symptomatic management when specific treatment is not possible. Dosing should be scheduled rather than as needed. (1b)

Ideally, a work-up for chronic diarrhea will lead to a specific diagnosis and treatment. However, that is not always the case. Empiric treatment is necessary when testing does not find a specific diagnosis, when a specific diagnosis has no specific treatment, or treatment has failed. There are several options for empiric therapy (Supplementary Table 4); however, opiates are generally the first choice. Other "constipating" medicines may help individuals with chronic diarrhea.[79]

Opiates. Treatment with opiates is effective and safe. Loperamide is μ-receptor agonist primarily affecting intestinal motility.[80] Like all opiates, it slows intestinal transit time and increases net absorption. With minimal penetration into the brain, it has little potential for abuse. In chronic diarrhea, scheduled dosing is recommended. For example, if diarrhea occurs after meals, dosing before meals is used. Morning-predominant diarrhea can be improved by bedtime or early morning dosing.

Diphenoxylate and difenoxin have similar potency as loperamide but cross the blood-brain barrier and may produce central nervous system effects, especially at high doses. The potential for abuse is limited by combining these drugs with atropine.

More potent opiates are the most effective antidiarrheal drugs but are not prescribed frequently because of concern about misuse. Codeine, opium, or morphine preparations (eg, paregoric, tincture of opium, and morphine) can be very useful for severe diarrhea, such as that resulting from bowel resection. The potential for abuse can be minimized by informing the patient about the risk of abuse, by starting with a low dose and titrating the dose gradually upward, and by refilling prescriptions only when the anticipated volume should have been used.

Other Drugs. Bile acid binding resins (cholestyramine, colestipol, colesevelam) are effective in BAM[74] but also have nonspecific constipating effects. They also may bind other medications, and the dosing schedule should ensure that they are taken more than 2 hours away from other medications. Neither antibiotics nor probiotics are useful as nonspecific therapy in chronic diarrhea.

Clonidine, an α2-adrenergic agonist drug that simulates absorption and slows intestinal transit, is used for diabetic diarrhea that is due to a loss of noradrenergic innervation.[81] It also may be useful in the diarrhea of opiate withdrawal. However, its use is often limited by its antihypertensive effect. Anticholinergic medications used to treat other conditions may mitigate diarrhea. For example, tricyclic antidepressants used to manage depression or pain may treat coexisting diarrhea.

Octreotide is used to treat diarrhea in patients with carcinoid syndrome or VIPomas, chemotherapy-induced diarrhea, HIV, and dumping syndrome after gastric surgery.[82] It also has been tried as empiric therapy for nonspecific diarrhea, with mixed results. For this reason and its cost, empiric use of octreotide in nonspecific diarrhea is not recommended.

For small volume watery diarrhea and fecal incontinence, fiber supplementation or a hydrophilic, poorly fermentable colloid (calcium polycarbophil, carboxymethylcellulose) sometimes may be helpful.[83] Soluble fibers such as pectin increase the viscosity of luminal contents, slow gastric emptying, and slow intestinal transit. None of these agents reduce stool weight. However, a change from watery to semi-formed stool may alleviate symptoms.

Oral calcium supplementation also may treat mild chronic diarrhea. Bismuth subsalicylate is a frequently used over-the-counter treatment for diarrhea; however, there is some concern for safety with prolonged use. Bismuth also may be effective in the treatment of microscopic colitis.[84]

Alosetron is a serotonin type 3 antagonist that slows colonic transit and increases fluid absorption.[85] It is useful in diarrhea-predominant IBS and functional diarrhea, but because of a risk of colonic ischemia and severe constipation, it is used infrequently. Another drug approved for IBS with diarrhea is the μ-opiate receptor agonist, eluxadoline.[86] It is unknown whether alosteron or eluxadoline has a beneficial effect in diarrhea that is not due to IBS.

Crofelemer, a chloride channel antagonist, is approved for the treatment of HIV-associated diarrhea but may be of use in a variety of diarrheal diseases in which the cystic fibrosis transmembrane receptor chloride channel is active.[87] However, this has not been tested.

There is no simple and logical algorithm to govern the empiric treatment of chronic diarrhea in every patient. Therefore, a thoughtful trial and error approach is frequently required to find the most effective therapy or combination of therapies for each patient.

A summary of all our recommendations is provided in Table 3 .