Gastrointestinal

Functional dyspepsia: outpatient evaluation and management

Clinical Overview and When to Suspect Functional Dyspepsia

— Postprandial fullness

— Early satiation

— Epigastric pain

— Epigastric burning

— Postprandial distress syndrome (PDS): meal-induced fullness or early satiety (most common)

— Epigastric pain syndrome (EPS): pain/burning independent of meals

— Impaired gastric accommodation

— Visceral hypersensitivity to acid/distension

— Delayed gastric emptying (~25%)

— Post-infectious gut–brain axis dysregulation (after gastroenteritis)

— H. pylori low-grade inflammation in a subset

— Chronic upper abdominal symptoms with normal labs and no alarm features

— Symptoms worse with stress, anxiety, or meals

— Frequent overlap with IBS, GERD, and chronic idiopathic nausea

— Vomiting (persistent), Bleeding/anemia, Age ≥60 with new dyspepsia, Dysphagia/odynophagia/weight loss, Worsening or nocturnal pain, family hx upper GI cancer

Board pearl: Functional dyspepsia is a clinical diagnosis of Rome IV criteria + absence of alarm features, not a diagnosis made only after exhaustive negative testing. In a <60-year-old with classic symptoms, no alarms, and negative H. pylori, empiric PPI is both diagnostic and therapeutic—endoscopy is not required upfront.

Key distinction: FD ≠ GERD (heartburn/regurgitation dominant) and ≠ gastroparesis (objective delayed emptying with vomiting/weight loss on scintigraphy). Symptom overlap is the rule, but the dominant symptom drives initial management.

Definition (Rome IV): ≥1 of the following bothersome symptoms for ≥3 months with onset ≥6 months prior, without structural disease on standard evaluation:

Subtypes (overlap is common, ~30%):

Epidemiology: Affects ~10–20% of US adults; one of the top 5 reasons for GI referral. More common in women, smokers, NSAID users, and patients with anxiety/depression.

Pathophysiology (multifactorial):

When to suspect in clinic:

Alarm features ("VBAD-W") that exclude FD until proven otherwise:

Presentation Patterns and Key History

— Postprandial fullness: "I feel full long after meals end"

— Early satiation: "I can't finish a normal-sized meal"

— Epigastric pain: localized between umbilicus and xiphoid, not retrosternal

— Epigastric burning: distinguished from heartburn (retrosternal) by location

— PDS: symptoms within 30 min of eating, worse with fatty/large meals

— EPS: may be independent of meals, sometimes relieved by food or antacids

— Nocturnal symptoms or symptoms that wake the patient → think peptic ulcer, not FD

— IBS symptoms (altered bowel habits, lower abdominal pain) in up to 50%

— GERD symptoms in ~30%

— Chronic nausea, bloating, belching

— Fibromyalgia, chronic pelvic pain, migraines, anxiety/depression

— NSAIDs/aspirin — exclude before labeling functional

— Bisphosphonates, iron, potassium, metformin, GLP-1 agonists, opioids

— Tobacco, alcohol, cannabis (cannabinoid hyperemesis if cyclic vomiting)

— Recent gastroenteritis → post-infectious FD (a recognized subtype)

— PHQ-9, GAD-7 — depression/anxiety prevalence is 2–3× higher in FD

— Adverse childhood events, somatization, current life stressors

— Symptom diary often reveals stress–symptom coupling

Step 3 management: In the outpatient visit, document Rome IV criteria explicitly, screen for alarm features, review a complete medication list, and administer PHQ-9/GAD-7—this single visit drives all downstream decisions (test vs treat H. pylori, empiric PPI, neuromodulator selection, behavioral referral).

Board pearl: A symptom diary linking meals, stress, and bowel habits clarifies subtype (PDS vs EPS) and uncovers overlapping IBS, which changes therapy (add antispasmodic or low-dose TCA rather than escalating acid suppression).

Core symptom clusters to elicit:

Symptom timing and triggers (high-yield history):

Associated functional overlap (ask directly):

Medication and exposure history (must-ask):

Psychosocial screen (Step 3 ambulatory voice):

Physical Exam Findings and Red-Flag Assessment

— Soft abdomen, mild non-specific epigastric tenderness at most

— Normal bowel sounds, no organomegaly, no masses

— Normal weight trajectory, normal vitals

— Weight loss >5% in 6 months — malignancy, malabsorption, gastroparesis

— Pallor or conjunctival pallor — occult GI bleeding/anemia

— Palpable epigastric mass — gastric cancer, pancreatic mass

— Hepatomegaly, ascites, Virchow node (L supraclavicular), Sister Mary Joseph nodule (umbilical) — metastatic gastric cancer

— Jaundice, scleral icterus — pancreaticobiliary disease

— Succussion splash >3 h post-meal — gastric outlet obstruction or gastroparesis

— Murphy sign, RUQ tenderness — biliary disease

— Rectal exam with melena or hematochezia — bleeding source

— Orthostatic vitals if vomiting or poor intake

— BMI trend over visits — falling BMI is an alarm

— Volume status if dehydration suspected

— Carnett sign (tenderness worsens with abdominal wall tensing) → abdominal wall pain, not visceral; avoid endoscopy

— Cardiac exam — atypical angina can mimic epigastric burning, especially in women, diabetics, elderly

— Skin: spider angiomas, palmar erythema → chronic liver disease

Key distinction: A positive Carnett sign localizes pain to the abdominal wall (e.g., anterior cutaneous nerve entrapment, rectus sheath pathology) and excludes functional dyspepsia—trigger-point injection, not PPI, is the answer.

