Can Pregabalin Cause Hyponatremia?
Yes, pregabalin can cause hyponatremia through SIADH, though this is a rare adverse effect that requires prompt recognition and discontinuation of the drug.
Mechanism and Evidence
Pregabalin-induced hyponatremia occurs via the syndrome of inappropriate antidiuretic hormone secretion (SIADH), where the drug stimulates inappropriate ADH release despite low serum osmolality, leading to water retention and dilutional hyponatremia 1. While pregabalin's common adverse effects include CNS disturbances, peripheral edema, and weight gain, hyponatremia is an uncommon but documented complication 1.
Clinical Recognition
Monitor for hyponatremia in patients who recently initiated pregabalin therapy, particularly those with:
- Cancer diagnoses (especially lung cancer, where baseline SIADH risk is already elevated at 25-45%) 2, 3
- Neurological conditions requiring anticonvulsant therapy
- Concurrent use of other SIADH-inducing medications (SSRIs, carbamazepine, oxcarbazepine, NSAIDs, opioids, chemotherapy agents) 4, 5
The diagnosis requires confirming euvolemic hyponatremia with inappropriately high urine osmolality (>500 mosm/kg) and elevated urine sodium (>20 mEq/L), while excluding other causes such as adrenal insufficiency 5, 6.
Management Algorithm
For pregabalin-induced SIADH:
Immediate discontinuation of pregabalin - This is the definitive treatment, with rapid improvement typically occurring after drug withdrawal 1
Assess severity and implement appropriate correction:
- Severe symptomatic hyponatremia (Na <120 mEq/L with neurological symptoms): Transfer to ICU, administer 3% hypertonic saline targeting 6 mmol/L correction over 6 hours, never exceeding 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome 5, 6
- Mild-moderate cases: Implement fluid restriction to 1 L/day and ensure adequate oral salt intake 4, 5
Monitor serum sodium every 2 hours initially during active correction, then every 24-48 hours 5, 6
Critical Pitfalls to Avoid
Do not continue pregabalin once SIADH is identified - Unlike chronic SIADH from malignancy where the underlying cause cannot always be eliminated, pregabalin-induced SIADH resolves with drug discontinuation 1.
Avoid combining pregabalin with other SIADH-inducing medications in high-risk patients, as anticonvulsants (particularly carbamazepine and oxcarbazepine), antidepressants, and chemotherapy agents all increase SIADH risk 4, 5.
In cancer patients, distinguish pregabalin-induced SIADH from paraneoplastic SIADH - While both present similarly, the former resolves with drug discontinuation while the latter requires treatment of the underlying malignancy 6, 7. Multiple factors often coexist in cancer patients (69% have multiple contributing factors), so systematic evaluation is essential 4.
Never overcorrect hyponatremia - The 8 mmol/L per 24-hour limit is absolute, with even more cautious rates (4-6 mmol/L per day) recommended in patients with malnutrition, alcoholism, or advanced liver disease 5.