What is the likely cause of hyponatremia in a patient with a history of depression on fluoxetine (fluoxetine), following an acute left-sided middle cerebral artery stroke?

Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

The patient's hyponatremia is most likely caused by SIADH, with dual contributing factors: fluoxetine therapy and the acute ischemic stroke itself. 1, 2, 3

Diagnostic Reasoning

The laboratory findings definitively establish SIADH as the diagnosis:

• Low serum sodium (119 mEq/L) with low serum osmolality (251 mOsm/kg) indicates true hypotonic hyponatremia, ruling out pseudohyponatremia 3
• Inappropriately concentrated urine osmolality (349 mOsm/kg) relative to low serum osmolality is the hallmark of SIADH 2, 3
• Elevated urine sodium (45 mEq/L) indicates continued renal sodium excretion despite hyponatremia 2, 3
• Clinical euvolemia (moist mucous membranes, no skin tenting, no edema) excludes both hypovolemic and hypervolemic causes 4, 3

Why Not the Other Diagnoses?

Cerebral salt wasting is excluded because the patient shows clear clinical euvolemia. Cerebral salt wasting causes hypovolemia with volume depletion through excessive natriuresis, which would manifest as dry mucous membranes, skin tenting, and potentially hypotension 4, 2. This patient has stable vital signs and normal volume status on examination 4, 3.

Diabetes insipidus is excluded because it causes hypernatremia (not hyponatremia) with dilute urine, the exact opposite of this patient's presentation 3.

While stroke alone can cause SIADH, the presence of fluoxetine therapy creates a dual etiology scenario that significantly increases risk 1, 2, 3, 5.

Dual Etiology: Fluoxetine and Stroke

Fluoxetine is a well-established cause of SIADH. The FDA label explicitly warns that "hyponatremia may occur as a result of treatment with SSRIs and SNRIs, including Prozac. In many cases, this hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Cases with serum sodium lower than 110 mmol/L have been reported." 1

Acute ischemic stroke independently causes SIADH in a substantial proportion of patients. In a large prospective study of 1000 stroke patients, 67% of those with hyponatremia had SIADH, with ischemic stroke accounting for 83 cases 2. The mechanism involves damage to hypothalamic-pituitary pathways that regulate ADH secretion 3, 6.

The combination of fluoxetine and acute stroke creates additive risk. Both conditions independently cause non-osmotic ADH release, and their simultaneous presence in this patient on ICU day 3 (when stroke-related SIADH typically manifests) explains the severe hyponatremia 1, 2, 3.

Clinical Significance and Timing

The timing is consistent with stroke-related SIADH, which typically develops 3-7 days post-stroke, coinciding with this patient's ICU day 3 presentation 2, 3. However, fluoxetine-induced SIADH can occur within 9 days of initiation and may develop at any point during chronic therapy 5.

This degree of hyponatremia (119 mEq/L) is severe and clinically significant. While the patient currently has only expressive aphasia (which is attributable to the left MCA stroke), severe hyponatremia can cause additional neurological deterioration including confusion, seizures, and altered mental status 1, 5. The FDA label notes that cases with sodium below 110 mmol/L have been reported with fluoxetine, and this patient is approaching that threshold 1.

Management Implications

Fluoxetine should be discontinued immediately given its contribution to severe SIADH 1, 5. The FDA label states "discontinuation of Prozac should be considered in patients with symptomatic hyponatremia and appropriate medical intervention should be instituted" 1.

Fluid restriction is the cornerstone of SIADH management in stroke patients, though the American Heart Association guidelines note that treatment modifications are required for patients with SIADH 4. For severe symptomatic hyponatremia at this level, hypertonic saline (3%) may be required for controlled correction 4, 3.

Avoid hypotonic fluids entirely. The American Heart Association explicitly recommends isotonic saline (0.9% NaCl) for acute stroke patients and warns that hypotonic solutions like 5% dextrose or 0.45% saline distribute into intracellular spaces and worsen cerebral edema 4, 7.

Common Pitfall

Do not confuse SIADH with cerebral salt wasting in stroke patients. While both cause hyponatremia with elevated urine sodium, the critical distinguishing feature is volume status: SIADH presents with euvolemia while cerebral salt wasting presents with hypovolemia and requires aggressive volume resuscitation rather than fluid restriction 4, 2, 3. Misdiagnosing SIADH as cerebral salt wasting and administering aggressive fluid resuscitation would dangerously worsen the hyponatremia 3.