Should I use Epidyolex (cannabidiol) or Ospolot (sulthiame) for epilepsy?

Comparison of Epidyolex (Cannabidiol) and Ospolot (Sulthiame) for Epilepsy

Epidyolex (cannabidiol) is recommended over Ospolot (sulthiame) for most types of drug-resistant epilepsy, particularly for Dravet Syndrome, Lennox-Gastaut Syndrome, and seizures associated with tuberous sclerosis complex, due to stronger evidence and regulatory approval. 1

Evidence Base for Each Medication

Epidyolex (Cannabidiol)

• Epidyolex is the only cannabis-derived drug that has successfully passed clinical trials and obtained both FDA and European Medicines Agency approval specifically for epilepsy treatment 1
• It has demonstrated effectiveness in randomized, placebo-controlled trials for drug-resistant epilepsy, particularly in specific syndromes like Dravet Syndrome and Lennox-Gastaut Syndrome 1
• Cannabidiol has a specific anti-seizure mechanism of action without psychoactive effects 1

Ospolot (Sulthiame)

• Sulthiame has been used primarily for psychomotor seizures, focal seizures, and grand mal seizures, usually in conjunction with other anticonvulsants 2
• It has shown particular effectiveness in juvenile myoclonic epilepsy and may be useful as an adjunct therapy in Lennox-Gastaut syndrome 2
• Recent retrospective studies show some efficacy in highly pharmacoresistant epilepsy cases, with 4 out of 12 patients showing improvement in seizure frequency in a 2024 study 3

Efficacy Comparison

Epidyolex Efficacy

• Demonstrated efficacy through rigorous clinical trials specifically for drug-resistant epilepsy 1
• Particularly effective for Dravet Syndrome, Lennox-Gastaut Syndrome, and seizures associated with tuberous sclerosis complex 1

Sulthiame Efficacy

• In a study of 28 patients with intractable epilepsy, only 2 patients (7%) became seizure-free, while 8 patients (29%) showed >50% seizure reduction 4
• Six out of 10 patients who initially responded positively developed tolerance within 2-5 months 4
• More recent data shows potential efficacy in reducing spike-wave index during sleep in patients with epileptic encephalopathy 3

Safety Profile

Epidyolex Safety

• Meta-analysis shows increased risk of adverse events compared to placebo (risk ratio 1.12 for any grade AEs, 3.39 for severe grade AEs) 5
• Higher risk of serious adverse events (RR 2.67), events leading to discontinuation (RR 3.95), and events requiring dose reduction (RR 9.87) 5

Sulthiame Safety

• Generally well-tolerated with reported side effects including enuresis, drowsiness, and drooling 4
• In studies, side effects were typically not severe enough to cause treatment discontinuation 4
• Some patients may experience somnolence/drowsiness, aggression, or increased seizure frequency 3

Clinical Decision Algorithm

1. First-line consideration:

   • For Dravet Syndrome, Lennox-Gastaut Syndrome, or tuberous sclerosis complex: Consider Epidyolex first 1
   • For juvenile myoclonic epilepsy: Consider Sulthiame as a potential option 2

2. Second-line or adjunctive therapy:

   • If first-line treatments (carbamazepine, phenytoin, valproic acid) fail, consider Epidyolex before Sulthiame due to stronger evidence base 6, 1
   • Consider Sulthiame as an adjunctive therapy in cases of Lennox-Gastaut syndrome or epileptic encephalopathies with spike-wave activation in sleep 2, 3

3. Special considerations:

   • For patients with genetic epilepsies: Sulthiame may be particularly effective in patients with specific genetic variants (e.g., NDUFS1 and SATB1) 3
   • For patients concerned about adverse events: Discuss the higher documented risk of adverse events with Epidyolex 5

Common Pitfalls and Considerations

• Be aware that 6 out of 10 patients who initially respond to Sulthiame may develop tolerance within 2-5 months 4
• Monitor for adverse events with Epidyolex, as it has a documented higher risk of serious adverse events compared to placebo 5
• Consider that the evidence base for Epidyolex is stronger and more recent than for Sulthiame 1, 4
• Remember that both medications are typically used as add-on therapy in drug-resistant epilepsy rather than first-line monotherapy 1, 4
• For refractory status epilepticus, neither medication is recommended as first or second-line therapy; benzodiazepines followed by valproate, phenytoin/fosphenytoin, or levetiracetam are preferred 7, 8