Can Phenytoin (Eptoin) Be Used in SIADH?
Phenytoin is generally ineffective for treating SIADH and should not be used as a therapeutic option. While historically proposed as a treatment, clinical evidence demonstrates poor efficacy, particularly for long-term management.
Evidence Against Phenytoin Use
A prospective study of seven consecutive patients with SIADH of neurological origin who failed water restriction found that only one patient responded to chronic phenytoin therapy, and this patient had suffered a basal skull fracture—a specific clinical scenario that may not generalize to other SIADH etiologies 1.
The same study concluded that in the majority of cases of SIADH of neurological origin, phenytoin is ineffective on a long-term basis 1.
Although phenytoin has been mentioned in older literature as a potential treatment option, there are few data to support its use, and it is not included in current evidence-based treatment algorithms 2.
Recommended Treatment Approaches for SIADH
Acute Symptomatic SIADH (Severe Symptoms)
Administer 3% hypertonic saline with a goal to correct 6 mmol/L over 6 hours or until severe symptoms resolve, with ICU monitoring and serum sodium checks every 2 hours initially 3.
Total correction must not exceed 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome 4, 3.
Mild to Moderate SIADH (Asymptomatic or Mild Symptoms)
Fluid restriction to 1 L/day is the cornerstone of first-line treatment for chronic SIADH 4, 3.
If fluid restriction fails or is poorly tolerated, second-line options include oral urea or demeclocycline 3, 2, 5.
Vasopressin receptor antagonists (vaptans such as tolvaptan) are effective specific therapies for SIADH, with a starting dose of 15 mg once daily 3, 6.
Treatment of Underlying Cause
Discontinue offending medications such as carbamazepine, SSRIs, chlorpropamide, cyclophosphamide, and vincristine 3.
Treat the underlying malignancy in cases of paraneoplastic SIADH, as effective cancer treatment often resolves the syndrome 3.
Common Pitfalls to Avoid
Do not use phenytoin as a treatment option for SIADH, as clinical evidence demonstrates lack of efficacy 1.
Avoid overly rapid correction (>8 mmol/L in 24 hours) to prevent osmotic demyelination syndrome 4, 3.
Do not confuse SIADH with cerebral salt wasting (CSW) in neurosurgical patients, as CSW requires volume and sodium replacement rather than fluid restriction 4, 3.