Tetracosactide Does Not Induce Epilepsy—It Is Used to Treat Infantile Spasms
Tetracosactide (synthetic ACTH) is not associated with inducing epilepsy; rather, it is an established treatment for infantile epileptic spasms syndrome (IESS), with response rates of 48-76% for cessation of spasms. 1, 2, 3
Clinical Context and Evidence
Tetracosactide as Treatment for Epilepsy
- Tetracosactide is specifically recommended as a diagnostic and therapeutic agent in primary adrenal insufficiency, where it is used in the synacthen stimulation test 1
- More importantly, tetracosactide is an effective treatment for infantile epileptic spasms syndrome, not a cause of seizures 2, 4, 3
- In a retrospective study of 156 patients with infantile spasms, tetracosactide IV injections achieved complete response in 25 of 52 cases (48%), with the highest response rate of 75% when used as first-line therapy 2
- A prospective analysis of two randomized controlled trials (UKISS and ICISS) showed that 76% of infants treated with tetracosactide depot were free of spasms on days 13-14, compared to 67% with prednisolone 3
Mechanism and Outcomes
- Early treatment with high-dose tetracosactide (within 1 month of onset) is associated with 100% normal cognitive outcomes in cryptogenic infantile spasms, compared to only 40% in late-treatment groups 4
- The standard regimen involves tetracosactide depot 0.5-1 mg IM on alternate days for two weeks, followed by a tapering dose of prednisolone 4, 3
- Relapse rates after tetracosactide treatment are approximately 20%, which is higher than vigabatrin (5%) but still acceptable given the superior initial response rates 2
Important Distinction: Seizures in Adrenal Insufficiency
- The only connection between tetracosactide's indication (adrenal insufficiency) and seizures is that untreated primary adrenal insufficiency in children can cause hypoglycemic seizures due to cortisol deficiency 1
- This represents a complication of the underlying disease, not an effect of tetracosactide treatment 1
Comparative Efficacy
- Indirect treatment comparisons suggest that repository corticotropin injection (natural ACTH) may have five to eight times greater odds of achieving efficacy outcomes compared to synthetic tetracosactide, though both remain effective treatment options 5
- Tetracosactide shows superior response rates (48-76%) compared to oral steroids (29%) and comparable or better outcomes than vigabatrin monotherapy (30%) 2
Clinical Caveat
While antiepileptic drugs themselves can paradoxically induce seizures in certain contexts (such as carbamazepine or phenytoin provoking absences, or valproate-induced encephalopathy), this phenomenon does not apply to tetracosactide 6. Tetracosactide is a hormonal agent, not an antiepileptic drug, and its mechanism of action in treating infantile spasms likely involves modulation of corticosteroid receptors and inflammatory pathways rather than direct effects on neuronal excitability 4.