What medication can increase appetite in a patient with Irritable Bowel Syndrome with Diarrhea (IBS-D) and a negative colonoscopy?

Medication to Increase Appetite in IBS-D with Negative Colonoscopy

Mirtazapine is the most appropriate medication to increase appetite in patients with IBS-D, as it directly addresses poor appetite while simultaneously treating multiple IBS-associated symptoms including diarrhea, abdominal pain, and insomnia. 1, 2, 3

Primary Recommendation: Mirtazapine

Mirtazapine should be started at 15 mg once daily at bedtime, with potential titration to 45 mg once daily based on response and tolerability. 1, 2

Rationale for Mirtazapine in IBS-D with Poor Appetite

• Mirtazapine is specifically noted to cause increased appetite and weight gain as a common side effect, making it uniquely suited for patients with appetite concerns 2
• The 2021 AGA guideline on chronic GI pain management identifies mirtazapine as having "greater effects on early satiety" and demonstrates "significant improvements in pain-free days" in IBS patients 1
• Recent evidence supports mirtazapine as a "one-stop treatment" for multiple IBS symptoms including diarrhea, poor appetite, insomnia, nausea, and abdominal pain 3
• Unlike tricyclic antidepressants (TCAs), mirtazapine's side effect profile includes increased appetite rather than appetite suppression 1, 2

Dosing and Titration

• Start at 15 mg once daily at bedtime 1
• Titrate according to response and tolerability to a maximum of 45 mg once daily 1
• Appetite stimulation effects typically occur early in treatment 2
• Monitor for treatment response at 3-6 weeks 1

Important Safety Considerations

• Monitor for suicidal thoughts and behaviors, especially during initial treatment and dose changes 2
• Screen for agranulocytosis risk: discontinue immediately if sore throat, fever, stomatitis, or infection develops with low WBC count 2
• Avoid concomitant use with MAOIs due to serotonin syndrome risk 2
• Exercise caution in patients with cardiovascular disease or QT prolongation risk factors 2
• Common side effects include sedation, constipation or diarrhea, anxiety, nausea, headache, and fatigue 1

Alternative Approach: Tricyclic Antidepressants (with Caveat)

If mirtazapine is contraindicated or not tolerated, TCAs can be considered for IBS-D symptom management, though they typically cause appetite suppression rather than stimulation 1

TCA Dosing for IBS-D

• Start amitriptyline 10 mg at bedtime 1
• Titrate by 10 mg weekly or biweekly to 30-50 mg at bedtime based on response 1
• TCAs improve global symptoms and abdominal pain in IBS-D 1
• However, TCAs commonly cause reduced appetite as a side effect, making them suboptimal for patients with appetite concerns 1

Concurrent IBS-D Symptom Management

While addressing appetite, continue standard IBS-D management:

First-Line Antidiarrheal Therapy

• Loperamide 4-12 mg daily for stool frequency and urgency control 1, 4
• Limited effect on abdominal pain but effective for diarrhea 1

Second-Line Options (if symptoms persist)

• Ondansetron (5-HT3 antagonist): start 4 mg once daily, titrate to maximum 8 mg three times daily 1, 4
• Eluxadoline 100 mg twice daily (contraindicated in cholecystectomy, sphincter of Oddi problems, alcohol dependence, pancreatitis, severe liver impairment) 1, 4
• Rifaximin 550 mg three times daily for 14 days 1

Critical Pitfalls to Avoid

• Do not use SSRIs as primary therapy for appetite stimulation in IBS-D - they commonly cause reduced appetite and nausea, and evidence for IBS efficacy is weak 1
• Avoid anticholinergic antispasmodics (e.g., dicyclomine) in patients with appetite concerns - they may worsen appetite through anticholinergic effects 4
• Do not prescribe appetite stimulants used in other conditions (e.g., dronabinol, megestrol acetate) without addressing underlying IBS-D pathophysiology 1
• Ensure negative colonoscopy has adequately ruled out organic disease including microscopic colitis, celiac disease, and inflammatory bowel disease before attributing symptoms to IBS-D 1

Patient Counseling Points

• Clearly explain that mirtazapine is being used as a "gut-brain neuromodulator" to treat IBS symptoms and appetite, not as an antidepressant 1
• Appetite improvement may occur within days to weeks 2
• Sedation is common initially but often improves with continued use 1
• Weight gain is expected and desired in this clinical context 2
• Reevaluate effectiveness at 3-6 weeks and adjust therapy accordingly 1