Chronic Nausea: Causes (Stomach, Drugs, Hormones, Nervous System) and How It Is Diagnosed

The 2016 Rome IV classification lists, among gastroduodenal disorders, three nausea and vomiting disorders: chronic nausea and vomiting syndrome, cyclic vomiting syndrome and cannabinoid hyperemesis syndrome. Rumination syndrome forms a separate group. A diagnosis of one of these functional disorders is possible only after organic, metabolic and drug-related causes have been excluded, and the criteria rest on duration and character of symptoms.

In practice this means that ‘functional nausea’ is not a first-choice diagnosis. First one must check whether medicines, a disease of the digestive tract, endocrine disorders or neurological causes explain it. Only when a suitably chosen set of tests shows no cause can one speak of a functional disorder — and even then the doctor will judge whether the symptoms fully meet the Rome IV criteria.

Gastroparesis is delayed gastric emptying without mechanical obstruction of the gastric outlet, presenting with nausea, vomiting, early satiety, bloating and pain or discomfort in the upper abdomen. According to a review published in JAMA, the prevalence of definite gastroparesis (with documented delayed emptying) was estimated in one insurance-claims study at 21.5 cases per 100,000 people, and the disease is 2–4 times more common in women than in men. In a large epidemiological study of 82.6 million patients, the commonest causes were type 2 diabetes (51.7%), the effects of surgery (15%), medicines (11.8%), an idiopathic cause (11.3%) and type 1 diabetes (5.7%).

Other risk factors include neurological disease (for example Parkinson’s disease), hypothyroidism, amyloidosis, connective tissue disease (for example scleroderma) and viral infections. Diagnosis requires demonstrating delayed gastric emptying on a test (gastric emptying scintigraphy or an isotope breath test) after a mechanical obstruction has been excluded by gastroscopy or imaging. Treatment includes stopping drugs that delay emptying (opioids, cannabinoids, anticholinergic drugs, GLP-1 analogues), optimising glycaemic control in people with diabetes, a small-particle diet low in fat and insoluble fibre, and antiemetic and prokinetic drugs — this is the full picture described in the guidelines and requires management by a gastroenterologist.

Apart from gastroparesis, nausea accompanies peptic ulcer disease (which we cover in a separate article on stomach and duodenal ulcer), reflux, functional dyspepsia (more in the article on functional dyspepsia), gallstones, pancreatitis, coeliac disease and food intolerances. Gastroscopy, described in the knowledge base entry, is usually the first test when nausea comes with alarm features, vomiting or upper abdominal complaints.

An important clinical problem is that nausea and vomiting often occur despite normal gastric emptying. The Gastroparesis Clinical Research Consortium study analysed 425 patients with chronic nausea and vomiting; 319 (75%) had delayed gastric emptying and 106 had normal emptying.

What follows for the patient? First, symptom severity relates poorly to the result of a gastric emptying test, so a normal result does not mean the nausea is ‘made up’. Second, delayed emptying does not explain all nausea — which is why scintigraphy alone does not close the work-up. Third, this observation comes from a registry of specialist centres and does not translate directly to the average patient at a family doctor’s surgery.

A review of medicines is the cheapest and often the most effective diagnostic step. Nausea is a common adverse effect of many preparations: metformin, iron, antibiotics, some antidepressants (SSRIs), opioids, non-steroidal anti-inflammatory drugs, oral hormonal preparations, high-dose supplements (for example zinc, or magnesium in some forms) and GLP-1 analogues used in diabetes and obesity. Pay attention to timing: did the nausea begin after a new drug was started or a dose increased?

GLP-1 analogues (for example semaglutide, and with a similar effect tirzepatide, which we cover in the knowledge base) also cause nausea. In a review of the STEP programme of semaglutide in obesity, the commonest adverse events were gastrointestinal, which were transient, mild to moderate and usually resolved without permanent discontinuation. These drugs also slow gastric emptying, which is why in the work-up for gastroparesis the doctor takes their use into account. Never stop or change doses of long-term drugs on your own — a correction is decided by the doctor.

Nausea can be a symptom of endocrine and metabolic disorders that are easily missed without blood tests. They include an underactive thyroid (which can also slow the gut; we cover hypothyroidism in the knowledge base), adrenal insufficiency (we cover the role of cortisol in a separate entry), hypercalcaemia, diabetes with glycaemic disturbance, kidney and liver disease and electrolyte disorders. In such situations nausea is often accompanied by other symptoms: fatigue, weight loss or gain, thirst, constipation, weakness.

That is why the basic set of tests for chronic nausea usually includes a blood count, glucose, electrolytes, kidney and liver parameters, calcium, TSH and — depending on symptoms — lipase and possibly other tests. We write about interpreting TSH in the entry on thyroid hormones. In women of reproductive age, the first step is a pregnancy test.

Nausea is a frequent symptom of migraine — not only during the headache but sometimes as the only troublesome symptom. Disorders of the inner ear and balance system, accompanied by dizziness, and nausea with motion work by a similar mechanism. We write about migraine in the knowledge base and about dizziness in a separate article. If nausea occurs together with dizziness, tinnitus or a change in hearing, it is worth seeing the treating doctor, and with neurological symptoms — immediately.

A significant group of patients have nausea linked to anxiety and stress. The gut-brain axis means that strong emotional tension can provoke nausea and abdominal pain, and chronic nausea itself intensifies anxiety — a vicious circle forms. This does not mean the nausea is ‘in the head’: these are real physiological symptoms. Recognising anxiety as a factor, however, needs specialist assessment and should not precede the exclusion of somatic causes. We write about the effect of chronic stress on the body in the knowledge base.

Cannabinoid hyperemesis syndrome (CHS) is a form of cyclic vomiting associated with regular cannabis use. We write about it neutrally because it is often missed in the history and its recognition changes treatment. A systematic review found that in the cases described all patients used cannabis regularly and had cyclic nausea and vomiting, in 96.8% symptoms resolved after stopping use, in 92.3% there were compulsive hot baths giving relief, in 85.1% abdominal pain, and men made up 72.9%.

For the reader an important distinction applies: not every recurrent vomiting in a person who uses cannabis is CHS, and not every recurrent vomiting is related to cannabis. The evidence comes mainly from case reports, so it is of low quality. An honest conversation with the doctor about substances used is key here and carries no moral judgement. Cyclic vomiting unrelated to cannabis is a separate diagnosis requiring neurological and gastroenterological work-up.

Remember that with many cases of chronic nausea no single cause is found even after full work-up. This is not a failure: a functional diagnosis, when the Rome IV criteria are met, opens the way to symptomatic and behavioural treatment. It is also worth knowing that a gastric emptying result does not precisely predict symptom severity (as the registry study showed).

In the meantime it is not worth using long, strict elimination diets or taking over-the-counter antiemetics ‘just in case’. In the short term, smaller, more frequent, low-fat meals, avoiding smells that worsen nausea and staying hydrated may help — support rather than treatment. People with diabetes should be particularly concerned with achieving good glycaemic control.

Equally untrue is the belief that chronic nausea always points to stomach disease. As the categories above show, medicines, hormones, the nervous system and anxiety all come into play — which is why treating ‘the stomach’ without a work-up so often fails.

Chronic nausea deserves an organised work-up, not blind treatment. The most worthwhile steps come first: a review of medicines and supplements, a pregnancy test in women and basic blood tests. Only then is it worth turning to endoscopy and gastric emptying assessment. It is also worth knowing that even after full work-up some people receive a functional diagnosis — and that diagnosis too has its, though limited, treatments.