Sodium Oxybate Improves Voice Symptoms in Patients with Alcohol-Responsive LD

by Linda Kossoff •

CLINICAL QUESTION

What is the efficacy and safety of sodium oxybate versus placebo in patients with isolated laryngeal dystonia (LD)?

BOTTOM LINE

Sodium oxybate provides clinically meaningful improvement of voice symptoms in patients with alcohol-responsive (EtOH+) LD, without a rebound and with acceptable tolerability.

BACKGROUND: Laryngeal dystonia causes involuntary spasms in laryngeal muscles used during speaking. Symptoms of LD are managed with botulinum neurotoxin (BoNT) injections, but many patients do not benefit, and off-label oral medications provide mild to no benefits. Advances in understanding dystonia symptomology and pathophysiology open the door to novel drugs for LD.

STUDY DESIGN: Phase IIb clinical trial

SETTING: Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear and Harvard Medical School, Boston

SYNOPSIS: Researchers recruited 106 patients (74 females; mean age 58.6 years) with EtOH+ and alcohol-non-responsive (EtOH–) LD, 53 of whom had isolated focal LD, and 53 of whom had co-occurring dystonic tremor of voice. Of those recruited, 92 patients received BoNT injections an average of 39.0 months prior to participation. All patients underwent baseline assessments and completed a self-evaluation of voice and speech symptom severity. Patients were randomly assigned to receive sodium oxybate (1.5 g) in treatment period 1, followed by placebo in period 2; or placebo in treatment period 1, followed by sodium oxybate in period 2. The study was conducted during three visits on three consecutive days. The primary outcome was a change from baseline in LD symptom severity 40 minutes after drug intake. Results showed that compared to baseline, patients with EtOH+ but not EtOH– had a statistically significant improvement (>16%) in LD symptoms at 40 minutes following sodium oxybate versus placebo, with an average of 40.81% drug benefits. Drug efficacy waned by 300 minutes after intake without a rebound. No changes were found in cognitive function, suicidality, or vital signs. Adverse effects included mild dizziness, nausea, and daytime sleepiness. Study limitations included a single-center trial.

CITATION: Simonyan K, et al. Efficacy and safety of sodium oxybate in isolated focal laryngeal dystonia: a phase IIb double-blind placebo-controlled cross-over randomized clinical trial. Ann Neurol. 2024. doi: 10.1002/ana.27121.