Board pearl: In any patient ≥60 with new dyspepsia or any patient with alarm features on exam, upper endoscopy is mandatory before labeling FD, regardless of how classic the symptom pattern sounds. The exam is your last filter before committing to an empiric strategy.

Expected exam in functional dyspepsia: essentially normal.

Findings that should redirect the workup (NOT functional):

Hemodynamic and nutritional assessment:

Targeted maneuvers worth doing:

Diagnostic Workup — Initial Labs, Imaging, and *H. pylori* Testing

— CBC — screen for iron-deficiency anemia (alarm)

— CMP — liver enzymes, calcium, glucose, renal function

— TSH — hypothyroidism mimics dysmotility

— Celiac serology (tTG-IgA + total IgA) — celiac presents as dyspepsia in ~5%

— Consider HbA1c if diabetes risk (gastroparesis)

— Lipase only if pain pattern suggests pancreatic origin

— Urea breath test or stool antigen — preferred (active infection)

— Hold PPIs ≥2 weeks and antibiotics/bismuth ≥4 weeks before testing (false negatives)

— Serology is not recommended — cannot distinguish active from past infection

— Confirm eradication ≥4 weeks post-treatment with breath/stool test

— RUQ ultrasound only if biliary pain pattern (postprandial RUQ, fatty food intolerance, Murphy)

— CT abdomen reserved for alarm features, weight loss, palpable mass

— Plain films have no role in routine FD workup

Step 3 management: For a patient <60 with dyspepsia and no alarm features, the correct first move is non-invasive H. pylori testing (breath or stool antigen). Treat if positive; if negative or symptoms persist after eradication, proceed to empiric 4–8 week PPI trial. Endoscopy is not first-line in this population.

Board pearl: "Test and treat H. pylori" is cost-effective when local prevalence is >10%—true in most US urban and immigrant-dense populations. In low-prevalence settings, empiric PPI first is acceptable.

Baseline labs (outpatient, all patients with new chronic dyspepsia):

Pregnancy test in any reproductive-age woman before imaging or new medications

H. pylori test-and-treat (cornerstone for patients <60 without alarm features):

Imaging — generally NOT first-line:

ECG: Obtain in any patient ≥40 with epigastric symptoms and cardiac risk factors—silent ischemia in women, diabetics, elderly presents as "indigestion."

Diagnostic Workup — Endoscopy and Advanced Studies

— Age ≥60 with new-onset dyspepsia (per ACG/CAG guidelines)

— Any alarm feature at any age: GI bleeding, iron-deficiency anemia, unintended weight loss, progressive dysphagia, persistent vomiting, palpable mass, family history of upper GI cancer

— Failure of empiric PPI ± H. pylori eradication after 4–8 weeks

— Symptoms in patients from regions with high gastric cancer prevalence (East Asia, parts of Latin America)

— Erosive esophagitis, Barrett esophagus

— Peptic ulcer disease, gastric/duodenal malignancy

— H. pylori (biopsy with rapid urease test or histology)

— Gastric biopsies should sample antrum and body (Sydney protocol) when H. pylori suspected

— Gastric emptying scintigraphy (4-hour solid-phase): if vomiting, early satiety with weight loss, or refractory PDS — diagnoses gastroparesis (>10% retention at 4 h)

— Esophageal pH/impedance: if PPI-refractory symptoms with GERD overlap

— Manometry, EndoFLIP: specialty referral for refractory cases

— MRCP/EUS: only if biliary or pancreatic concern persists

— Breath tests for SIBO: consider in bloating-predominant overlap with IBS

— Routine abdominal CT in young patients without alarms

— Serum gastrin (unless Zollinger-Ellison suspected)

— Repeat endoscopy in <2 years if initial was normal

Key distinction: Gastroparesis requires objective delayed emptying on scintigraphy plus symptoms; functional dyspepsia has normal or only mildly delayed emptying with symptoms driven by hypersensitivity and accommodation. Overlap exists, but the management differs (prokinetics dominate gastroparesis).

Board pearl: A normal EGD in an FD patient is therapeutic—it reduces anxiety and improves symptom scores. Frame it as confirmatory, not negative.

Upper endoscopy (EGD) — indications:

What EGD evaluates:

If endoscopy is normal → diagnosis is functional dyspepsia. Reassure the patient that "normal endoscopy" is the expected finding, not a failed workup.

