Medication Education
Gastrointestinal & Gut-Brain Axis Medicines
Amitriptyline (Elavil)
Common Uses:
• Functional dyspepsia (chronic indigestion or stomach discomfort)
• Irritable bowel syndrome (IBS), especially with pain or diarrhea
• Nerve-related pain in the abdomen and digestive tract
Mechanism:
• Adjusts levels of natural nerve messengers, mainly serotonin and norepinephrine, in the brain and spinal cord
• Calms overly sensitive nerve pathways running between the gut and brain to lower stomach pain
• Slows down bowel transit time, which helps reduce diarrhea and cramping
Most Common Side Effects:
• Dry mouth
• Drowsiness
• Weight gain
• Constipation
Black Box Warning: Suicidal Thoughts and Behaviors
• Antidepressants can increase the risk of suicidal thoughts and behaviors in children, teenagers, and young adults up to age 24. Patients should be closely watched for changes in mood, worsening depression, or unusual thoughts.
Buspirone (BuSpar)
Common Uses:
• Functional dyspepsia (upper stomach fullness, early satiety, or discomfort)
• Gastroparesis (delayed stomach emptying)
• Irritable bowel syndrome (IBS)
Mechanism:
• Works on specific serotonin receptors to help relax the upper part of the stomach after eating
• Improves communication along the vagus nerve and enteric (gut) nervous system
• Balances digestive movement and helps lower gut sensitivity
Most Common Side Effects:
• Dizziness
• Nausea
• Headache
Dicyclomine (Bentyl)
Common Uses:
• Irritable bowel syndrome (IBS)
• Functional bowel disorders
• Intestinal spasms and abdominal cramping
Mechanism:
• Blocks acetylcholine, a chemical messenger that triggers muscle contractions in the intestines
• Calms down overactive nerve signals from the vagus nerve to the gut
• Directly relaxes the smooth muscle lining the intestinal walls to relieve cramps
Most Common Side Effects:
• Dry mouth
• Drowsiness
• Blurred vision
• Dizziness
Eluxadoline (Viberzi)
Common Uses:
• Irritable bowel syndrome with diarrhea (IBS-D)
• Chronic functional loose stools
Mechanism:
• Attaches to specialized opioid receptors located throughout the gut nervous system
• Slows down intestinal contractions to allow stool to form normally
• Calms visceral nerves to lessen belly pain and reduce urgent bathroom trips
Most Common Side Effects:
• Constipation
• Nausea
• Abdominal pain
Gabapentin (Neurontin)
Common Uses:
• Chronic nerve-related abdominal pain
• Functional belly pain syndromes
• Gastroparesis-associated discomfort (off-label)
Mechanism:
• Attaches to calcium channels on nerve cells in the central and gut nervous systems
• Decreases the release of extra pain-signaling chemicals between nerves
• Lowers nerve sensitivity and turns down exaggerated pain signals coming from the intestines
Most Common Side Effects:
• Dizziness
• Fatigue and tiredness
• Swelling in the legs or hands
• Weight gain
Hyoscyamine (Levsin)
Common Uses:
• Irritable bowel syndrome (IBS)
• Functional digestive disorders
• Spasms of the colon and bladder
Mechanism:
• Blocks acetylcholine receptors on the nerves supplying the digestive tract
• Shuts down sudden nerve surges that cause sudden muscle spasms
• Relaxes the muscles of the stomach and bowels to ease sudden cramping
Most Common Side Effects:
• Dry mouth
• Blurred vision
• Dizziness
• Constipation
Linaclotide (Linzess)
Common Uses:
• Irritable bowel syndrome with constipation (IBS-C)
• Chronic idiopathic constipation (long-term constipation of unknown cause)
• Functional constipation in children ages 6 to 17
Mechanism:
• Binds to guanylate cyclase-C receptors on the inner surface of the intestines
• Increases fluid flow into the bowels to soften stools and speed up bowel movements
• Helps quiet down pain-sensing nerves in the gut lining to reduce belly aching
Most Common Side Effects:
• Diarrhea
• Belly pain
• Gas and bloating
Black Box Warning: Risk of Serious Dehydration in Pediatric Patients
• Linaclotide is contraindicated (must not be used) in children younger than 2 years of age because it can cause severe, life-threatening dehydration.
