functional dyspepsia

New Engl J  Med just had a useful review of the remarkably common "functional dyspepsia" (see functional dyspepsia NEJM2015 in dropbox, or N Engl J Med 2015;373:1853-63​)​. their points:

--Definition: Rome III criteria -- sensation of pain or burning in epigastrium, early satiety, fullness during or after a meal, or a combo of these symptoms; lasting at least 6 months and occurring at least weekly, and no organic explanation

--but, symptoms above to not reliably distinguish "functional" from organic cause: <10% with dyspepsia have a peptic ulcer, <1% gastroesophageal cancer, and >70% have functional dyspepsia as determined by EGD (ie, nothing found)

--one other overlapping diagnosis is GERD, but more than 50% of patients meeting functional dyspepsia criteria with symptoms of heartburn and regurgitation had normal 48-hour pH studies, and in these patients, heartburn/regurgitation was the predominant functional dyspepsia symptom in 30%

--there is obvious overlap also with gastroparesis.  more than 25% of patients with functional dyspepsia have evidence of delayed gastric emptying, and up to 86% of those with gastroparesis meet Rome III criteria for functional dyspepsia

--even looking at "alarm symptoms" (>55 yo with new-onset dyspepsia, dysphagia, vomiting, weight loss, family hx of gastric/esophageal cancer, Fe-deficiency anemia), still had low probability of finding cancer (0.8% in a large meta-analysis -- Gastroenterology 2006; 131: 390)

--frequency of celiac disease, the great imitator, is not increased in those with dyspepsia

--in terms of routine testing: they recommend H pylori stool antigen or breath test when the prevalence of H pylori infection is at least 10%, or, if you don't know prevalence, it is still reasonable

--there is a trend to distinguish 2 types of functional dyspepsia, with the hope that there may be different effective therapies:

    --epigastric pain syndrome: intermittent pain or burning in the epigastrium occurring at least 1x/week

    ​--postprandial distress syndrome:  bothersome postprandial fullness after normal-sized meals or early satiety preventing finishing a regular meal, several times/wk

--etiology of functional dyspepsia: there is a pretty clear relationship between anxiety/psychological distress and functional dyspepsia (though occasionally there is dyspepsia before onset of anxiety, leading some authors to posit a bidirectional "brain-gut pathway", and some studies suggest a disorder in central pain processing), and there may be genetic factors. some patients have evident disturbances of gastric physiology (eg slow gastric emptying, etc), but some have none of these abnormalities. also some question of infectious etiology (though Koch's postulates have not been fulfilled for any microbe).  but contenders are salmonella, e coli 0157, campylobacter jejuni, giardia, norovirus (these can all induce functional dyspepsia symptoms). duodenal inflammation is found in 40%, esp with eosinophilia (which can be related to smoking).  H Pylori may also be associated, and a small % of patients do better after eradication of infection. food intolerance/allergy could be involved, but this is not adequately studied. one of the new models is: in genetically-predisposed people, an allergen or infection leads to immune activation, recruitment of eosinophils (which may be protective/promote healing, but can also lead to tissue injury and symptoms perhaps because an inflamed duodenum may be more sensitive to acid. of interest there are preliminary data in kids that montelukast reduces symptoms) [though only 40% have duodenal inflammation, so not the whole story]

--treatment

    --30-40% respond to placebo (although not studied in functional dyspepsia, placebo works better than no treatment in those with irritable bowel -- ie, it is a true placebo effect)

    ​--H Pylori eradication: large meta-analysis suggested that 90% have persistent symptoms after eradication, with NNT of 15 (though this was still significant)

    --PPIs have relative risk of persistent symptoms of 87% with NNT of 10

    --H2-blockers may be better than PPIs, with relative risk of persistent symptoms of 77% with NNT of 7 (though lower quality of trials)

    --prokinetic agents: most are too dangerous. there is a new one in Japan called acotiamide (an acetylcholinesterase inhibitor), with initial trials showing improvement in 52% (vs 35% placebo), ongoing trials in US and the West

     --buspirone: randomized cross-over trial in 17 patients showed it was effective in relaxing the gastric fundus, decreasing bloating and postprandial fullness.

    ​--antidepressants: some data that amitriptyline works better than escitalopram or placebo. other studies do not find efficacy for venlafaxine or sertraline. mirtazapine may help in those with weight loss

    --psychological therapy: under-studied, but some data for improved quality of life and symptom score at 10 weeks which persisted after the end of treatment

    ​--complementary/alternative meds: not much data, though some patients seem to benefit from capsaicin or STW5, a nine-herb comination product also called iberogast

so, overall approach:

--stress reduction, if possible

--dietary advice: small, regular, low-fat meals and avoiding those that precipitate symptoms

--if alarm symptoms, get upper endoscopy (EGD)-- though low yield

--if H  Pylori prevalence is >10%, get stool antigen and treat if positive

--consider empirical acid suppression for 4-8 weeks. if works, try drug holiday after 3 months. may be better to try H2-blocker first

--consider tricyclic antidepressant for 3 months. if works, consider drug holiday

--consider prokinetic agent (esp acotiamide, if you live in Japan)

--avoid opiates. can consider combo therapies (eg, some data that acid suppression and prokinetic agent combo works better). also ?buspirone