Selective advanced testing (only when symptoms suggest):

Tests that are generally NOT useful:

Management Logic and Stepwise Algorithm

— Confirm Rome IV criteria, exclude alarms, identify subtype (PDS vs EPS vs overlap)

— Identify modifiable contributors: NSAIDs, smoking, alcohol, large/fatty meals, late-night eating

— Eradicate if positive; ~10% of FD patients have durable symptom relief with eradication alone (the "H. pylori–associated dyspepsia" subset, technically reclassified after sustained response)

— First-line for EPS (epigastric pain/burning predominant)

— Standard-dose once daily, 30 min before breakfast

— Reassess at 4–8 weeks; taper if effective, switch class if not

— First-line for PDS (postprandial fullness/early satiety)

— Metoclopramide (short-term only), or off-label use of low-dose mirtazapine for weight loss/early satiety

— TCAs (amitriptyline, nortriptyline 10–50 mg qhs) — first-line neuromodulator, especially for EPS

— Buspirone 10 mg TID — improves accommodation in PDS

— Mirtazapine 15 mg qhs — early satiety + weight loss + anxiety

— SSRIs not effective for FD per meta-analyses

— Cognitive behavioral therapy, gut-directed hypnotherapy

— Stress reduction, exercise, sleep hygiene

— Dietary: small frequent low-fat meals, limit caffeine/alcohol

Step 3 management: The ambulatory algorithm is test-treat-empiric PPI-neuromodulator-behavioral, escalating every 4–8 weeks. Document response at each visit; do not stack therapies without reassessment.

Board pearl: Subtype-directed therapy matters: EPS → PPI/TCA; PDS → prokinetic/buspirone/mirtazapine. Choosing wrong is a common board distractor.

Step 1 — Diagnostic categorization:

Step 2 — H. pylori test-and-treat (if <60 and no alarms):

Step 3 — Empiric PPI trial (4–8 weeks):

Step 4 — Prokinetic trial:

Step 5 — Neuromodulators (gut–brain agents):

Step 6 — Behavioral and integrative therapies:

Step 7 — Refractory disease: GI referral, consider gastric emptying study, novel therapies (acotiamide where available, STW 5 herbal preparation)

Pharmacotherapy — First-Line Drug Regimens in Detail

— Omeprazole 20 mg, pantoprazole 40 mg, esomeprazole 20 mg, lansoprazole 30 mg — all comparable

— Once daily, 30–60 min before breakfast

— Number needed to treat (NNT) ≈ 10 over placebo in FD

— Trial 4–8 weeks, then attempt taper to lowest effective dose or on-demand use

— Long-term risks (counsel): C. difficile, CAP, hypomagnesemia, B12 deficiency, osteoporotic fractures, AIN, possible CKD progression

— Famotidine 20 mg BID — modest benefit, second-line or PPI-intolerant patients

— Tachyphylaxis within weeks limits chronic use

— Metoclopramide 5–10 mg before meals/qhs — limit to <12 weeks (tardive dyskinesia FDA black-box warning)

— Domperidone (limited US availability, QT prolongation)

— Erythromycin low dose — tachyphylaxis, QT

— Amitriptyline/nortriptyline 10–25 mg qhs, titrate to 50 mg; effective for EPS; counsel anticholinergic side effects, weight gain

— Buspirone 10 mg TID — fundic relaxation, improves accommodation in PDS

— Mirtazapine 15 mg qhs — early satiety, weight loss, comorbid anxiety/insomnia

— SSRIs (e.g., sertraline) — not superior to placebo for FD symptoms but treat comorbid anxiety/depression

— Bismuth quadruple therapy ×14 days (PPI BID + bismuth subsalicylate QID + metronidazole 500 mg QID + tetracycline 500 mg QID) — preferred first-line

— Clarithromycin triple only if known local resistance <15% and no prior macrolide exposure

Board pearl: Metoclopramide carries an FDA black-box warning for tardive dyskinesia—limit to ≤12 weeks, lowest effective dose, document informed consent. This is a favorite Step 3 patient-safety stem.

Key distinction: PPI tachyphylaxis is rare; H2 blocker tachyphylaxis is common within 2–6 weeks—explains why H2 blockers are not maintenance therapy.

Proton pump inhibitors (PPIs) — first-line for EPS:

H2 receptor antagonists:

Prokinetics — first-line for PDS:

Neuromodulators:

H. pylori eradication regimens (US, given clarithromycin resistance >15%):

Expanded Pharmacology — Refractory Therapy and Adjuncts

— Reconfirm diagnosis, re-screen alarms, reassess adherence and timing (PPI must be pre-meal)

— Check for unrecognized NSAID use, cannabis, opioids

— Consider gastric emptying study before adding more drugs

— Switch PPI class (e.g., omeprazole → pantoprazole or dexlansoprazole)

— Add TCA at bedtime to daytime PPI — synergistic for EPS

— Switch from PPI to buspirone or mirtazapine for PDS-predominant

— Combined PPI + prokinetic for overlap subtype

— Pain-predominant + insomnia/anxiety → amitriptyline

— Early satiety + weight loss + anxiety → mirtazapine

— Postprandial fullness without weight loss → buspirone

— Avoid TCAs in narrow-angle glaucoma, urinary retention, severe constipation, recent MI, QT prolongation

— STW 5 (Iberogast) — herbal, multiple RCTs show benefit, watch for hepatotoxicity

— Peppermint oil + caraway oil — improves PDS symptoms

— Rifaximin — if SIBO overlap suspected

— Acotiamide — fundic relaxant, available in Japan/India, not US

— Chronic NSAIDs (substitute acetaminophen/topical)

— Opioids (worsen gastric emptying, opioid-induced dyspepsia)

— Bisphosphonates — switch to IV if essential

— Iron sulfate — switch to gluconate or polysaccharide complex

— CBT and gut-directed hypnotherapy have effect sizes comparable to neuromodulators and should be offered, not reserved for failures

Step 3 management: For PPI-refractory FD, add a low-dose TCA at bedtime before referring to GI. Document a 4–8 week trial at therapeutic dose, screen for QT prolongation with ECG if ≥1 risk factor, and counsel on anticholinergic adverse effects.

