Background and purpose: To measure the effect of the nocturnal administration of sodium oxybate on cataplexy in patients with narcolepsy.
Patients and methods: This trial was conducted with 228 adult narcolepsy/cataplexy patients in 42 sleep clinics. Patients using anticataplectic medications were weaned from these medications, then randomized to receive 4.5, 6 or 9 g sodium oxybate nightly or placebo for 8 weeks. Patients receiving 6 and 9 g doses were titrated to their final dose in weekly 1.5 g increments. Placebo patients underwent a randomized mock dose-titration schedule. The effect of sodium oxybate on weekly cataplexy attacks was measured using patient daily diaries.
Results: Compared to placebo, nightly doses of 4.5, 6 and 9 g sodium oxybate for 8 weeks resulted in statistically significant median decreases in weekly cataplexy attacks of 57.0, 65.0 and 84.7%, respectively. The decrease in cataplexy at the 4.5 g dose represents a novel finding. The weekly increase in sodium oxybate dose was associated with fewer adverse events than previously reported in double-blind sodium oxybate trials using fixed doses. Some adverse events reported demonstrated a clear dose-response relationship.
Conclusions: In the largest study of its kind, sodium oxybate was highly effective for the treatment of cataplexy. The improvements in cataplexy are dependent on the dosage of sodium oxybate as well on the duration of treatment. Weekly dose titration appears to be well-tolerated.