Does Spironolactone Lower Seizure Threshold?
No, spironolactone does not lower seizure threshold and may actually enhance the anticonvulsant effects of certain antiepileptic drugs in experimental models. 1, 2
Evidence from Experimental Studies
The available research directly addressing this question comes from animal models of epilepsy:
Spironolactone at doses up to 50 mg/kg did not affect any seizure parameters in amygdala-kindled rats, indicating it does not provoke seizures or lower seizure threshold when used alone 2
When combined with carbamazepine at subtherapeutic doses (15 mg/kg spironolactone + 50 mg/kg carbamazepine), spironolactone significantly reduced seizure duration and afterdischarge duration, suggesting a potential protective rather than proconvulsant effect 1
Spironolactone did not affect the anticonvulsant action of phenobarbital, clonazepam, or valproate in kindled seizure models, indicating no interference with standard antiepileptic medications 2
Clinical Context and Safety Profile
From comprehensive drug safety literature:
Spironolactone is not listed among medications known to lower seizure threshold or provoke epileptic seizures in systematic reviews of drug-induced seizures 3, 4
The drugs most commonly associated with lowering seizure threshold include antidepressants (particularly maprotiline and clomipramine), antipsychotics (chlorpromazine and clozapine), and certain antibiotics and immunosuppressants 3, 4
Common side effects of spironolactone include headache, fatigue, gynecomastia, decreased libido, and menstrual disruption—but not seizures 5
Monitoring Considerations
While spironolactone does not lower seizure threshold, standard safety monitoring remains essential:
Check serum potassium and creatinine at baseline, 1 week, 4 weeks, then at 1,2,3, and 6 months, and every 6 months thereafter 5
Hyperkalemia poses the primary safety concern, particularly in elderly patients, those with diabetes, kidney disorders, or liver disease 5
If potassium rises to >5.5 mmol/L, halve the dose; if ≥6.0 mmol/L, stop immediately 5
Clinical Bottom Line
Spironolactone can be safely used in patients with epilepsy or those at risk for seizures without concern for lowering seizure threshold. 2 The experimental evidence suggests it may even have mild anticonvulsant properties when combined with certain antiepileptic drugs, though this has not been studied in humans. Standard monitoring for hyperkalemia and renal function remains the primary safety consideration, not seizure risk.