{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T09:03:47Z","timestamp":1784365427293,"version":"3.55.0"},"reference-count":37,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T00:00:00Z","timestamp":1732060800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["R01DC012545"],"award-info":[{"award-number":["R01DC012545"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To examine the efficacy and safety of sodium oxybate versus placebo in a phase IIb randomized double\u2010blind placebo\u2010controlled 2\u2010period cross\u2010over clinical trial in patients with isolated laryngeal dystonia (LD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The study was conducted from January 2018 to December 2021, pausing during the COVID\u201019\u00a0pandemic, at Massachusetts Eye and Ear in 106 patients with alcohol\u2010responsive (EtOH+) and alcohol\u2010non\u2010responsive (EtOH\u2212) LD (53 to receive 1.5g of sodium oxybate first, 53 to receive matching placebo first). The primary outcome was a change from baseline in LD symptom severity 40\u2009minutes after drug intake. Safety was based on vital signs, cognitive function, suicidality, daytime sleepiness, and adverse events. Patients, investigators, and outcome assessors were masked to study procedures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to baseline, EtOH+ but not EtOH\u2212 patients had a statistically significant improvement in LD symptoms following sodium oxybate versus placebo (EtOH+: 98.75% confidence interval [CI] =\u20090.6\u201326.9; <jats:italic>p<\/jats:italic>\u2009=\u20090.008; EtOH\u2212: 98.75% CI = \u22126.2 to 18.7; <jats:italic>p<\/jats:italic>\u2009=\u20090.42). Statistically significant minimum drug efficacy in EtOH+ patients was found at \u226516% symptom improvement (OR\u2009=\u20092.09; 98.75% CI\u2009=\u20090.75\u20135.80; <jats:italic>p<\/jats:italic>\u2009=\u20090.036), with an average of 40.81% benefits (98.75% CI\u2009=\u200934.7\u201348.6). Drug efficacy waned by 300\u2009minutes after intake without a rebound. No changes were found in cognitive function, suicidality, or vital signs. Common adverse events included mild dizziness, nausea, and daytime sleepiness.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Sodium oxybate showed clinically meaningful improvement of symptoms in EtOH+ LD patients, with acceptable tolerability. Sodium oxybate offers the first pathophysiologically relevant oral treatment for laryngeal dystonia. 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