FUNCTIONAL DYSPEPSIA
Manoon M.
3/9/20
Update management for general practice
Outline
• Dyspepsia
• Uninvestigated dyspepsia (UD)
• Functional dyspepsia (FD)
• Alarm symptoms
• Esophagogastroscopy (EGD)
• Treatment for FD
DYSPEPSIA
•A heterogeneous group of symptoms (pain or discomfort) in the upper abdomen without alarm symptoms for at least 4 weeks.
Thailand Dyspepsia Guidelines 2018
Dyspeptic symptoms
Epigastric pain or burning Belching*
Sensation of fullness Nausea and vomiting
Early satiation Upper abdominal bloating
Anorexia Heartburn and regurgitation
* the most common manifestation in Asian countries
Thailand Dyspepsia Guidelines 2018
Organic causes of dyspepsia LUMINAL GI TRACT PANCREATICOBILIARY DISORDERS
• Chronic gastric volvulus • Chronic gastric or intestinal ischemia • Food intolerance • Gastric infections (CMV, fungus, tuberculosis,
syphilis) • Gastric or esophageal neoplasms • Gastroesophageal reflux disease • Gastroparesis (diabetes mellitus, postvagotomy,
scleroderma, chronic intestinal pseudo-obstruction, postviral, idiopathic)
• Irritable bowel syndrome • Infiltrative gastric disorders (Ménétrier disease,
Crohn disease, eosinophilic gastroenteritis, sarcoidosis, amyloidosis)
• Parasites (Giardia lamblia, Strongyloides stercoralisrom)
• Peptic ulcer disease
• Biliary pain: cholelithiasis, choledocholithiasis, SOD
• Chronic pancreatitis • Pancreatic neoplasms
SYSTEMIC CONDITIONS
• Adrenal insufficiency • Diabetes mellitus • Heart failure • Hyperparathyroidism • Intra-abdominal malignancy • Myocardial ischemia • Pregnancy • Renal insufficiency • Thyroid disease
Sleisenger and Fordtran’s 11th ed,2021
MEDICATIONS
• Acarbose • Alcohol • Antibiotics, oral (e.g., erythromycin, penicillin,
macrolides) • Aspirin, NSAIDs (including COX-2 selective agents) • Bisphosphonates • CCBs • Colchicine • Corticosteroids • Digitalis preparations • Estrogens • Herbs (e.g., garlic, ginkgo, saw palmetto, feverfew,
chaste tree berry, white willow)
• Iron • Potassium chloride • Levodopa • Metformin • Narcotics • Niacin • Gemfibrozil • Nitrates • Opiates • Orlistat • Quinidine • Sildenafil • Theophylline
Adapted from Loyd RA & McClellan DA .Am Fam Physician 2011 Mar 1;83(5):547-52 Talley NJ, Ford AC. N EnglJ Med 2015;373:1853-63
Sleisenger and Fordtran’s 11th ed,2021
Dyspepsia ควรสงตรวจเพมเตม เมอไหร? ไมเคยเปนมากอน - อาการเขาไดกบdyspepsia? สาเหตทซกประวตพบ? มตวตาเหลอง? มความเสยงโรคหวใจขาดเลอด? ถาไมชดเจนควรตรวจเพมเตม
เคยเปนมากอน รกษาแลวดขน - อาการเหมอนเดม? สาเหตเหมอนเดม? มการใชยาตวใหมๆ/อาหาร/เครองดมทอาจเปนสาเหต? มalarm symptomsไหม?
รกษาแลวไมดขน - เหมอนกลมเคยรกษาแลวดขน และ ประเมนวาใหยาขนาดเหมาะสมแลวหรอไม ใหมานานแคไหนแลว เคยสงตรวจทางหองปฏบตการ/อลตราซาวดชองทองบางหรอไม
UNINVESTIGATED DYSPEPSIA (UD)
• Dyspeptic symptoms in people who have not yet undergone specific diagnostic investigations.
Thailand Dyspepsia Guidelines 2018
FUNCTIONAL DYSPEPSIA (FD)
• Dyspeptic symptoms cannot be explained by a routine clinical evaluation, including endoscopy, and there is no evidence of Helicobacter pylori infection.
• 2 subcategories:
(1) Postprandial distress syndrome
Postprandial fullness and early satiation (related to meal).
(2) Epigastric pain syndrome
Epigastric pain and epigastric burning (not related to meals).
Thailand Dyspepsia Guidelines 2018
FUNCTIONAL DYSPEPSIA (FD)
• The worldwide prevalence of UD varies from 7% to 34%, with a pooled UD prevalence from 21 Southeast Asian studies of 21.6%.
• In Asian populations, the risk of malignancy associated with UD is approximately 1.3% (95% CI, 0.80-2.10).