Board pearl: SSRIs do not improve FD-specific symptoms even though they treat comorbid depression—choose TCAs, buspirone, or mirtazapine when targeting dyspepsia itself.

When initial PPI or prokinetic fails (after 4–8 weeks at adequate dose):

Second-line / combination strategies:

Neuromodulator selection by phenotype:

Adjuncts with modest evidence:

Drugs to avoid or deprescribe in FD:

Behavioral therapy as a "drug equivalent":

Special Populations — Elderly and Renal/Hepatic Impairment

— Endoscopy is indicated upfront, regardless of alarm features, due to gastric cancer risk

— Lower threshold for imaging if weight loss, anemia, or pain change

— Polypharmacy review essential: NSAIDs, bisphosphonates, SSRIs, anticoagulants, iron, potassium chloride, GLP-1 agonists

— Benefits often still favor use, but deprescribe when possible after symptom control

— Increased risk of C. difficile, hip fracture, pneumonia, hypomagnesemia, B12 deficiency

— Check B12 and magnesium annually in long-term users

— No dose adjustment needed in renal impairment; mild adjustment in severe hepatic impairment (omeprazole, esomeprazole)

— On Beers criteria — strongly avoid amitriptyline; if used, nortriptyline preferred (less anticholinergic)

— Start 10 mg qhs, slow titration; obtain baseline ECG if cardiac history

— Risks: falls, urinary retention, delirium, QT prolongation, orthostatic hypotension

— Higher risk of extrapyramidal symptoms and tardive dyskinesia

— Avoid in Parkinson disease; reduce dose 50% if CrCl <60

— Metoclopramide: reduce dose if CrCl <60

— Famotidine: reduce dose if CrCl <50 (avoid mental status changes, QT)

— PPIs: no adjustment, but monitor for AIN and CKD progression signals

— PPIs metabolized by CYP2C19/3A4 — modest dose reduction in Child-Pugh C

— TCAs heavily hepatically metabolized — start low, titrate slowly

— Buspirone: avoid in severe hepatic impairment

— Mirtazapine: reduce dose by ~30% in moderate-severe hepatic disease

Step 3 management: In any patient ≥60 with new dyspepsia, order EGD before empiric therapy—a frequent Step 3 stem error is jumping to PPI trial in an older patient. Also perform deprescribing review at every visit.

Board pearl: Long-term PPI users ≥65 should have periodic B12, magnesium, and bone density assessment and a documented deprescribing attempt yearly.

Elderly (≥60) with new dyspepsia:

PPI considerations in older adults:

TCAs in elderly — high-risk class:

Metoclopramide in elderly:

Renal impairment:

Hepatic impairment:

Special Populations — Pregnancy, Pediatrics, and Comorbid Psychiatric Disease

— Dyspepsia affects up to 80% of pregnancies, peaks in third trimester (mechanical + progesterone-mediated LES relaxation)

— First-line: lifestyle — small frequent meals, head-of-bed elevation, avoid late meals

— Step 1 pharmacotherapy: calcium carbonate antacids (avoid sodium bicarbonate — metabolic alkalosis, fluid retention; avoid magnesium trisilicate)

— Step 2: sucralfate (Category B, minimally absorbed) — safe in all trimesters

— Step 3: H2 blockers — famotidine preferred (ranitidine withdrawn for NDMA)

— Step 4: PPIs — omeprazole has the most safety data; all are generally considered low-risk

— Avoid: misoprostol (abortifacient), bismuth (salicylate component), tetracycline-based H. pylori regimens, metoclopramide near term (extrapyramidal symptoms in neonate possible)

— Defer elective H. pylori eradication until postpartum

— Functional dyspepsia in children diagnosed by Rome IV pediatric criteria (≥4 days/month for ≥2 months)

— Workup mirrors adults but with lower threshold for celiac and eosinophilic esophagitis (test before labeling functional)

— First-line: reassurance, dietary modification, treat constipation, CBT

— PPIs and H2 blockers used short-term; avoid metoclopramide

— Strongly consider anxiety/school stress as driver

— Anxiety/depression present in 30–50% of FD patients

— Treat both simultaneously — neither alone fully resolves symptoms

— Choose neuromodulator that addresses both (mirtazapine for depression + early satiety; TCA for anxiety + pain)

— Avoid framing as "it's all in your head" — use gut–brain axis language

Key distinction: In pregnancy, famotidine is the preferred H2 blocker (ranitidine off-market); omeprazole has the most reassuring PPI safety data. Misoprostol is contraindicated.

Board pearl: In an adolescent with chronic dyspepsia and food impaction or atopy history, rule out eosinophilic esophagitis with EGD biopsies before calling it functional.

