Can zolpidem (Ambien) cause hyponatremia?

Zolpidem and Hyponatremia

Zolpidem can cause hyponatremia through syndrome of inappropriate antidiuretic hormone secretion (SIADH), as documented in case reports. While not commonly listed among zolpidem's primary adverse effects in major guidelines, there is evidence supporting this association.

Evidence for Zolpidem-Induced Hyponatremia

The most direct evidence comes from a case report documenting zolpidem-induced hyponatremia 1. This report described a patient who developed hyponatremia after taking zolpidem at a dose of 20 mg, with laboratory findings consistent with SIADH. The causality assessment was rated as "probable" according to WHO criteria.

Mechanism and Risk Factors

Zolpidem appears to cause hyponatremia through SIADH, similar to other CNS-active medications. This mechanism involves:

• Inappropriate secretion of antidiuretic hormone
• Decreased serum sodium
• Elevated urine sodium
• Normal urine osmolarity

Risk factors that may increase susceptibility include:

• Elderly patients
• Female gender
• Lower body weight
• Higher doses of zolpidem
• Concomitant use of other medications that can cause hyponatremia

Clinical Implications

When prescribing zolpidem, clinicians should:

1. Consider monitoring serum sodium levels in high-risk patients, particularly:

   • Elderly patients
   • Patients with low body weight
   • Those on multiple medications
   • After initiation or dose increases

2. Be vigilant for early symptoms of hyponatremia:

   • Headache
   • Nausea
   • Vomiting
   • Lethargy
   • Confusion

3. For severe hyponatremia (sodium <130 mmol/L) or symptomatic cases:

   • Discontinue zolpidem
   • Correct sodium levels carefully (not exceeding 8 mmol/L per day) to avoid central pontine myelinolysis
   • Consider alternative hypnotics with lower risk of hyponatremia

Comparison with Other Medications Known to Cause Hyponatremia

While zolpidem has been associated with hyponatremia, other medications have more established associations:

• Thiazide diuretics are responsible for 94% of severe diuretic-induced hyponatremia cases 2
• SSRIs like citalopram have well-documented associations with hyponatremia 3
• Valproate therapy has recognized hyponatremia risk requiring monitoring 4

Monitoring Recommendations

For patients on zolpidem:

• Consider baseline sodium measurement before starting therapy
• Monitor sodium levels after initiation and dose increases in high-risk patients
• Educate patients about early symptoms of hyponatremia
• Maintain appropriate clinical vigilance, especially during the first few weeks of treatment

While zolpidem-induced hyponatremia appears to be uncommon compared to other medications like thiazides or SSRIs, clinicians should remain aware of this potential adverse effect, particularly in vulnerable populations.