Which medications can cause hyponatremia in a patient with a serum sodium of 130 mmol/L?

Medications That Cause Hyponatremia

The most common medication classes causing hyponatremia (Na 130 mmol/L) include diuretics (especially thiazides), antidepressants (SSRIs/SNRIs), anticonvulsants (particularly carbamazepine and oxcarbazepine), antipsychotics, and proton pump inhibitors, with elderly patients and those on multiple medications at highest risk. 1, 2

High-Risk Medication Classes

Diuretics

• Thiazide and thiazide-like diuretics are among the most frequent causes of drug-induced hyponatremia, particularly in elderly patients 3, 2
• Loop diuretics can also cause hyponatremia through excessive sodium and water loss, though less commonly than thiazides 2
• The risk increases substantially when diuretics are combined with other hyponatremia-inducing medications 1

Antidepressants

• SSRIs (selective serotonin reuptake inhibitors) cause hyponatremia in approximately 0.071% of treated patients, with sertraline specifically associated with SIADH 4, 1
• SNRIs (serotonin-norepinephrine reuptake inhibitors) have an even higher incidence at 0.088%, with venlafaxine carrying explicit FDA warnings about hyponatremia risk 5, 1
• The mechanism involves inappropriate antidiuretic hormone secretion (SIADH), with cases documented below 110 mmol/L 4, 5
• Elderly patients taking diuretics or who are volume depleted face substantially greater risk when prescribed these antidepressants 4, 5

Anticonvulsants

• Oxcarbazepine has the highest incidence of any psychotropic medication at 1.661% of treated patients 1
• Carbamazepine follows with 0.169% incidence, also causing SIADH 1, 3
• Both medications should be used with extreme caution in patients with other risk factors 1

Antipsychotics

• Antipsychotic medications can induce hyponatremia, though at significantly lower rates than anticonvulsants or antidepressants 1, 3
• The mechanism typically involves SIADH 3

Proton Pump Inhibitors

• PPIs increase hyponatremia risk through multiple mechanisms: promoting small intestine bacterial overgrowth, impairing micronutrient absorption, and directly causing hyponatremia 6
• In cirrhotic patients, PPIs significantly increase hepatic encephalopathy risk, partly mediated through worsening hyponatremia 6

Other Medications

• ACE inhibitors and angiotensin II receptor blockers substantially increase hyponatremia risk when combined with other causative drugs 1
• Chlorpropamide (sulfonylurea) is an established cause of SIADH 3
• NSAIDs can precipitate SIADH, particularly in elderly patients 3
• Vasopressin and its analogues directly cause water retention and hyponatremia 3

High-Risk Patient Populations

Elderly Patients

• Age ≥65 years represents the single greatest risk factor for medication-induced hyponatremia 4, 5, 1
• Elderly patients have impaired free water excretion and are more susceptible to SIADH 3
• Female SSNRI users aged ≥65 years on concomitant hyponatremia-inducing drugs represent the highest-risk subgroup 1

Polypharmacy

• Concomitant use of multiple hyponatremia-inducing medications increases risk 16-42 fold compared to single-agent therapy 1
• Common high-risk combinations include antidepressants plus diuretics, or antidepressants plus ACE inhibitors/ARBs 1

Volume-Depleted Patients

• Patients taking diuretics or who are otherwise volume depleted face markedly elevated risk when prescribed SSRIs or SNRIs 4, 5

Clinical Presentation and Timing

• Hyponatremia typically develops after a median of 7 days following drug initiation or dose increase 1
• 57.1% of cases present symptomatically, with 19% showing severe symptoms including seizures and vomiting 1
• Symptoms range from mild (nausea, headache, weakness) to severe (confusion, seizures, coma, respiratory arrest, death) 4, 5, 7

Pathophysiologic Mechanisms

• SIADH is the predominant mechanism for most drug-induced hyponatremia, characterized by inappropriate ADH secretion despite low plasma osmolality 3, 2
• Diuretics cause hyponatremia through direct sodium loss and volume depletion 2
• Some medications impair free water excretion through multiple pathways 2

Management Approach

Immediate Actions

• Discontinue the offending medication(s) as the primary intervention 3
• Assess symptom severity: patients with Na <125 mmol/L and severe symptoms require emergency 3% hypertonic saline 7
• Never correct chronic hyponatremia faster than 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome 8

Additional Measures

• Fluid restriction to 1-1.5 L/day for euvolemic or hypervolemic patients 8, 7
• Normal saline infusions for hypovolemic hyponatremia 7
• Close monitoring of serum sodium levels, particularly in the first 24-48 hours after drug discontinuation 3

Prevention Strategies

• Identify high-risk patients before prescribing known causative medications 1
• Check baseline sodium levels in elderly patients, those on diuretics, or those receiving multiple medications 1
• Monitor sodium levels within the first 1-2 weeks after starting high-risk medications 1
• Educate patients about symptoms requiring immediate medical attention 4, 5

Critical Pitfalls to Avoid

• Failing to recognize drug-induced hyponatremia in polypharmacy patients, where multiple confounding factors obscure the diagnosis 9
• Continuing the offending medication while attempting to correct sodium with other interventions 3
• Overly rapid correction exceeding 8 mmol/L in 24 hours, risking osmotic demyelination syndrome 8, 7
• Ignoring mild hyponatremia (130-134 mmol/L) in high-risk patients, as this can progress to severe, symptomatic hyponatremia 7
• Prescribing SSRIs/SNRIs to elderly patients on diuretics without sodium monitoring 4, 5, 1