Pregnancy:

Pediatrics and adolescents:

Comorbid psychiatric disease:

Complications and Adverse Outcomes

— Reduced quality of life equivalent to moderate asthma or heart failure on validated scales

— Lost workdays, healthcare utilization 2–3× higher than non-FD peers

— Increased risk of unnecessary procedures (repeat EGDs, abdominal CTs, cholecystectomies that fail to relieve symptoms)

— Chronic PPI use: C. difficile infection, community-acquired pneumonia, hypomagnesemia (→ tetany, seizures), B12 deficiency, osteoporotic fractures, AIN, possible CKD progression, fundic gland polyps

— Metoclopramide: tardive dyskinesia (irreversible), acute dystonia, akathisia, hyperprolactinemia, depression

— TCAs: anticholinergic toxicity, urinary retention, QT prolongation, weight gain, falls in elderly

— Mirtazapine: weight gain (can be desired), sedation, rare agranulocytosis

— Buspirone: dizziness, serotonin syndrome with MAOIs/SSRIs

— Unnecessary cholecystectomy in functional patients with incidental gallstones — symptoms persist

— EGD complications (perforation 0.03%, bleeding, sedation events)

— Radiation exposure from repeat CTs

— "Diagnostic odyssey" reinforces illness behavior

— Worsening anxiety with normal-test reassurance failure

— Opioid escalation for pain — must be avoided; worsens dysmotility and creates dependence

— Gastric cancer (especially East Asian, immigrant, ≥60 populations)

— Pancreatic adenocarcinoma

— Mesenteric ischemia (postprandial pain in vasculopaths)

— Celiac, EoE, H. pylori, gastroparesis

Step 3 management: At every follow-up, re-screen for alarm features; new weight loss, anemia, or dysphagia must trigger endoscopy even after a prior negative study. The FD label should never close the diagnostic door permanently.

Board pearl: Long-term PPI users should receive annual deprescribing attempts and screening for hypomagnesemia/B12 deficiency. Iatrogenic harm is a board-favorite distractor.

FD itself is not life-threatening, but morbidity is substantial:

Iatrogenic complications from over-treatment:

Procedural complications from over-investigation:

Psychosocial complications:

Missed diagnoses (the true "complication" of mislabeling FD):

When to Escalate Care — Referral and Inpatient Triage

— Failure of two adequate therapeutic trials (PPI + neuromodulator or prokinetic + neuromodulator)

— Persistent symptoms after H. pylori eradication

— Need for EGD that primary care cannot expedite

— Suspected gastroparesis requiring scintigraphy and dietary management

— Suspected EoE, celiac with atypical features, or refractory GERD overlap

— Diagnostic uncertainty after 6 months of management

— Severe symptom burden with documented anxiety/depression

— Patient receptive to CBT or gut-directed hypnotherapy

— Somatization, catastrophizing, or trauma history

— Unintentional weight loss (even mild)

— Restrictive eating, food fears

— Suspected SIBO or post-eradication dysbiosis

— Hematemesis, melena, hemodynamic instability → ED for urgent EGD

— Intractable vomiting with dehydration, electrolyte derangement → admit for IV fluids, antiemetics, and gastric emptying study

— Severe weight loss with nutritional compromise → admit for evaluation and possible enteral support

— Acute severe epigastric pain with new features (radiation, peritoneal signs, fever) → ED to rule out perforated ulcer, pancreatitis, mesenteric ischemia, MI

— Suicidality identified on PHQ-9 → mental health emergency pathway

— Rarely indicated for FD itself

— Indicated only when concurrent surgical pathology identified (e.g., paraesophageal hernia, gastric outlet obstruction)

CCS pearl: If a Step 3 CCS case opens with chronic dyspepsia but the patient develops hematemesis, tachycardia, and hypotension, immediate actions: 2 large-bore IVs, type and cross, IV PPI bolus + drip, IV fluids, consult GI for urgent EGD, NPO, admit to monitored bed. Do not waste a step on outpatient labs.

Board pearl: New onset of any alarm feature in a previously labeled FD patient demands re-evaluation, not dose escalation of current therapy.

GI referral indications (outpatient):

Behavioral health/GI psychology referral:

Nutrition referral:

Inpatient triage — uncommon in pure FD, but escalate when:

Surgical referral:

Key Differentials — Same-Category (Upper GI) Causes

— Gastric ulcer: pain worse with eating; duodenal ulcer: pain 2–3 h post-meal, relieved by food, nocturnal awakening

— Often H. pylori or NSAID-related

— Diagnosed on EGD with biopsy; treat acid + eradicate H. pylori + stop NSAIDs

— Heartburn and regurgitation retrosternal, worse supine, often nocturnal

— Responds well to PPI; alarm features → EGD for Barrett surveillance

— Nausea, vomiting, early satiety, postprandial fullness with objective delayed emptying on 4-h scintigraphy (>10% retention)

— Diabetes (most common cause), post-vagotomy, post-viral, idiopathic

— Manage with dietary modification, prokinetics, glycemic control

— Younger patients, atopic history, dysphagia, food impactions

— Diagnosed on EGD biopsy (≥15 eos/HPF)

— Treat with PPI, topical swallowed steroids (budesonide, fluticasone), elimination diet

— Weight loss, anemia, dysphagia, family history, East Asian origin

— Always endoscopy with biopsy

— Multiple, refractory, or distal duodenal ulcers; diarrhea; high fasting gastrin off PPI

— Rare but classic board item

— Reclassified as "H. pylori–associated dyspepsia" if symptoms resolve durably (>6 months) after eradication; otherwise considered FD

— Stereotyped episodes, hot-shower relief in CHS, chronic cannabis use

Key distinction: FD vs GERD: FD pain/burning is epigastric (between umbilicus and xiphoid); GERD burning is retrosternal with regurgitation. Both may overlap; the dominant symptom location drives initial therapy choice.

