Can quetiapine (antipsychotic medication) cause hyponatremia, especially in vulnerable populations such as the elderly or those with impaired renal function?

Can Quetiapine Cause Hyponatremia?

Yes, quetiapine can cause hyponatremia through the syndrome of inappropriate antidiuretic hormone secretion (SIADH), and this risk is particularly elevated in vulnerable populations including the elderly, those with impaired renal function, and patients with primary polydipsia. 1, 2, 3

Evidence for Quetiapine-Induced Hyponatremia

Established Association

• Antipsychotic medications as a class, including quetiapine, are associated with hyponatremia, with an adjusted reporting odds ratio of 1.58 (95% CI 1.46-1.70) compared to other medications 1
• When antipsychotics are used without other hyponatremia-causing medications, the association strengthens significantly (ROR 3.00,95% CI 2.65-3.39), suggesting the risk is often underestimated when polypharmacy is present 1
• The mechanism involves SIADH, where quetiapine stimulates inappropriate vasopressin secretion, impairing the kidney's ability to excrete free water 2, 4

Clinical Presentation and Severity

• Quetiapine-induced hyponatremia can present with severe neurological symptoms including generalized tonic-clonic seizures, confusion, vomiting, altered consciousness, and in extreme cases, cerebral edema requiring ICU admission 2, 4
• Extreme hyponatremia (sodium as low as 97 mmol/L) has been documented when quetiapine-induced SIADH combines with primary polydipsia, creating a life-threatening scenario 4
• The combination of SIADH from quetiapine plus excessive water intake prevents compensatory free water excretion, leading to severe dilutional hyponatremia 4

High-Risk Populations Requiring Enhanced Monitoring

Elderly Patients

• Elderly patients face substantially elevated hyponatremia risk due to age-related decreases in left ventricular compliance, reduced glomerular filtration rate, decreased baroreceptor sensitivity, and reduced total body water 5
• The American Geriatrics Society identifies tramadol as causing hyponatremia/SIADH 6, and while quetiapine is not explicitly listed in the Beers Criteria for this indication, the broader class effect is well-established 1, 3
• Elderly patients have more vulnerable water homeostasis with shifts toward increased extracellular and decreased intracellular water, making them prone to both hypo- and hypervolemia 5

Patients with Schizophrenia and Primary Polydipsia

• Patients with schizophrenia are particularly susceptible to hyponatremia due to the close association between this condition and primary polydipsia (compulsive water drinking) 4, 3
• Primary polydipsia was present in 67% of antipsychotic-associated hyponatremia cases, with an additional 10% developing drug-induced polydipsia after antipsychotic initiation 3
• The combination of primary polydipsia and quetiapine-induced SIADH creates a "perfect storm" where excessive water intake meets impaired water excretion 4

Patients with Impaired Renal Function

• Renal impairment compounds hyponatremia risk through reduced capacity for electrolyte regulation and altered drug clearance 5
• Confusion and delirium are more common during somatic illness in geriatric patients with electrolyte disturbances, making early detection crucial 5

Clinical Monitoring Algorithm

Baseline Assessment Before Quetiapine Initiation

• Check baseline serum sodium, electrolytes, and renal function (creatinine, eGFR) before starting quetiapine 5
• Screen for history of primary polydipsia, excessive water intake, or previous hyponatremia episodes 4, 3
• Document concurrent medications that may cause hyponatremia, particularly thiazide diuretics, SSRIs, and other psychotropics 6, 7

Monitoring During Quetiapine Therapy

• Recheck serum sodium within 1-2 weeks after quetiapine initiation or dose escalation, particularly in elderly patients or those with risk factors 7, 5
• Monitor more frequently (within 3-7 days) in patients with multiple risk factors: elderly, renal impairment, polydipsia, or concurrent hyponatremia-causing medications 7
• Test immediately if psychiatric or physical condition deteriorates with symptoms of confusion, lethargy, nausea, headache, or seizures 1, 2, 8

Critical Warning Signs

• Sodium <130 mmol/L requires immediate intervention and consideration of quetiapine dose reduction or discontinuation 7
• Sodium <125 mmol/L is a medical emergency requiring specialist consultation 7
• Sodium <105 mmol/L carries increased risk of osmotic demyelination syndrome if corrected too rapidly; correction should not exceed 8 mmol/L in 24 hours 4

Management Approach

When Hyponatremia is Detected

• Immediately assess severity and symptoms: mild (130-135 mmol/L), moderate (125-129 mmol/L), or severe (<125 mmol/L) 7
• For symptomatic hyponatremia with neurological symptoms, treat as medical emergency with hypertonic 3% saline boluses (100 mL) under continuous monitoring 4
• Implement fluid restriction (typically 800-1000 mL/day) as first-line management for SIADH-induced hyponatremia 4, 8
• Reduce or discontinue quetiapine depending on severity and clinical necessity, weighing psychiatric stability against electrolyte risk 8

Preventing Recurrence

• Consider alternative antipsychotic agents if quetiapine must be discontinued, though all antipsychotics carry some hyponatremia risk 1, 3
• Address primary polydipsia through behavioral interventions and close monitoring of fluid intake 4, 3
• Avoid combining quetiapine with other medications that cause hyponatremia when possible, particularly thiazide diuretics and SSRIs 6, 7

Common Pitfalls to Avoid

• Do not attribute confusion or altered mental status solely to psychiatric illness without checking sodium levels in patients on quetiapine 1, 2, 8
• Do not overlook the additive risk when quetiapine is combined with other hyponatremia-causing medications, as the association may be masked by polypharmacy 1
• Do not correct severe hyponatremia too rapidly (>8 mmol/L in 24 hours), as this risks osmotic demyelination syndrome 4
• Do not assume newer atypical antipsychotics are safer regarding hyponatremia risk; both older and newer agents have been implicated 3

Key Takeaway

The incidence of quetiapine-induced hyponatremia may be substantially higher than currently recognized 3, making routine electrolyte monitoring essential, particularly during the first weeks of therapy and in vulnerable populations. Early recognition through systematic monitoring can prevent progression to life-threatening hyponatremia and its neurological complications 1, 2, 4, 8.