• Secondary dyspepsia was identified in 18% of UD patients after undergoing an endoscopy in Asian countries.
• In Thailand, 60-90% of patients with dyspepsia are eventually diagnosed with FD
• FD is a benign but chronic condition that often fluctuates and is sometimes recurrent.
Thailand Dyspepsia Guidelines 2018
ALARM FEATURES
• Evidence of upper GI bleeding hematemesis, melena, maroon stool, or iron deficiency without other causes.
• Early satiety.
• Unexplained weight loss (>10% body weight).
• Persistent vomiting due to an unknown cause (defined as vomiting > 10 times in 24 hours or vomiting after each meal).
• Family history of upper GI cancer in a first-degree relative.
Thailand Dyspepsia Guidelines 2018
ESOPHAGOGASTRODUODENOSCOPY (EGD)
• Dyspeptic patients who have 1 of the following: (1) Age of onset of 50 years or older (2) Alarm features (3) Symptoms are non-responsive to a trial of appropriate medical therapy.
Thailand Dyspepsia Guidelines 2018
GERD Dyspepsia
(Duration ≥ 4 weeks)
Uninvestigated Investigated
Organic
18%
PUD 11%
Erosive esophagitis 6%
Malignancy 1%
Functional
60-90%
Postprandial distress
syndrome
Epigastric pain syndrome
Alarm symptoms
1) UGIB
2) Early satiety
3) Weight loss (>10%)
4) Vomiting > 10 times in 24 hours or vomiting after each meal
5) Family history of upper GI cancer in a first-degree relative
IBS
Thailand Dyspepsia Guidelines 2018 StanghelliniV., et al. Gastroenterology. 2016 May;150(6):1380-92
Rome IV Criteria for Functional Dyspepsia • Presence of 1 symptom(s) of postprandial fullness, early satiety, epigastric pain, or epigastric burning • No evidence of structural disease that could explain the symptoms
PDS (38%) Postprandial fullness or early satiety 3 days/week for the past 3 months and onset 6 months before diagnosis
EPS (27%) Epigastric pain and/or burning 1 day(s)/week for the past 3 months and onset 6 months before diagnosis
Overlap PDS/EPS 35% Drossman DA, Hasler WL. Gastroenterology. 2016;150(6):1257-1261.
Talley NJ. Korean J Intern Med 2016
Etiology of Functional Dyspepsia
TREATMENT OF FUNCTIONAL DYSPEPSIA
Treatment modalities
• Pharmacotherapy • Acid-Reducing Therapy • Neuromodulators • Prokinetics and Fundus-Relaxing Therapies
• Complementary and Alternative Medicine
• Psychological Therapies
• Helicobacter pylori Eradication
Kimberly N. Harer, et al. Gastroenterology & Hepatology Volume 16, Issue 2 February 2020
Pharmacotherapy Treatment Therapeutic efficacy Quality of
evidence
PPIs Therapeutic gain 7-10% NNT 10-13 Mod
H2RA Therapeutic gain 8-35% NNT 7-13 Low/mod
Prokinetics Therapeutic gain 18-45% NNT 6-7 Low
TCAs, antipsychotics Response rates 64-70% NNT 6 NNH 21
Low
Rebamipide Better than placebo SMD -0.62 Low
SSRI/SNRI = Placebo NNH 6-16 Very low
Antacid, bismuth, sucralfate
= Placebo NA Very low
Lacy BE, et al. Aliment Pharmacol Ther 2012;36:3-15 Ford AC, et al. Gut 2017;66:411-20 Jaafar MH, et al. Dig Dis Sci 2018;63:1250-60
Pinto-Sanchez MI, et al. Cochrane Database Syst Rev 2008 Pittayanon R, et al. Am J Gastroenterol 2018;114:233-243