Board pearl: FD and gastroparesis exist on a spectrum; scintigraphy distinguishes them, and the distinction matters because prokinetics are first-line in gastroparesis but only subtype-specific in FD (PDS).

Peptic ulcer disease (PUD):

GERD (erosive and non-erosive):

Gastroparesis:

Eosinophilic esophagitis (EoE):

Gastric and esophageal malignancy:

Zollinger-Ellison syndrome (gastrinoma):

H. pylori gastritis without ulcer:

Cyclic vomiting / cannabinoid hyperemesis:

Key Differentials — Non-Upper-GI Causes That Mimic FD

— Symptomatic cholelithiasis: episodic RUQ/epigastric pain, postprandial, fatty food intolerance, lasts 30 min–6 h

— Diagnosed on RUQ ultrasound; treat with cholecystectomy only if symptoms are typical

— Caution: incidental gallstones in an FD patient should not prompt cholecystectomy

— Chronic pancreatitis: epigastric pain radiating to back, steatorrhea, alcohol/smoking history, calcifications on imaging

— Pancreatic adenocarcinoma: weight loss, painless jaundice, new diabetes >50, family history

— Atypical angina/ACS — epigastric burning in women, diabetics, elderly

— ECG and troponin in any high-risk patient with new "indigestion"

— Mesenteric ischemia: postprandial pain (intestinal angina), weight loss from food fear, vasculopathy

— Hypercalcemia, uremia, diabetic ketoacidosis, adrenal insufficiency — all cause epigastric symptoms

— Hepatic congestion (right heart failure) — RUQ/epigastric fullness

— Anterior cutaneous nerve entrapment, rectus sheath hematoma, slipping rib syndrome

— Positive Carnett sign; managed with trigger-point injection

— NSAIDs, bisphosphonates, iron, potassium chloride, doxycycline, GLP-1 agonists, metformin, opioids, SSRIs, cannabis

— Heavy alcohol use

— IBS, chronic idiopathic nausea, somatic symptom disorder, eating disorders (especially restrictive ARFID-pattern)

— Anxiety and depression as both driver and consequence

Key distinction: Postprandial pain + weight loss + vascular risk factors = mesenteric ischemia ("intestinal angina"), not FD. CT angiography is diagnostic; missing this is a board-classic distractor.

Board pearl: In a woman ≥50 with diabetes presenting with new "indigestion," obtain an ECG and troponin first. ACS presents atypically as epigastric burning in this population — a recurrent Step 3 stem.

Biliary disease:

Pancreatic disease:

Cardiac (must not miss):

Renal/hepatic/metabolic:

Abdominal wall pain:

Medications and toxins:

Functional and psychiatric overlap:

Secondary Prevention, Maintenance, and Long-Term Plan

— Small, frequent, low-fat meals (fat delays gastric emptying)

— Avoid late-night eating; finish meals ≥3 h before bed

— Limit caffeine, alcohol, carbonated beverages, spicy/fatty foods if individually triggering

— Smoking cessation — independently improves symptoms; offer nicotine replacement and varenicline

— Weight loss if BMI ≥25 — improves overlapping GERD symptoms

— Regular aerobic exercise — improves gastric accommodation

— Sleep hygiene, stress reduction

— Lowest effective PPI dose with periodic deprescribing trials (step-down to PRN or H2 blocker)

— Avoid chronic NSAIDs; substitute acetaminophen, topical NSAIDs, physical therapy

— Continue H. pylori eradication confirmation testing if treated

— Long-term PPI users: annual magnesium, B12, consider DEXA per usual criteria

— CBT or gut-directed hypnotherapy — durable effect, often outlasts medication

— Mindfulness, yoga — modest but real symptom benefit

— Treat comorbid anxiety/depression to remission, not just response

— Explain gut–brain axis — legitimizes symptoms without organic disease

— Symptom diary linking food, stress, sleep, and symptoms

— Set realistic goals: 50% symptom reduction is a clinically meaningful success

— Avoid doctor-shopping and repeat testing unless alarm features emerge

— Pneumococcal, influenza, COVID per age/risk (especially long-term PPI users at higher CAP risk)

— Colon cancer screening, age-appropriate cancer screening

— Bone health: calcium, vitamin D, weight-bearing exercise

Step 3 management: Construct a written care plan at every visit: target symptom, current therapy, planned reassessment date, deprescribing trigger. This is value-based ambulatory medicine and a Step 3 favorite.

Board pearl: Functional dyspepsia is chronic and relapsing; the goal is durable symptom control, not cure. Setting that expectation upfront reduces frustration and doctor-shopping.

