What could be the cause of hyponatremia (low sodium levels) and hypomagnesemia (low magnesium levels) in an elderly male patient with idiopathic neuropathy on gabapentin (Neurontin) and buspirone (Buspar)?

Hyponatremia and Hypomagnesemia in an Elderly Male on Gabapentin and Buspirone

Primary Cause: Gabapentin-Induced Electrolyte Disturbances

Gabapentin is the most likely culprit for both the hyponatremia and hypomagnesemia in this elderly patient, as gabapentinoids are established causes of syndrome of inappropriate antidiuretic hormone secretion (SIADH) and can contribute to magnesium depletion, particularly in older adults with age-related renal impairment. 1, 2

Mechanism and Risk Factors

Hyponatremia from Gabapentin

• Gabapentin causes SIADH through inappropriate antidiuretic hormone secretion, leading to euvolemic hyponatremia 1, 2
• Elderly patients are at significantly higher risk for drug-induced hyponatremia, with advanced age being one of the most recognized risk factors 3, 2
• Gabapentin is "substantially excreted by the kidney," and elderly patients are more likely to have decreased renal function, increasing the risk of toxic reactions and electrolyte disturbances 4
• The drug accumulates in patients with compromised renal function, which is common in elderly males, amplifying adverse effects including electrolyte abnormalities 4

Hypomagnesemia Considerations

• Hypomagnesemia frequently coexists with hyponatremia and can make correction of other electrolytes difficult until magnesium is addressed 5, 6
• Magnesium deficiency causes renal potassium wasting and can perpetuate electrolyte imbalances 5
• While gabapentin is not classically associated with isolated hypomagnesemia, the combination of advanced age, potential renal impairment, and polypharmacy increases risk 3

Buspirone's Role

• Buspirone is not a recognized cause of hyponatremia or hypomagnesemia in the medical literature
• However, polypharmacy itself is highly prevalent in elderly patients and increases overall risk of electrolyte disorders 7

Critical Diagnostic Workup

Immediate Laboratory Assessment

• Serum osmolality, urine osmolality, and urine sodium to confirm SIADH (expect serum osmolality <280 mOsm/kg, urine osmolality >100 mOsm/kg, urine sodium >40 mEq/L) 2
• Assess severity of hyponatremia: mild (130-134 mmol/L), moderate (125-129 mmol/L), or severe (<125 mmol/L) 2
• Magnesium level to quantify severity: severe hypomagnesemia is <1.0 mEq/L 6
• Renal function (creatinine clearance) as gabapentin dosing must be adjusted based on renal function in elderly patients 4
• ECG to assess for prolonged QT interval, prominent U waves, or arrhythmias from hypomagnesemia 6

Rule Out Alternative Causes

• Diuretic use is the most common cause of hyponatremia in clinical practice, though not mentioned in this case 5, 3
• Volume status assessment to distinguish SIADH (euvolemic) from other causes 2
• Thyroid and adrenal function if SIADH criteria not met 2
• Other medications that cause hyponatremia include antidepressants, NSAIDs, and proton pump inhibitors 2, 7

Management Algorithm

Step 1: Assess Clinical Urgency

• If severe hyponatremia (<125 mmol/L) with neurological symptoms (confusion, seizures, altered mental status): this is a medical emergency requiring hypertonic saline 2
• If severe hypomagnesemia (<1.0 mEq/L): urgent IV magnesium sulfate replacement required (1-2 g IV bolus, then continuous infusion) due to risk of torsades de pointes and ventricular fibrillation 6
• If ECG shows QT prolongation or arrhythmias: immediate cardiac monitoring and magnesium replacement 6

Step 2: Discontinue or Adjust Gabapentin

• Discontinue gabapentin immediately if SIADH is confirmed and hyponatremia is moderate to severe 1
• If gabapentin must be continued for neuropathy control, reduce dose based on creatinine clearance 4
• Consider alternative neuropathic pain agents: duloxetine (60 mg once daily) or tricyclic antidepressants (nortriptyline 25 mg at bedtime, titrated cautiously) are first-line alternatives 8

Step 3: Correct Electrolyte Abnormalities

For Hyponatremia:

• Mild asymptomatic hyponatremia (130-134 mmol/L): fluid restriction to 800-1000 mL/day and discontinue offending agent 2
• Moderate hyponatremia (125-129 mmol/L): fluid restriction plus possible hypertonic saline if symptomatic 2
• Monitor sodium correction rate: do not exceed 8-10 mEq/L in 24 hours to avoid osmotic demyelination syndrome 2

For Hypomagnesemia:

• Correct magnesium BEFORE attempting to correct other electrolytes, as hypomagnesemia makes potassium repletion difficult 5, 6
• Severe hypomagnesemia: 1-2 g IV magnesium sulfate bolus, then continuous infusion 6
• Mild-moderate: oral magnesium supplementation (magnesium oxide 400 mg twice daily) 6

Step 4: Monitor Response

• Recheck sodium and magnesium within 24-48 hours after discontinuing gabapentin 1
• Pregabalin-induced SIADH (a related gabapentinoid) shows rapid improvement after drug discontinuation, suggesting gabapentin will behave similarly 1
• Continue monitoring until electrolytes normalize and remain stable 2

Common Pitfalls to Avoid

• Failing to recognize elderly patients are at highest risk for drug-induced electrolyte disorders, particularly with renally-excreted medications like gabapentin 4, 3
• Overlooking magnesium deficiency when treating hyponatremia, which can perpetuate electrolyte imbalances 5
• Correcting sodium too rapidly (>8-10 mEq/L per 24 hours), risking osmotic demyelination syndrome 2
• Not adjusting gabapentin dose for renal function in elderly patients, leading to drug accumulation and toxicity 4
• Assuming buspirone is the cause when gabapentin is the more likely culprit based on established mechanisms 1, 2

Alternative Neuropathic Pain Management

If gabapentin must be discontinued:

• First-line alternatives: Duloxetine 30 mg once daily for 1 week, then 60 mg once daily (most evidence-based for neuropathy) 8
• Second-line: Nortriptyline 25 mg at bedtime, titrated by 25 mg every 3-7 days (obtain ECG if >40 years old) 8
• Third-line: Topical lidocaine 5% patches for localized neuropathy 8
• Avoid pregabalin as it shares the same mechanism and risk profile as gabapentin 1