Role of Vigabatrin
- Indication:
- Approved treatment for infantile spasms, especially in TS-associated IS.
Challenges in Studying Medications for IS
- Inhibits GABA-transaminase, increasing GABA levels in the brain.
Proven Treatments for IS
-
Adrenocorticotropic Hormone (ACTH):
- One of the most commonly used therapies for IS.
- Exact mechanism unclear but hypothesized to involve the brain-adrenal axis:
- Downregulates excessive corticotropin-releasing hormone (CRH) expression in the brain.
- CRH overexpression may cause spasms in IS.
- Delivered via injection, which adds complexity to its use.
-
Vigabatrin:
- Approved in the US for IS treatment (available in the UK and Ireland since 1989).
- Mechanism of Action:
- Suicide substrate inhibiting gamma-aminobutyric acid-transaminase (GABA-T).
- Inhibits the breakdown of GABA → Increases GABA concentrations in the brain → Suppresses seizures.
- Pharmacological Advantages:
- Does not strongly induce or inhibit hepatic enzymes.
- Virtually unbound to serum protein → Minimal drug interactions.
- Can be taken without regard to meals.
- High solubility → Achieves bioavailability up to 70%.
- Reported Drug Interaction:
- May decrease phenytoin levels without leading to breakthrough seizures.
Insufficient Evidence for Other Medications
- Effective in controlling spasms and normalizing EEG in many cases.
- Particularly beneficial in symptomatic IS with tuberous sclerosis.
Comparison of ACTH and Vigabatrin
- Risk of visual field defects with long-term use.
- Requires regular ophthalmologic monitoring.
Clinical Trials Overview
1. Vigevano et al. (Original Comparative Study with ACTH)
- Should be considered in cases of treatment-resistant IS.
- Often used alongside ACTH or corticosteroids for synergistic effects.