Functional Vomiting

Functional vomiting is recurrent vomiting, occurring on average at least once per week over the last 3 months, with onset at least 6 months before diagnosis. It is diagnosed in the absence of self-induced vomiting, an eating disorder, rumination, a major psychiatric disorder, or organic, systemic or metabolic disease that explains the vomiting. There must also be no diagnosis of cyclic vomiting syndrome or cannabinoid hyperemesis syndrome.

• It is uncommon, with a prevalence of about 1 to 2% of adults, and about 1% of the population in surveys. Women are affected somewhat more than men, and it occurs in young and middle aged adults. It is often under recognised, and may be misdiagnosed as gastroparesis.
• Mechanisms (not fully defined): abnormalities of the brain gut axis, visceral hypersensitivity, altered gastric motor function (impaired accommodation, delayed emptying, and gastric dysrhythmia in some), autonomic dysfunction, psychological factors (anxiety, depression, trauma, and stress), and conditioned responses.
• Associations: functional dyspepsia, functional nausea, irritable bowel syndrome, migraine, anxiety, depression, chronic pain, and use of cannabis or opioids. Vomiting may follow a stressful event, or a viral gastroenteritis (post-infectious).
• Difference from cyclic vomiting syndrome: functional vomiting has frequent but unpredictable episodes (at least once per week), with no stereotypical pattern. Cyclic vomiting syndrome causes intense, stereotypical episodes of acute vomiting lasting hours to days, separated by symptom free intervals of weeks to months.
• Difference from rumination: rumination syndrome involves effortless regurgitation of recently ingested food within minutes of a meal without nausea, whereas functional vomiting is true vomiting (with nausea, retching and forceful expulsion).
• Complications: dehydration, electrolyte disturbance (hypokalaemia, hypochloraemic metabolic alkalosis), weight loss and malnutrition, dental erosion, oesophagitis, Mallory-Weiss tears, aspiration, reduced quality of life, and work absence.

• Recurrent episodes of nausea, retching and vomiting, which may occur daily or several times per week, unrelated to meals or related to meals in some patients, and with variable severity. Vomitus is food or fluid, occasionally bilious. Patients often feel nauseated before vomiting and some report relief afterwards.
• Associated features: abdominal discomfort, bloating, early satiety, anxiety, fatigue, and sleep disturbance. Weight loss is uncommon, unless vomiting is severe.
• Examination: normal general appearance, normal weight, mild epigastric tenderness, and no signs of dehydration (unless acute vomiting). Dental erosion (suggesting chronic acid exposure), calluses on the knuckles (Russell sign) in self-induced vomiting, and parotid enlargement suggest bulimia or purging and are not features of functional vomiting.
• Differential diagnosis:
  • Gastrointestinal obstruction (gastric outlet obstruction, small bowel obstruction, superior mesenteric artery syndrome, malrotation), gastroparesis, intestinal pseudo obstruction, peptic ulcer disease, gastritis, coeliac disease, pancreatitis, biliary disease, hepatitis, inflammatory bowel disease, and chronic mesenteric ischaemia.
  • Cyclic vomiting syndrome, cannabinoid hyperemesis syndrome (chronic cannabis use, with relief from hot showers or baths), rumination syndrome, and eating disorders (bulimia nervosa, purging).
  • Medicines and toxins: opioids, chemotherapy, digoxin, theophylline, antibiotics, SSRIs, metformin, GLP-1 receptor agonists, oral contraceptives, alcohol, and heavy metals.
  • Metabolic and endocrine: pregnancy, diabetic ketoacidosis, hypercalcaemia, adrenal insufficiency, thyroid disease, uraemia, and porphyria.
  • Neurological: raised intracranial pressure, brain tumour, migraine, vestibular disease, and Chiari malformation.
  • Psychological: anxiety, depression, psychogenic vomiting and somatic symptom disorder.
• Red flags:
  • haematemesis or melaena
  • weight loss
  • severe or persistent abdominal pain or distension
  • early morning vomiting with headache
  • neurological signs or visual disturbance
  • bilious or faeculent vomiting
  • jaundice
  • a succussion splash
  • fever
  • nocturnal vomiting
  • dysphagia
  • anaemia
  • a family history of gastrointestinal cancer
  • age over 50 years with new vomiting