Moayyedi PM, et al. ACG Guideline 2017
Neuromodulators
• Sulpiride
• Levosulpiride
• Mirtazapine
• Tricyclic antidepressants (TCAs) • Amitriptyline and imipramine
*** Not nortriptyline, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNSIs).
Ford AC, et al. Gut 2017;66:411-420 Kimberly N. Harer, et al. Gastroenterology & Hepatology Volume 16, Issue 2 February 2020
Serotonin Receptor agonist
Pro-kinetic Drug
D2 Receptor antagonist
- Metoclopramide* - Cisapride - Mosapride
- Domperidone - Itopride
* Metoclopramide: action both serotonin agonist and D2 antagonist
Prokinetic agents in Thailand Metoclopramide (Plasil)
Domperidone (Motilium)
Itopride (Ganaton)
Mosapride (Gasmotin)
Mode of action D2 antagonist (5HT4 agonist ) (5HT3 antagonist)
D2 antagonist
D2 antagonist AChE inhibitor
5HT4 agonist
Metabolism pathway CYP450 CYP450 FMO3 CYP450
Prokinetic effects Strong Moderate Strong Strong
Antiemetic effects Strong Moderate-strong Moderate None
QT prolong - + - A case report
Prolactin elevation Rare-moderate Rare-moderate Rare Rare
EPS effects Frequent Rare Rare Rare
Organ selectivity Upper gut Upper gut Upper gut (lower?) Upper and lower gut
ใหยาอยางไร? เมอไหร? เรยกวาตอบสนองหรอไมไดผล
Thailand Dyspepsia Guidelines 2018
ใหยาอยางไร? เมอไหร? เรยกวาตอบสนองหรอไมไดผล
Thailand Dyspepsia Guidelines 2018
Omeprazole 20-40mg/day 4-8 weeks
Domperidone 10mg tid or qid ac Mosapride 5mg tid ac
Amitriptyline 25-50 mg/day
Rebamipide 100mg tid ac
Refractory functional dyspepsia
• FD that has continuous symptoms for at least 8 weeks and has been unresponsive to at least 2 medical treatments.*
• The guidelines for FD in the Asia-Pacific region and the United States of America (USA) recommend changing to a different drug if adequate therapeutic efficacy has not been achieved after 4 weeks of treatment.
* Miwa H. et al. J Gastroenterol 2015;50:125-139.
Management of Refractory FD
• H2-RA if PPIs have failed.
• Combination of acid suppression with a prokinetic agent.
• Combination of drug therapy with psychological treatment.
• Adjusting the dose of a TCA, prescribing an antipsychotic drug such as levosulpiride, or adding an anxiolytic.
• The combination of an antidepressant with pregabalin or gabapentin is yet another option that appears to relieve pain.
• Opioids have no therapeutic role and should be avoided because of the risk of dependence.
Neurogastroenterol Motil 2015; 27: 455-67 Am J Gastroenterol 2014; 2: 22-30
หยดยาไดไหม?
Thailand Dyspepsia Guidelines 2018
หยดยาไดไหม?
ถาอาการดขน คอยๆลดยาลง เชน จาก Multiple drugs single drug
BID dose OD dose วนเวน1-2วน เฉพาะเวลามอาการ
ภายใน 6-12 เดอน
Thailand Dyspepsia Guidelines 2018
โรคนจะหายไหม?
• All FD patients should be offered a positive diagnosis after targeted investigation
• Attention to stress reduction and lowering of anxiety is important
50% Resolution of symptoms
30-35% Symptoms fluctuate and/or meet criteria for another FGIDs
15-20% Persistent symptoms
No evidence to suggest that it is associated with decreased survival
Talley NJ, Ford AC. N Engl J Med 2015;373:1853-63
อย รพช. เมอไหร? ควรสงตอพบแพทยเฉพาะทาง
Thailand Dyspepsia Guidelines 2018
อย รพช. ควรสงตอพบแพทยเฉพาะทางเมอไหร?
Thailand Dyspepsia Guidelines 2018
หาม/แนะน าการรบประทานอาหาร,เครองดมอยางไรบาง?
Dietary recommendations for patients with functional dyspepsia.
• Eat slowly and regularly.
• Decrease fat intake.
• Try to observe a diet that is more similar to a Mediterranean diet or increase
the intake of fresh foods and decrease the intake of ultra-processed foods.
• Decrease coffee and alcohol consumption.
• A gluten-free diet and a low-FODMAPs diet could be tested over a short time
period (4–8 weeks) and must be stopped if there is no efficacy.
• Be careful in providing strong recommendations to obsessive patients, and
avoid the recommendation of very restrictive diets.
Duboc et al. Front. Psychiatry, 05 February 2020
หาม/แนะน าการรบประทานอาหาร,เครองดมอยางไรบาง?
Dietary recommendations for patients with functional dyspepsia.
• Eat slowly and regularly.
• Decrease fat intake.
• Try to observe a diet that is more similar to a Mediterranean diet or increase
the intake of fresh foods and decrease the intake of ultra-processed foods.
• Decrease coffee and alcohol consumption.
• A gluten-free diet and a low-FODMAPs diet could be tested over a short time
period (4–8 weeks) and must be stopped if there is no efficacy.
• Be careful in providing strong recommendations to obsessive patients, and
avoid the recommendation of very restrictive diets.
Duboc et al. Front. Psychiatry, 05 February 2020
รบประทานชาๆ เนอสตวไมผานการปรงแตง เนนผกผลไม ไมมน ไมหวาน ไมหมกดอง งดกาแฟและแอลกอฮอล
สมนไพร/อาหารเสรม ทชวยใหดขนมไหม?
• Peppermint
• Ginger (ขง)
• STW5
• FDgard
• Turmeric (ขมนชน)
THANK YOU
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