Lamotrigine and Hyponatremia Risk
Lamotrigine (Lamictal) is not a recognized cause of hyponatremia or SIADH based on current evidence. The provided evidence extensively discusses medications that cause SIADH and hyponatremia, but lamotrigine is notably absent from these lists.
Medications That DO Cause SIADH/Hyponatremia
The evidence identifies specific antiepileptic drugs associated with hyponatremia:
- Carbamazepine and oxcarbazepine are well-established causes of SIADH with moderate to high level evidence 1
- These medications should be avoided in older adults due to SIADH risk 1
Other high-risk medication classes include 1, 2:
- SSRIs and SNRIs (incidence 0.5-32% in older adults) 3
- Thiazide diuretics 2
- Chlorpropamide 2
- Antipsychotics 2
- NSAIDs 1, 2
- Tramadol 1
- Chemotherapeutic agents (cisplatin, vinca alkaloids) 1
Why Lamotrigine Is Different
Unlike carbamazepine and oxcarbazepine, lamotrigine does not appear in comprehensive reviews of drug-induced SIADH 1, 2, 4, 5. The evidence specifically lists antiepileptic drugs that cause SIADH, and lamotrigine is not among them 1, 2.
Clinical Implications for High-Risk Patients
Even though lamotrigine itself does not cause hyponatremia, older adults and those with renal impairment remain vulnerable to hyponatremia from other causes 1, 2:
Risk factors for drug-induced hyponatremia include 3:
- Advanced age (decreased baroreceptor sensitivity, reduced total body water, decreased GFR) 6
- Female gender 3
- Concurrent use of diuretics 3
- Low body weight 3
- Lower baseline serum sodium 3
Polypharmacy substantially increases risk when multiple SIADH-inducing medications are combined 1, 6.
Monitoring Recommendations
If a patient on lamotrigine develops hyponatremia, investigate alternative causes 1, 2:
- Review all concurrent medications for known SIADH-inducing agents 1
- Assess for underlying conditions (malignancy, pulmonary disease, CNS disorders) 4
- Evaluate volume status to distinguish SIADH from other causes 1
- Check diagnostic criteria: hyponatremia (<134 mEq/L), plasma hypoosmolality (<275 mosm/kg), inappropriately high urine osmolality (>500 mosm/kg), and elevated urinary sodium (>20 mEq/L) 1, 6
Common Pitfall to Avoid
Do not attribute hyponatremia to lamotrigine without thoroughly investigating other causes, particularly in older adults who may be taking multiple medications known to cause SIADH 1, 2. The combination of thiazide diuretics with SSRIs or other SIADH-inducing medications substantially increases risk 1.