Gabapentin and Hyponatremia Risk
Gabapentin can cause hyponatremia, though it carries a significantly lower risk compared to other antiepileptic drugs like carbamazepine, oxcarbazepine, and levetiracetam. 1, 2
Evidence from FDA Labeling and Clinical Studies
The FDA-approved labeling for gabapentin explicitly lists hyponatremia as a postmarketing adverse reaction under "Metabolism and nutrition disorders," confirming this is a recognized complication 1. However, the actual clinical risk appears relatively modest compared to other antiepileptics.
Comparative Risk Assessment
Among antiepileptic drugs, gabapentin demonstrates one of the lowest associations with hyponatremia-related hospitalizations. 2
A large Swedish population-based case-control study (14,359 hyponatremia cases vs 57,383 controls) found:
- Newly initiated gabapentin: adjusted OR 1.61 (95% CI 1.08-2.38) for hospitalization due to hyponatremia 2
- Ongoing gabapentin treatment: adjusted OR 0.83 (95% CI 0.64-1.06) - not statistically significant 2
For comparison, other antiepileptics showed substantially higher risks:
- Carbamazepine: OR 9.63 (newly initiated) 2
- Levetiracetam: OR 9.76 (newly initiated) 2
- Oxcarbazepine: OR 7.97 (ongoing treatment) 2
- Valproate: OR 4.96 (newly initiated) 2
Lamotrigine and gabapentin had the lowest risk both during initiation and ongoing treatment, making them advantageous choices in patients at risk of developing hyponatremia. 2
Clinical Implications and Monitoring
High-Risk Populations Requiring Vigilance
Monitor sodium levels more closely in patients who are:
- Elderly (>65 years), particularly women - this demographic accounts for the majority of drug-induced hyponatremia cases 3
- Taking multiple medications that can affect sodium homeostasis (diuretics, antidepressants, drugs acting on renin-angiotensin system) 3
- On concurrent medications from the 2019 AGS Beers Criteria list associated with hyponatremia/SIADH 4
Timing of Onset
The time to onset of drug-induced hyponatremia varies widely (median 79 days in one analysis), with approximately 70% occurring within the first year of treatment. 3 This means monitoring should be continuous throughout treatment, not just during initiation 3.
Management Approach
If hyponatremia develops on gabapentin:
- Discontinue the suspected medication - 82.9% of patients showed complete recovery after withdrawal 3
- Follow standard hyponatremia management protocols based on severity and volume status 5
- Consider switching to lamotrigine if an alternative antiepileptic is needed, as it shares gabapentin's favorable hyponatremia risk profile 2
Common Pitfall to Avoid
Do not assume gabapentin is completely safe regarding sodium balance simply because its risk is lower than other antiepileptics. 1, 2 The FDA labeling confirms hyponatremia can occur, and the Swedish study demonstrated a statistically significant association during treatment initiation 1, 2. Baseline and periodic sodium monitoring remains prudent, especially in high-risk patients 3.