Lubiprostone (Amitiza)
Common Uses:
• Chronic idiopathic constipation (CIC)
• Irritable bowel syndrome with constipation (IBS-C) in adult women
• Opioid-induced constipation (constipation caused by prescription pain pills)
Mechanism:
• Turns on specific chloride channels located in the lining of the intestines
• Pulls water and essential fluids into the gut to soften hardened stool
• Naturally triggers muscular contractions to move stool along smoothly
Most Common Side Effects:
• Nausea (taking this medication with meals helps prevent this)
• Diarrhea
• Abdominal pain
Metoclopramide (Reglan)
Common Uses:
• Gastroparesis (poor or delayed stomach emptying)
• Gastroesophageal reflux disease (GERD)
• Nausea and vomiting caused by slow gut motility
Mechanism:
• Blocks dopamine receptors in the stomach and brain to stop feelings of nausea
• Boosts the release of acetylcholine to help the stomach squeeze food downward faster
• Strengthens the lower esophageal valve to keep acid from traveling upward
Most Common Side Effects:
• Drowsiness and fatigue
• Restlessness or a feeling of needing to keep moving (akathisia)
• Diarrhea
Black Box Warning: Tardive Dyskinesia
• Metoclopramide can cause tardive dyskinesia, a serious and often permanent movement disorder causing uncontrollable, repetitive muscle twitches (such as lip smacking, tongue movements, or grimacing). The risk increases with longer treatment and higher lifetime doses; use should not exceed 12 weeks.
Ondansetron (Zofran)
Common Uses:
• Nausea and vomiting from various medical causes
• Gastroparesis-related nausea
• Off-label treatment for chronic diarrhea in IBS-D
Mechanism:
• Blocks serotonin at 5-HT3 receptors found both in the brain's vomiting center and along gut nerves
• Stops vagus nerve triggers that send nausea warnings to the brain
• Slows down colonic movement as a secondary effect, helping firm up liquid stool
Most Common Side Effects:
• Headache
• Constipation
• Fatigue
Pregabalin (Lyrica)
Common Uses:
• Chronic nerve-related abdominal pain
• Functional digestive pain syndromes
• Visceral hypersensitivity (heightened nerve pain in the gut)
Mechanism:
• Strongly attaches to calcium channels on nerve endings throughout the nervous system
• Reduces the surge of excitatory pain chemicals sent between the gut and brain
• Quiets down hyper-reactive intestinal nerves to relieve ongoing gut pain
Most Common Side Effects:
• Dizziness
• Drowsiness
• Swelling in the lower legs or arms
• Weight gain
Rifaximin (Xifaxan)
Common Uses:
• Small intestinal bacterial overgrowth (SIBO)
• Irritable bowel syndrome with diarrhea (IBS-D)
• Traveler's diarrhea
Mechanism:
• Works as a gut-targeted antibiotic that stays almost entirely inside the digestive tract with minimal absorption into the bloodstream
• Stops bacteria from making essential proteins, reducing overall bacterial overgrowth
• Lowers irritating bacterial toxins and inflammation, allowing gut transit and sensitivity to normalize
Most Common Side Effects:
• Mild nausea
• Headache
• Abdominal bloating or gas
Tegaserod (Zelnorm)
Common Uses:
• Irritable bowel syndrome with constipation (IBS-C) in adult women under 65 without heart conditions
• Chronic constipation (historical use)
• Gastroparesis (off-label)
Mechanism:
• Activates 5-HT4 serotonin receptors built into the nervous system of the intestinal wall
• Triggers coordinated muscular reflexes to help push intestinal contents forward
• Increases fluid release into the bowel to relieve constipation and bloating
Most Common Side Effects:
• Diarrhea
• Headache
• Abdominal pain
References
• Drossman, D. A., et al. (2018). Neuromodulators for Functional Gastrointestinal Disorders (Disorders of Gut-Brain Interaction): A Rome Foundation Working Team Report. Gastroenterology, 154(4), 1140–1171.
• Lacy, B. E., et al. (2021). ACG Clinical Guideline: Management of Irritable Bowel Syndrome. The American Journal of Gastroenterology, 116(1), 17–44.
• Camilleri, M., et al. (2022). ACG Clinical Guideline: Gastroparesis. The American Journal of Gastroenterology, 117(8), 1197–1220.
• Pimentel, M., et al. (2020). ACG Clinical Guideline: Small Intestinal Bacterial Overgrowth. The American Journal of Gastroenterology, 115(2), 165–178.
• U.S. National Library of Medicine / FDA DailyMed. Rockville, MD: U.S. Food and Drug Administration (Prescribing labels and boxed warnings for Amitriptyline, Buspirone, Dicyclomine, Eluxadoline, Gabapentin, Hyoscyamine, Linaclotide, Lubiprostone, Metoclopramide, Ondansetron, Pregabalin, Rifaximin, and Tegaserod).
Polyethylene Glycol (Miralax)
Polyethylene Glycol (Miralax) is a safe, gentle osmotic laxative which pulls water into the colon, softens stool, hopefully triggering bowel movements.
Many patients come to see us already having tried this on an as needed basis. Some specialists recommend routine dosing.
I often tell patients that miralax is great, safe, but doesn't care if you have bloating or abdominal pain. It is like a blunt hammer that will soften it even liquify hard stool, stimulating your colon to get it out.
Most commonly seen side effects are diarrhea or Intolerance. No commonly known evidence of harm if used long term.
Docusate (Dulcolax)
Docusate (Dulcolax) is a stool softener, emollient laxative. Okay for mild constipation but lacks data backing it in serious long term constipation like IBS-C and CIC.