Lifestyle pillars (evidence-based, durable):

Medication stewardship:

Behavioral and gut–brain maintenance:

Patient education and self-management:

Vaccinations and preventive care (don't forget the ambulatory visit):

Follow-Up, Monitoring Parameters, and Counseling

— 4–8 weeks after initiating any new therapy (PPI, prokinetic, neuromodulator) to assess response

— 3 months for stable patients on therapy to evaluate deprescribing

— 6–12 months thereafter, or sooner if symptom change

— Same-day or 1–2 week visit if new alarm feature emerges

— PPI long-term: magnesium, B12, renal function annually; consider DEXA per criteria

— Metoclopramide: monthly screening for abnormal involuntary movements (AIMS scale); stop at first sign of tardive dyskinesia; total duration <12 weeks

— TCAs: baseline ECG if cardiac history or ≥1 QT risk factor; monitor anticholinergic effects, blood pressure, weight

— Mirtazapine: weight, lipids, sedation; rare CBC if signs of infection

— Buspirone: dizziness, drug interactions (CYP3A4)

— Comorbid mental health: repeat PHQ-9 and GAD-7 at each follow-up

— Patient-reported outcome scales (e.g., Nepean Dyspepsia Index, short form)

— Symptom diary with meal/stress correlation

— Validated quality-of-life measures for chronic GI disease

— Reinforce gut–brain framework

— Review medication adherence and timing (PPI 30 min pre-meal is critical)

— Lifestyle reinforcement: weight, exercise, sleep, alcohol, tobacco

— Re-screen alarm features explicitly

— Mental health check-in

— Update preventive care

— Symptom control sustained ≥3 months → attempt PPI step-down (half dose, alternate-day, PRN)

— Neuromodulators: continue 6–12 months after response, then taper slowly over weeks

— Lifestyle changes are permanent

Step 3 management: Build deprescribing into the original plan—at PPI initiation, document the planned reassessment date and step-down strategy. This is patient-centered, value-based care, and frequently rewarded on Step 3 outpatient stems.

Board pearl: Re-screening alarm features at every visit is standard of care; FD is a diagnosis maintained, not just made.

Follow-up cadence:

Monitoring parameters by therapy:

Symptom monitoring tools:

Counseling content at each visit:

When to step down or stop therapy:

Ethical, Legal, and Patient Safety Considerations

— Document discussion of PPI long-term risks (fracture, C. difficile, hypomagnesemia, B12 deficiency, possible CKD progression, AIN) and the rationale for continued use vs deprescribing

— Document metoclopramide tardive dyskinesia risk explicitly; FDA requires patient counseling about irreversible movement disorder; obtain written acknowledgment is recommended in many systems

— TCAs: discuss anticholinergic effects, fall risk in elderly, and the off-label use for FD (informed consent for off-label is standard practice in the US, not legally mandatory but ethically expected)

— Repeat endoscopy without new alarm features is low-value care and ethically questionable — exposes patient to procedural risk and cost

— Defensive medicine vs evidence-based care: document reasoning when declining further testing

— When discharging an FD patient from inpatient observation for alarm symptom workup, ensure explicit handoff to outpatient PCP, with documented test results, pending studies, and follow-up plan

— Medication reconciliation at every transition; PPIs started inpatient often inappropriately continued indefinitely outpatient ("PPI legacy prescribing") — actively review and deprescribe

— Suicidality identified on PHQ-9 → emergency mental health pathway, safety planning, lethal means counseling

— Suspected eating disorder with restrictive eating masquerading as FD → adolescent protective considerations

— Elder abuse if weight loss is from neglect rather than disease — mandatory reporting in all US states

— Gastric cancer incidence is higher in immigrants from East Asia, Latin America, Eastern Europe — adjust endoscopy threshold accordingly, regardless of age

— Cost of long-term PPI vs generic H2 blocker — discuss with uninsured patients

— Rome IV criteria explicitly noted

— Alarm features reviewed and absent

— Subtype identified, therapy rationale

— Shared decision-making

Board pearl: "PPI legacy prescribing" at hospital discharge is a classic transition-of-care safety failure—every outpatient visit should reconcile and consider deprescribing. Step 3 rewards this active stewardship.

Informed consent for long-term therapy:

Avoiding diagnostic over-testing:

Transitions of care risks (a Step 3 favorite):

Mandatory reporting and safety:

Health equity considerations:

Documentation essentials:

High-Yield Associations and Rapid-Fire Clinical Facts

Board pearl: Memorize the subtype-to-drug map — it's the single most common Step 3 FD question structure.

Key distinction: FD = symptoms without structural disease + Rome IV; gastroparesis = symptoms + objective delayed emptying.

Rome IV requires symptoms ≥3 months with onset ≥6 months prior — memorize the timing.

FD subtypes: PDS (postprandial distress) vs EPS (epigastric pain) — drives drug choice.

Test-and-treat H. pylori is first-line in <60, no alarms; urea breath or stool antigen, not serology.

Hold PPIs ≥2 weeks and antibiotics/bismuth ≥4 weeks before H. pylori testing.

Bismuth quadruple therapy ×14 days is preferred first-line eradication in the US (clarithromycin resistance >15%).

Endoscopy threshold: age ≥60 with new dyspepsia, or any alarm feature at any age.

Alarm features (VBAD-W): Vomiting, Bleeding/anemia, Age ≥60, Dysphagia/weight loss, Worsening/nocturnal.

EPS → PPI/TCA; PDS → prokinetic/buspirone/mirtazapine.

SSRIs do NOT improve FD-specific symptoms — choose TCAs, buspirone, or mirtazapine.

Metoclopramide ≤12 weeks — black-box tardive dyskinesia.

Buspirone improves gastric accommodation — PDS subtype.

