Sodium oxybate for excessive daytime sleepiness in narcolepsy: a systematic review and meta-analysis of randomized placebo-controlled trials.

BACKGROUND &

OBJECTIVES

Excessive daytime sleepiness (EDS) is a debilitating symptom in narcolepsy. Sodium oxybate (SO) is approved for narcolepsy and has shown consistent efficacy across multiple formulations. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of SO compared to placebo in reducing EDS in patients with narcolepsy.

METHODS

A systematic search was conducted in PubMed, Cochrane Library, and ClinicalTrials.gov from inception to March 2024. Randomized, double-blind, placebo-controlled trials of SO in narcolepsy reporting Epworth Sleepiness Scale (ESS) scores were included. Primary outcome was change in ESS from baseline. Mean difference (MD) with 95% confidence intervals (CI) was pooled using a random-effects model. Heterogeneity was assessed using I² statistic. Subgroup analyses were performed by formulation and dose. Risk of bias was assessed using Cochrane RoB 2.0 tool. The review followed PRISMA guidelines and was registered with PROSPERO (CRD42024604014).

RESULTS

Five randomized controlled trials (n = 1,066 patients) met inclusion criteria. SO significantly reduced ESS scores compared to placebo (pooled MD: -4.8 points; 95% CI: -5.8 to -3.8; P < 0.001; I²=44%). Subgroup analysis showed comparable effects across formulations: once-nightly extended-release FT218 (MD: -4.9; 95% CI: -6.2 to -3.6), low-sodium oxybate JZP-258 (MD: -4.7; 95% CI: -5.8 to -3.6), and standard twice-nightly (MD: -4.7; 95% CI: -5.7 to -3.7). Objective sleep latency improved by 3.5 min. Cataplexy frequency reduced by 3.3 attacks/week (P < 0.001). Safety outcomes included mild-to-moderate adverse events (nausea 9-18%, dizziness 8-11%, headache 7-11%), with discontinuation rates of 3-11%.

INTERPRETATION &

CONCLUSIONS

Sodium oxybate significantly reduces EDS in narcolepsy with consistent effects across formulations. Once-nightly and low-sodium formulations offer additional benefits in terms of dosing convenience and reduced sodium burden. Safety profiles were acceptable, with mild-to-moderate adverse events being most common. Larger trials with longer durations are warranted for validation.

REGISTRATION: PROSPERO (CRD42024604014).