Pregabalin-Induced SIADH and Hyponatremia

Patient Risk Factors

Elderly patients face increased risk for pregabalin-induced hyponatremia due to decreased baroreceptor sensitivity, reduced total body water, age-related decreases in glomerular filtration rate, and susceptibility to adverse effects of medications affecting water balance 1
Renal impairment is a risk factor for pregabalin-induced SIADH, as pregabalin is primarily renally cleared 2, 3
Concurrent use of other medications that can cause SIADH, such as SSRIs, SNRIs, carbamazepine, NSAIDs, and thiazide diuretics, increases the risk of developing SIADH 4
Polypharmacy, particularly in patients with multimorbidity and disability, is also a risk factor for pregabalin-induced SIADH 2, 5

The European Society of Cardiology recommends monitoring for hyponatremia in patients starting pregabalin, especially within the first few weeks of therapy, with diagnostic criteria including hyponatremia (serum sodium < 134 mEq/L), plasma hypoosmolality (< 275 mosm/kg), inappropriately high urine osmolality (> 500 mosm/kg), and inappropriately high urinary sodium concentration (> 20 mEq/L) 4
Clinical manifestations of SIADH include mild symptoms such as anorexia, nausea, and confusion, as well as severe symptoms like seizures, coma, and death, with elderly patients presenting with falls, gait instability, and delirium 1

The American Geriatrics Society recommends discontinuing pregabalin immediately if symptomatic hyponatremia is present, with treatment based on severity, including administration of 3% hypertonic saline for severe symptomatic hyponatremia (sodium < 120 mEq/L with neurological symptoms) 4
The European Heart Journal suggests monitoring serum sodium every 2 hours initially and never exceeding 8 mmol/L correction in 24 hours to prevent osmotic demyelination syndrome 4, 6
For mild to moderate symptomatic hyponatremia or asymptomatic patients with sodium < 120 mEq/L, the American College of Cardiology recommends discontinuing pregabalin, implementing fluid restriction to 1 L/day, and considering oral sodium supplementation 4

Combining pregabalin with other SIADH-inducing medications substantially increases risk, according to the European Society of Cardiology 4
Overly rapid correction of hyponatremia leading to osmotic demyelination syndrome is a critical clinical pitfall to avoid, as recommended by the American Geriatrics Society 4, 6