Can Gabapentin Cause SIADH?
Gabapentin is not established as a cause of SIADH based on current guideline evidence, though structurally related pregabalin has rare case reports of SIADH. The major guidelines on SIADH do not list gabapentin among the well-documented medication causes of this syndrome.
Evidence from SIADH Guidelines
The comprehensive guidelines on SIADH causes identify specific high-risk medication classes but notably do not include gabapentin 1, 2:
Established medication causes of SIADH include: SSRIs, SNRIs, carbamazepine, oxcarbazepine, NSAIDs, tramadol, certain antipsychotics, platinum-based chemotherapy (cisplatin), vinca alkaloids (vincristine, vinblastine), cyclophosphamide, and opioids 1, 2
Antiepileptic drugs specifically associated with SIADH are carbamazepine and oxcarbazepine, which have moderate to high level evidence 1
The 2019 American Geriatrics Society Beers Criteria, which comprehensively lists medications associated with SIADH in vulnerable populations, does not include gabapentin 1
Related Drug Evidence: Pregabalin
While gabapentin itself is not listed, pregabalin (a structurally related calcium channel α2-δ subunit ligand) has a single case report of SIADH 3:
A 2016 case report documented pregabalin-induced hyponatremia meeting SIADH criteria, with rapid improvement after drug discontinuation 3
However, this represents extremely rare occurrence and is not reflected in major SIADH guidelines 3
Pregabalin's known adverse effects include CNS disturbance, peripheral edema, and weight gain, but hyponatremia is rarely reported 3
Clinical Context for Gabapentin Use
Gabapentin is used for neuropathic pain in diabetic neuropathy and has shown efficacy, though it is not FDA-approved for this specific indication 4:
Common adverse effects in older patients may be more severe and can be attenuated by lower starting doses and gradual titration 4
The drug is generally considered to have a favorable safety profile compared to other neuropathic pain medications 4
Critical Clinical Pitfalls
If hyponatremia develops in a patient taking gabapentin, consider these more likely culprits first:
Concurrent medications with established SIADH risk: SSRIs, carbamazepine, NSAIDs, or thiazide diuretics, especially in combination 1, 5
Polypharmacy risk: The concurrent use of multiple CNS agents increases SIADH risk substantially 1
Thiazide-SSRI combination: This pairing substantially increases hyponatremia risk and is particularly dangerous 1
Elderly patients: Aging increases sensitivity to hyponatremia due to reduced glomerular filtration rate 1
Alternative diagnoses: Malignancy (especially small cell lung cancer), CNS disorders, pulmonary infections, or cerebral salt wasting in neurosurgical patients 2, 6
Monitoring Recommendations
If gabapentin is suspected (despite lack of guideline evidence):
Check serum sodium, plasma osmolality, urine osmolality, and urine sodium to confirm SIADH diagnosis (serum sodium <134 mEq/L, plasma osmolality <275 mosm/kg, urine osmolality >500 mosm/kg, urine sodium >20 mEq/L) 1
Exclude hypothyroidism and adrenal insufficiency before diagnosing SIADH 1, 2
Serum uric acid <4 mg/dL has 73-100% positive predictive value for SIADH 2
Discontinue the suspected medication and observe for improvement, as drug-induced SIADH typically resolves after cessation 5, 7