Mirtazapine ideal for early satiety + weight loss + anxiety/insomnia.

Amitriptyline avoided in elderly (Beers); nortriptyline preferred.

Positive Carnett sign → abdominal wall pain, not FD.

CBT and gut-directed hypnotherapy = effect size comparable to medications.

Pregnancy ladder: antacids → sucralfate → famotidine → omeprazole; avoid misoprostol.

Long-term PPI risks: C. diff, CAP, hypomagnesemia, B12 deficiency, fractures, AIN.

Gastroparesis requires >10% retention at 4 hours on solid-phase scintigraphy.

Mesenteric ischemia = postprandial pain + weight loss + vasculopathy — get CTA.

Atypical ACS presents as epigastric burning in women, diabetics, elderly — ECG and troponin.

Post-infectious FD is a recognized subtype after gastroenteritis.

Celiac serology and H. pylori testing are part of standard initial outpatient workup.

Eosinophilic esophagitis (≥15 eos/HPF) — always biopsy at EGD in younger atopic patients.

Iron-deficiency anemia in dyspepsia = alarm; always endoscope.

Board Question Stem Patterns

— 35-year-old with 4 months of epigastric burning, no alarms, normal labs. Best next step? → H. pylori urea breath test or stool antigen. Distractors: empiric PPI (acceptable but not best first), endoscopy (not indicated), serology (wrong test).

— 62-year-old with 3 months of new postprandial fullness, no other features. Best next step? → Upper endoscopy. Age ≥60 mandates EGD regardless of alarms.

— Patient with predominant postprandial fullness and early satiety, H. pylori negative, failed PPI. Next? → Buspirone or mirtazapine (PDS), not another PPI.

— Patient on metoclopramide 6 months develops lip-smacking movements. Next step? → Stop metoclopramide immediately; tardive dyskinesia is often irreversible.

— 58-year-old diabetic woman with new "indigestion" and diaphoresis. Next step? → ECG and troponin. Do not start PPI.

— Vasculopath with postprandial pain and weight loss → CT angiography of mesenteric vessels.

— Pregnant patient with dyspepsia not relieved by antacids → sucralfate, then famotidine, then omeprazole. Avoid misoprostol.

— Stable FD patient on PPI 2 years → attempt step-down to lowest effective dose or PRN, monitor B12/magnesium.

— Epigastric pain worse with abdominal wall tensing → trigger-point injection, not endoscopy.

— Microcytic anemia + dyspepsia → upper endoscopy (and colonoscopy if age-appropriate).

— Young atopic patient with dyspepsia and intermittent dysphagia → EGD with biopsies, look for ≥15 eos/HPF.

— Patient discharged on new PPI from hospital — at PCP visit, reconcile and consider deprescribing.

Board pearl: When the stem includes any alarm feature (weight loss, anemia, dysphagia, hematemesis, age ≥60), the answer is almost always endoscopy, not empiric therapy.

Pattern 1 — Classic test-and-treat:

Pattern 2 — Age-based endoscopy trigger:

Pattern 3 — Subtype-directed therapy:

Pattern 4 — Metoclopramide safety:

Pattern 5 — Atypical ACS mimic:

Pattern 6 — Mesenteric ischemia:

Pattern 7 — Pregnancy ladder:

Pattern 8 — PPI deprescribing:

Pattern 9 — Carnett sign:

Pattern 10 — Iron-deficiency anemia in dyspepsia:

Pattern 11 — Eosinophilic esophagitis:

Pattern 12 — Transition of care:

One-Line Recap

Functional dyspepsia is a Rome IV clinical diagnosis (≥3 months of postprandial fullness, early satiation, epigastric pain, or burning, without structural disease) managed in the outpatient setting by excluding alarm features, treating H. pylori test-and-treat in patients under 60, and applying subtype-directed therapy—PPI/TCA for epigastric pain syndrome and prokinetic/buspirone/mirtazapine for postprandial distress syndrome—alongside lifestyle modification and gut–brain behavioral therapy.

Board pearl: The single highest-yield Step 3 move is matching subtype to drug while never missing an alarm feature—FD is a diagnosis maintained, not just made.

Recap 1 — Diagnosis: Rome IV criteria + absence of alarm features (vomiting, bleeding/anemia, age ≥60, dysphagia/weight loss, worsening/nocturnal); endoscopy mandatory if age ≥60 or any alarm.

Recap 2 — Initial workup: CBC, CMP, TSH, celiac serology, pregnancy test; non-invasive H. pylori (breath/stool antigen, not serology) with PPI held ≥2 weeks; ECG if cardiac risk; RUQ ultrasound only if biliary pattern.

Recap 3 — Therapy by subtype: EPS → PPI 4–8 weeks then TCA (nortriptyline preferred in elderly); PDS → prokinetic (metoclopramide ≤12 weeks, black-box TD), buspirone for accommodation, or mirtazapine for early satiety/weight loss/anxiety; SSRIs do not improve FD symptoms; CBT and gut-directed hypnotherapy have effect sizes comparable to drugs.

Recap 4 — Longitudinal care: Re-screen alarms at every visit, deprescribe PPI annually with magnesium/B12 monitoring, reconcile medications at every transition, treat comorbid anxiety/depression, and frame the disorder through the gut–brain axis to set durable expectations.