In an elderly patient with major depressive disorder taking citalopram 20 mg daily, which adverse effect is most likely?

Hyponatremia is the Most Likely Adverse Effect in Elderly Patients Taking Citalopram

Hyponatremia secondary to syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most clinically significant and common serious adverse effect of citalopram in elderly patients, occurring most frequently within the first 2–4 weeks of therapy. 1, 2, 3

Evidence Supporting Hyponatremia as the Primary Risk

Incidence and Timing

• SSRIs including citalopram are associated with clinically significant hyponatremia specifically in elderly patients, who are at substantially greater risk for this adverse event 1
• The onset of citalopram-induced hyponatremia or SIADH typically ranges from 6 to 20 days after initiation or dose escalation 3
• Most reported cases occur within the first 2–3 weeks of starting therapy, particularly in patients over 60 years of age 2, 4

Risk Factors in This Patient

• Advanced age is the single strongest predictor: elderly patients (≥60 years) demonstrate 23–30% higher citalopram AUC and 30–50% longer half-life compared to younger patients 1
• The 20 mg daily dose is at the maximum recommended for patients over 60 years, increasing exposure risk 1
• Elderly patients have reduced renal clearance and altered volume of distribution, predisposing them to electrolyte disturbances 1

Clinical Presentation

• Symptomatic hyponatremia presents with malaise, progressive confusion, dizziness, falls, weakness, and in severe cases tonic-clonic seizures 2, 3, 4
• Patients are typically euvolemic on examination, distinguishing SIADH from other causes of hyponatremia 2, 3
• Laboratory findings include serum hypoosmolality, urine hyperosmolality, and elevated urine sodium concentration 2, 3, 4

Why Other Options Are Less Likely

Diplopia

• Diplopia is not listed among the common or serious adverse effects of citalopram in elderly patients 1
• No evidence in the FDA label or clinical literature supports diplopia as a characteristic adverse effect of SSRIs in this population 1

Rash

• While rash can occur with any medication, it is not specifically highlighted as a common or serious adverse effect of citalopram in elderly patients 1
• Rash does not demonstrate the age-related increased risk pattern seen with hyponatremia 1

Seizures

• Seizures are not a direct adverse effect of citalopram at therapeutic doses 1
• When seizures occur in elderly patients on citalopram, they are typically secondary to severe hyponatremia (serum sodium <120–125 mEq/L), not a primary drug effect 2, 4
• The case reports documenting seizures in citalopram-treated patients all occurred in the context of profound hyponatremia 2

Critical Monitoring Recommendations

Baseline and Follow-Up

• Obtain baseline serum sodium before initiating citalopram in patients over 60 years 5
• Monitor serum sodium at 1–2 weeks after initiation or dose escalation, as this is the highest-risk period 3, 4, 5
• Continue monitoring throughout the full course of therapy, not just in the first weeks, as late-onset hyponatremia can occur 5

Clinical Surveillance

• Educate patients and caregivers to report malaise, confusion, dizziness, falls, or weakness immediately 2, 3, 4
• Maintain heightened suspicion in patients with additional risk factors: female gender, lower body weight, or concomitant medications that cause SIADH 3

Management of Hyponatremia

• Discontinue citalopram immediately if SIADH is diagnosed 2, 3, 4
• Institute fluid restriction as first-line management 2, 3
• Serum sodium typically normalizes within 5–14 days after discontinuation 3, 4
• Do not rechallenge with citalopram or other SSRIs, as recurrence is likely even with different agents in the same class 5

Common Pitfall to Avoid

The most dangerous error is failing to monitor serum sodium in the first 2–4 weeks of therapy in elderly patients. Because hyponatremia develops insidiously and presents with nonspecific symptoms (confusion, falls, weakness), it is frequently misattributed to age-related decline or other comorbidities rather than recognized as a medication adverse effect 2, 3, 4. This delay in recognition can progress to life-threatening complications including seizures and severe neurological dysfunction 2, 4.