What is the cause of hyponatremia in a patient with normal labs, except for a Glomerular Filtration Rate (GFR) of 76, and who is taking escitalopram (escitalopram), metformin (metformin), atorvastatin calcium (atorvastatin), losartan (losartan), clopidogrel (clopidogrel), and gabapentin (gabapentin)?

Hyponatremia in a 75-Year-Old Patient: Cause and Management

Most Likely Cause: Escitalopram-Induced SIADH

The hyponatremia (sodium 131 mEq/L) in this patient is most likely caused by escitalopram, which is a well-established cause of SIADH (Syndrome of Inappropriate Antidiuretic Hormone secretion). 1, 2, 3

Why Escitalopram is the Primary Culprit

• SSRIs like escitalopram are among the most common medication causes of hyponatremia in clinical practice, with the FDA label specifically warning that "hyponatremia may occur as a result of treatment with SSRIs" and that it "appears to be the result of SIADH" 1
• The mechanism involves intrarenal activation of water reabsorption through upregulation of aquaporin-2 channels, leading to nephrogenic SIADH (NSIAD) 4
• Risk is significantly elevated in this patient due to multiple factors: age >65 years, concurrent diuretic use (losartan has mild diuretic effects), and the sodium level being in the lower range 5
• Hyponatremia from SSRIs typically appears within the first month of treatment but can occur at any time, is not dose-dependent, and resolves when the medication is discontinued 5

Other Medications Assessed

• Losartan: While ACE inhibitors and ARBs can rarely cause hyponatremia, this is uncommon and typically occurs in the context of volume depletion 3
• Gabapentin: Has been reported to cause hyponatremia but is much less frequently implicated than SSRIs 2
• Metformin, atorvastatin, clopidogrel: Not established causes of hyponatremia 2, 3

Dietary Contribution Assessment

• Diet is unlikely to be the primary cause given the patient's sodium level of 131 mEq/L, which represents true hyponatremia requiring medication adjustment 6
• However, if the patient has very low salt intake combined with high free water consumption, this could be a contributing factor 7

Diagnostic Workup Required

Before initiating treatment, obtain the following tests to confirm SIADH and rule out other causes: 6, 8

• Serum osmolality (expect <275 mOsm/kg in SIADH)
• Urine osmolality (expect >500 mOsm/kg in SIADH)
• Urine sodium (expect >20-40 mEq/L in SIADH)
• Serum uric acid (<4 mg/dL has 73-100% positive predictive value for SIADH) 8, 9
• TSH and morning cortisol to rule out hypothyroidism and adrenal insufficiency 6
• Volume status assessment through physical examination (looking for orthostatic hypotension, dry mucous membranes, edema, or ascites) 6, 8

Expected Findings in Escitalopram-Induced SIADH

• Euvolemic state (no edema, no orthostatic hypotension, normal skin turgor) 8
• Urine sodium >20-40 mEq/L despite hyponatremia 8
• Inappropriately concentrated urine (osmolality >500 mOsm/kg) relative to low serum osmolality 8

Treatment Algorithm

Step 1: Discontinue Escitalopram Immediately

The most important intervention is to stop escitalopram, as hyponatremia from SSRIs is reversible upon discontinuation. 1, 5

• Taper gradually over 1-2 weeks to avoid discontinuation syndrome (dysphoria, dizziness, sensory disturbances, anxiety) 1
• Monitor sodium levels every 2-3 days initially after discontinuation 6

Step 2: Implement Fluid Restriction

For mild, asymptomatic hyponatremia (sodium 131 mEq/L), fluid restriction to 1000 mL/day is the cornerstone of treatment. 6, 8

• This is appropriate for euvolemic hyponatremia (SIADH) 6
• Continue restriction until sodium normalizes (>135 mEq/L) 6

Step 3: Consider Oral Sodium Supplementation

If sodium does not improve with fluid restriction alone after 48-72 hours, add oral sodium chloride 100 mEq (approximately 6 grams) three times daily. 6

• Use pharmaceutical-grade sodium chloride tablets, not home-prepared solutions 6
• Monitor sodium levels every 2-3 days during supplementation 6

Step 4: Alternative Antidepressant Selection

If antidepressant therapy is still needed, consider alternatives with lower hyponatremia risk: 2, 5

• Bupropion (lowest risk among antidepressants)
• Mirtazapine (lower risk than SSRIs)
• Avoid all SSRIs and SNRIs as they carry similar hyponatremia risk 2, 5
• Monitor sodium levels weekly for the first month after starting any new antidepressant 5

Step 5: Monitoring Schedule

• Check sodium every 2-3 days initially after discontinuing escitalopram 6
• Once sodium reaches 133-135 mEq/L, check weekly for 1 month 6
• If starting a new antidepressant, check sodium at 1,2, and 4 weeks, then monthly for 3 months 5

Critical Safety Considerations

Correction Rate Limits

Even though this patient has mild hyponatremia, correction must not exceed 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome. 6, 7

• For a 75-year-old patient, aim for even slower correction of 4-6 mmol/L per day 6
• This patient is at higher risk for osmotic demyelination due to advanced age 6

When to Use Hypertonic Saline (3%)

Do NOT use hypertonic saline in this patient as sodium is 131 mEq/L and the patient is asymptomatic 6, 7

• Hypertonic saline is reserved for severe symptomatic hyponatremia (sodium <120 mEq/L with seizures, altered mental status, or coma) 6, 7

Red Flags Requiring Emergency Treatment

Seek immediate medical attention if the patient develops: 6, 1

• Confusion, altered mental status, or delirium
• Seizures
• Severe headache or vomiting
• Unsteadiness or falls
• Sodium drops below 125 mEq/L

Common Pitfalls to Avoid

• Do not ignore mild hyponatremia (130-135 mEq/L) as it increases fall risk 4-fold (21% vs 5%) and mortality 60-fold (11.2% vs 0.19%) 6
• Do not administer normal saline in euvolemic hyponatremia (SIADH), as this will worsen hyponatremia by providing free water 6
• Do not "rechallenge" with escitalopram or switch to another SSRI, as cross-reactivity is common and the patient should be informed to avoid all SSRIs 2, 5
• Do not correct sodium too rapidly (>8 mmol/L in 24 hours), especially in elderly patients 6, 7
• Do not delay treatment while pursuing extensive diagnostic workup if the clinical picture clearly suggests SIADH 7

Expected Timeline for Resolution

• Sodium should begin improving within 48-72 hours of discontinuing escitalopram and implementing fluid restriction 5
• Full normalization typically occurs within 5-7 days after stopping the offending medication 5
• If sodium does not improve within 3-4 days, reassess for other contributing causes or consider adding oral sodium supplementation 6