• A diagnosis of exclusion, made after a careful history (frequency, timing, relation to meals, character of vomitus, relief of symptoms, cannabis and substance use, medicines, hot bathing behaviour, body image and eating, weight history, and psychological stressors) and examination.
• Initial tests: full blood count, urea, electrolytes, bicarbonate, calcium, glucose or HbA1c, liver function tests, amylase or lipase, thyroid function tests, C-reactive protein, urinalysis, urine pregnancy test, coeliac serology (tissue transglutaminase IgA with total IgA), and a urine toxicology screen if substances are suspected.
• Upper endoscopy (with biopsies for Helicobacter pylori and duodenal biopsies) to exclude mechanical obstruction, ulcer disease, malignancy, and mucosal disease. Test for Helicobacter pylori.
• Imaging: abdominal ultrasound, CT or MR enterography, or a small bowel follow through to exclude obstruction and structural disease, and CT angiography for suspected mesenteric ischaemia.
• Gastric emptying scintigraphy (4 hour solid meal), antroduodenal manometry, or wireless motility capsule for suspected gastroparesis or pseudo obstruction. Perform them off prokinetic, opioid, and anticholinergic medicines. Vomiting with normal gastric emptying and normal imaging supports a functional disorder.
• Brain imaging (MRI) and neurological assessment for neurological signs, headache, or early morning vomiting.
• Screen for eating disorders, anxiety, depression, trauma, and cannabis use, with careful and non-judgemental questions.
• Assess nutrition (weight, body mass index, albumin, vitamins, and minerals), hydration, and electrolytes.

