Causality assessment · Expected pharmacological effect

Hydrochlorothiazide (thiazides) and Hyponatraemia: is the FAERS signal real?

n=2,897 co-reports · PRR 7.8 · ROR 8.0

Hydrochlorothiazide (thiazides) side-effect profile All assessments See in the full list

A written Bradford Hill assessment of one drug–event pair. The grade is a judgement about the signal, not a statement that this drug causes this event in any one person; FAERS counts are reports, not rates.

Expected pharmacological effect

Hydrochlorothiazide (thiazides) ↔ Hyponatraemia

n=2,897 co-reports · PRR 7.8 · ROR 8.0

Thiazide diuretics are a leading cause of hyponatraemia, particularly in older women, and the effect is a fairly direct consequence of their pharmacology: they impair urinary dilution and, over time, can produce the syndrome of inappropriate antidiuresis. Onset is often within the first few weeks of therapy, and serum sodium usually returns to normal after the drug is stopped. The risk is dose-related and rises with age, low body weight, and use of interacting drugs (SSRIs, carbamazepine), which is why monitoring of electrolytes after starting or changing a thiazide is standard practice. Like spironolactone's potassium effect, this is graded “expected pharmacological effect” — a well-understood class action rather than an unexpected idiosyncratic signal.

Regulatory basis: hydrochlorothiazide/thiazide prescribing information (hyponatraemia and electrolyte-monitoring warnings). Established thiazide-induced hyponatraemia literature.

Bradford Hill viewpoint	Status	Note
Temporality (necessary)	met	Sodium falls during exposure, often in the first weeks, and recovers after withdrawal
Strength	partial	PRR 8, moderate — common in absolute terms but a modest disproportionality
Consistency	met	Reproduced across thiazide agents and in the literature
Specificity	partial	Shared with loop diuretics and other causes of SIADH
Biological gradient	met	Dose-related and worse with age, low body weight, and interacting drugs
Plausibility	met	Impaired urinary dilution / SIADH is the established mechanism
Coherence	met	Coheres with the routine electrolyte monitoring after starting a thiazide
Experiment	met	Sodium normalizes on drug withdrawal — a reliable, reproducible dechallenge
Analogy	met	Analogous to other diuretic-induced electrolyte disturbances

This page's own qualitative read, not an automated/citation-gated assessment.

✗ No ClinicalTrials.gov results-posting trial in the top search hits for hydrochlorothiazide captured hyponatraemia as a tracked adverse-event term. Hyponatraemia is typically captured through routine electrolyte monitoring rather than coded as a trial endpoint, so the evidence base is the prescribing information and observational studies, not trial AE tables.