Serotonergic signaling in gastric physiology and motility disorders.

In adults with chronic nausea and/or vomiting (defined as symptoms that persist more than 4 weeks), whether nausea or vomiting occurs alone or together, and including patients in whom early satiety, postprandial fullness or bloating dominate the clinical picture rather than nausea and vomiting themselves (Statement 17), first exclude pharmacological causes: current medications should be reviewed (Statement 4, moderate evidence, 94% agreement). Endocrine and metabolic causes should be excluded (Statement 1, low evidence, 94% agreement) with bloods comprising thyroid assessment (TSH and T4), glucose, creatinine, calcium and phosphate, parathyroid hormone, and blood urea nitrogen. Pregnancy is identified as the commonest endocrinologic cause and must be considered in any woman of childbearing age. Upper endoscopy is NOT positioned by this guideline as a universally mandatory first test; rather, absence of abnormalities at upper endoscopy is a required element of the diagnosis of chronic unexplained nausea (Statement 74), and oesophagogastroduodenoscopy is the recommended starting point specifically where an oesophageal motility disorder is suspected. Oesophageal manometry is recommended ONLY if oesophageal symptoms are present (Statement 15). Where initial investigation for structural, toxic and metabolic disorders is negative, assess for digestive motility and gut-brain interaction disorders. A gastric emptying test is necessary to establish a diagnosis of gastroparesis in patients with unexplained chronic nausea and vomiting (Statement 19, moderate evidence, 91% agreement); acceptable methods are scintigraphy and octanoic acid breath test (Statement 20, moderate evidence, 94% agreement), with an accurate 4-hour measurement and, at best, absence of medications that impact gastric motility (e.g., prokinetics or opioids). For gastroparesis treatment specifically, defer to the AGA 2025 guideline (supporting source): metoclopramide (conditional, low certainty; counsel on the tardive dyskinesia black-box warning) or erythromycin (conditional, very low certainty; tachyphylaxis managed with drug holidays) for initial pharmacologic treatment; conditional recommendations AGAINST first-line use of domperidone, prucalopride, aprepitant, nortriptyline, buspirone, and cannabidiol; conditional recommendations against routine initial use of botulinum toxin injection, G-POEM, and gastric electrical stimulation, reserving the latter for select patients refractory to medical therapy (G-POEM studied in patients with ≥6-12 months of moderate symptoms and ≥20% gastric retention at 4 hours). The AGA panel explicitly notes that a conditional recommendation against an agent does not preclude its use for an individual patient after shared decision-making weighing benefits and harms; no recommendation was issued on surgical pyloric interventions (evidence gap).