• A positive diagnosis with an explanation of the condition and a treatment plan. Avoid repeated invasive tests, and agree on a single coordinating clinician.
• Acute vomiting with dehydration:
  • Intravenous fluids: 0.9% sodium chloride or Ringer lactate 1 to 2 L over 2 to 4 hours, with 20 to 40 mmol of potassium chloride per litre once urine output is established, and glucose 5% with sodium chloride when fasting for more than 24 hours.
  • Antiemetic therapy: ondansetron 4 to 8 mg IV or orally, or metoclopramide 10 mg IV, or prochlorperazine 12.5 mg intramuscularly.
  • Thiamine 100 mg IV or orally daily for patients with prolonged vomiting or weight loss, and correction of electrolytes.
  • Admit for severe dehydration, electrolyte disturbance, or inability to maintain oral intake.
• Diet and lifestyle: small frequent meals, low fat and low fibre foods, liquid meals or soups when vomiting is frequent, adequate fluids, avoiding trigger foods and strong smells, and stopping alcohol, cannabis and tobacco. Treat sleep disturbance, stress and anxiety.
• Drug treatment for chronic vomiting (a 4 to 8 week course, with review):
  • Antiemetics:
    • Ondansetron 4 to 8 mg orally (or sublingually) 8 to 12 hourly, with constipation, headache and QT prolongation.
    • Promethazine 12.5 to 25 mg orally 8 hourly, prochlorperazine 5 to 10 mg orally 8 hourly, or metoclopramide 5 to 10 mg orally 3 times daily before meals, for no more than 5 days at a time.
    • Domperidone 10 mg orally 3 times daily before meals (shortest time, check QT interval).
  • Neuromodulators (the main option for refractory symptoms):
    • Mirtazapine 7.5 mg orally at night, increased to 15 to 30 mg after 1 to 2 weeks, with a benefit in many patients and weight gain and sedation as adverse effects.
    • Amitriptyline 10 mg at night, increased by 10 mg every 1 to 2 weeks to 25 to 50 mg (avoid when gastroparesis is documented, because of slowing of gastric emptying).
    • Nortriptyline 10 to 25 mg at night is an alternative.
    • Buspirone 5 to 10 mg orally 3 times daily for impaired gastric accommodation.
  • Aprepitant 125 mg orally on day 1, then 80 mg once daily for refractory vomiting in specialist care.
  • Treat reflux, Helicobacter pylori, and migraine when present (propranolol 40 to 80 mg twice daily or amitriptyline for migraine prophylaxis).
  • Avoid opioids, benzodiazepines, and cannabis.
• Psychological treatment: cognitive behavioural therapy, gut directed hypnotherapy, relaxation, and stress management, which are important for the many patients with anxiety or depression or who have trauma.
• Nutritional support: dietitian review, oral nutritional supplements, and enteral feeding with a nasojejunal tube or jejunostomy in severe cases with weight loss, with parenteral nutrition only when enteral feeding is not possible.
• Differentiated conditions need specific treatment:
  • Cannabinoid hyperemesis syndrome:
    • complete and sustained cessation of cannabis (symptoms improve over 1 to 2 weeks and may take months to settle)
    • hot showers for temporary relief
    • capsaicin 0.025 to 0.1% cream applied to the abdomen
    • haloperidol 0.5 to 5 mg IV or orally (single dose in acute care)
    • amitriptyline 10 to 50 mg at night for prevention
  • Cyclic vomiting syndrome:
    • Prophylaxis with amitriptyline 10 to 25 mg at night, increased to 50 to 100 mg, or topiramate 25 mg at night, titrated to 100 mg, or propranolol 10 to 40 mg 3 times daily.
    • Abortive therapy with ondansetron 8 mg sublingually, sumatriptan 20 mg nasally or 6 mg subcutaneously, and sedation with lorazepam 0.5 to 1 mg at the onset of episodes.
  • Rumination syndrome: diaphragmatic breathing and behavioural therapy.
  • Eating disorders: specialist psychiatric and nutritional care.
  • Gastroparesis: dietary changes, glycaemic control, and prokinetic therapy.
• Special groups:
  • Pregnancy: vomiting in pregnancy needs exclusion of other causes (urinary tract infection, hyperthyroidism). Treatment is pyridoxine 10 to 25 mg 3 to 4 times daily, doxylamine 10 mg with pyridoxine 10 mg 2 to 4 times daily, promethazine 12.5 to 25 mg 8 hourly, or ondansetron 4 mg 8 hourly when needed.
  • In hyperemesis, give intravenous fluids and thiamine. Avoid neuromodulators unless essential.
  • Children: exclude organic disease, obstruction, metabolic disease (inborn errors), intracranial disease, and cyclic vomiting. Use rehydration, ondansetron 0.1 to 0.15 mg/kg per dose (maximum 8 mg), and psychological therapy.
  • Elderly: review medicines (digoxin, opioids, antibiotics, metformin), investigate for malignancy, ischaemia, and cardiac disease, and use lower doses of antiemetics (metoclopramide) and neuromodulators. Check electrolytes and renal function.
  • Diabetes: assess for gastroparesis and ketoacidosis, review GLP-1 receptor agonists and metformin, and monitor glucose.
  • Cardiac disease and QT prolongation: avoid ondansetron, domperidone, and citalopram at high doses, and check the electrocardiogram and electrolytes.
  • Renal and hepatic impairment: reduce doses (metoclopramide half dose in renal impairment, ondansetron maximum 8 mg per day in severe hepatic impairment).
• Follow up: review in 1 to 2 weeks after acute episodes, then every 4 to 8 weeks to assess vomiting frequency, weight, hydration, electrolytes, and mood, and monitor for adverse effects.
• Refer to a gastroenterologist for refractory symptoms, weight loss, or complications, to a psychiatrist or psychologist for eating disorders and anxiety, and to neurology for suspected cyclic vomiting or intracranial disease.