What is the best treatment approach for a patient with functional abdominal pain, potentially accompanied by underlying anxiety or depression?

Treatment of Functional Abdominal Pain

For functional abdominal pain with underlying anxiety or depression, start with an SSRI (sertraline 25 mg or escitalopram 5-10 mg daily, titrating slowly over 2-4 weeks) as first-line pharmacotherapy, combined with gut-directed cognitive behavioral therapy or hypnotherapy, while avoiding restrictive diets in patients with significant anxiety. 1, 2

Initial Assessment Priorities

Before initiating treatment, screen for specific red flags and comorbidities:

• Check tissue transglutaminase IgA and total IgA to exclude celiac disease, which commonly presents with abdominal pain and bloating 3
• Screen for anxiety and depression using validated tools (Hospital Anxiety and Depression Scale), as 54% of youth with functional abdominal pain have clinically significant anxiety symptoms 4, 5
• Obtain plain abdominal radiography during acute episodes to exclude bowel obstruction and other structural pathology 2
• Assess for alarm features including weight loss >10%, GI bleeding, family history of IBD, nocturnal symptoms that wake from sleep, or fever—these require endoscopy and imaging 3, 1

Treatment Algorithm Based on Psychiatric Comorbidity

When Moderate-to-Severe Anxiety or Depression Dominates

Start with SSRIs as first-line therapy when psychiatric symptoms are prominent:

• Begin sertraline 25 mg or escitalopram 5-10 mg daily, titrating slowly over 2-4 weeks to minimize initial GI side effects 1
• Counsel patients upfront that nausea and diarrhea may occur initially but typically resolve within 1-2 weeks, as this reduces medication-related anxiety and improves adherence 1
• Add ondansetron 4-8 mg twice or three times daily as needed for breakthrough nausea during SSRI titration 1
• Expect psychiatric benefits at 4-6 weeks, with GI neuromodulatory effects potentially occurring sooner at 2-4 weeks 1
• If SSRI adequately treats psychiatric symptoms but GI pain persists, add low-dose TCA (nortriptyline 10-30 mg at bedtime) for additional gut-brain neuromodulation 1

Critical pitfall: Low-dose TCAs (10-50 mg) are inadequate as monotherapy for moderate-to-severe depression or panic disorder, which require therapeutic antidepressant doses (typically 150-200 mg for TCAs) 1, 2

When Abdominal Pain is Predominant with Mild Psychiatric Symptoms

Start with low-dose tricyclic antidepressants when pain is the primary complaint:

• Begin amitriptyline or nortriptyline 10 mg at bedtime, titrating by 10 mg weekly to 30-50 mg 1, 2
• TCAs have the strongest evidence for reducing abdominal pain (RR 0.53,95% CI 0.34-0.83) 1
• Analgesic effects occur at lower doses than required for mood effects 2
• Antispasmodic medications, particularly anticholinergic agents, can be added when symptoms are exacerbated by meals 6, 2

Essential Psychological Interventions

Integrate brain-gut behavioral therapies alongside pharmacotherapy for optimal outcomes:

• Cognitive behavioral therapy, gut-directed hypnotherapy, and mindfulness therapy have strong evidence for abdominal symptoms in functional GI disorders 6, 2
• Initiate psychological treatments when symptoms impair health-related quality of life, regardless of severity 2
• Refer to a gastropsychologist if moderate-to-severe anxiety symptoms persist, quality of life is significantly impaired, or avoidance behaviors interfere with treatment adherence 1
• Psychological therapies are particularly valuable in patients with high anxiety, as they effectively reduce both GI symptoms and anxiety with large effect sizes (generalized anxiety disorder: Hedges g = 1.01) 1

Dietary Management Strategy

Dietary approach must be tailored to psychiatric comorbidity:

• Do NOT implement strict low-FODMAP diet in patients with severe anxiety, as dietary restriction may worsen health anxiety and eating pathology 1
• For patients without significant anxiety, implement low-FODMAP diet for 4-6 weeks as initial therapeutic intervention under dietitian supervision to ensure nutritional adequacy 3, 2
• In patients with self-reported gluten sensitivity, fructans rather than gluten often cause symptoms—consider eliminating fructans specifically 6, 3
• For patients with substantial psychological symptoms, consider Mediterranean diet as it may benefit both mood and GI symptoms without restrictive nature 1

Medications to Avoid

Never use opiates for chronic abdominal pain management—they increase risk of dependence, overdose, and worsen GI symptoms long-term 6, 2

Avoid benzodiazepines for long-term management despite efficacy for acute anxiety, as they have weak treatment effects for panic disorder, potential for physical dependence, and do not address depression or GI symptoms 1

Symptom-Specific Adjunctive Therapies

For patients with specific bowel symptoms alongside pain:

• For diarrhea: loperamide 2-4 mg up to four times daily to reduce loose stools and urgency 2
• For constipation: increase dietary fiber to 25 g/day, though evidence for pain reduction is mixed 2
• Bile acid sequestrants for presumed bile acid diarrhea in patients with ileal disease or resection 6, 3

Treatment Monitoring and Escalation

• Reevaluate patients after 3-6 weeks of initial treatment 2
• If symptoms persist despite 12 weeks of optimized therapy, refer to gastroenterology with motility expertise 3
• For severe and refractory symptoms, referral to multidisciplinary pain center may be beneficial 2
• Combination therapy with different neuromodulators can be considered for severe pain, while monitoring for serotonin syndrome 2

Special Considerations

The pathophysiology of functional abdominal pain is primarily amplified central perception of normal visceral input, rather than enhanced peripheral stimulation from abdominal viscera 7, 8. This central sensitization mechanism explains why neuromodulators (TCAs, SSRIs) and psychological therapies targeting central pain processing are more effective than peripheral treatments.

Anxiety and depression are linked to functional abdominal pain independent of IBS diagnosis, occurring even in otherwise healthy people with subtle GI symptoms 5. This underscores the importance of screening for and treating psychiatric comorbidities in all patients with functional abdominal pain.