Sodium oxybate for narcolepsy with cataplexy: systematic review and meta-analysis

Abstract

Study objectives: To assess the efficacy and safety of sodium oxybate (SXB) in narcolepsy-cataplexy patients.

Design: Systematic review and meta-analysis.

Patients: Adults with narcolepsy-cataplexy.

Interventions: SXB.

Measurements and results: Electronic databases (e.g., MEDLINE) and references of included studies were searched to identify randomized controlled trials (RCTs) assessing the efficacy and safety of SXB for patients with narcolepsy-cataplexy. Risk of bias was appraised using the Cochrane risk of bias tool. Meta-analysis was conducted in Review Manager Version 5. Six RCTs and 5 companion reports were included after screening 14 full-text articles and 483 citations. All were private-industry funded. SXB (usually 9 g/night) was superior to placebo for reducing mean weekly cataplexy attacks (n = 2 RCTs, mean difference [MD]: -8.5, 95% CI: -15.3, -1.6), increasing maintenance wakefulness test (MWT) (n = 2, MD: 5.18, 95% CI: 2.59-7.78), reducing sleep attacks (n = 2, MD: -9.65, 95% CI: -17.72, -1.59), and increasing Clinical Global Impression scores (n = 3, relative risk, RR: 2.42, 95% CI: 1.77-3.32). SXB did not significantly increase REM sleep versus placebo (n = 2, MD: -0.49, 95% CI: -3.90, 2.92). Patients receiving SXB had statistically more adverse events versus placebo, including nausea (n = 3, relative risk [RR]: 7.74, 95% CI: 3.2, 19.2), vomiting (n = 2, RR: 11.8, 95% CI: 1.6, 89.4), and dizziness (n = 3, RR: 4.3, 95% CI: 1.1, 16.4). Enuresis was not significantly different from placebo (n = 2, RR: 2.6, 95% CI: 0.8, 9.8). All meta-analyses had minimal statistical heterogeneity (p-value > 0.1).

Conclusion: Narcolepsy patients on SXB have significant reductions in cataplexy and daytime sleepiness. SXB is well tolerated in patients with narcolepsy, and most adverse events were mild to moderate in severity.

Keywords: Sodium oxybate; Xyrem; cataplexy; meta-analysis; narcolepsy; randomized controlled trial; systematic review.

Figures

Figure 1. Study flow

Figure 2. Mean weekly cataplexy attacks meta-analysis

Figure 3. Maintenance of wakefulness test meta-analysis

Figure 4. Mean sleep attacks meta-analysis

Figure 5. Proportion of patients “much improved” or “very much improved” on the Clinical Global Impression of Change versus all other categories meta-analysis

Figure 6. Polysomnographic data for nocturnal sleep meta-analysis (REM)

Figure 7. Adverse events: gastrointestinal/nausea

Figure 8. Adverse events: vomiting

Figure 9. Adverse events: dizziness

Figure 10. Adverse events: enuresis