0663 Buprenorphine/naloxone Treatment Of Refractory RLS

Abstract

Introduction: Schedule II opioids are often the final medication class prescribed for refractory RLS,but use is limited by concerns over tolerance,dependence,respiratory depression,prescription monitoring and dispensing. Buprenorphine (B) is a Schedule III partial mu-opioid receptor agonist,with a 24-48 hr half-life,often formulated with the antagonist naloxone (N) to manage opioid dependence. We report our open label experience with B/N. Methods: Seven subjects (5 men) were prescribed B/N. Average age was 68 ± 2.5 (SD),BMI 31.3 (± 7.7),and RLS disease duration 30.7 ± 18.9 yrs. Over their 10.7 ± 7.5 yr treatment courses,9.3 ± 1.1 medications (2.4 ± 0.5 of which were opioids) had been tried,and 3 had received iv iron. Dopamine agonist therapy was limited by augmentation (N=6) and impulse control disorders (N=3). OSA was mild (N=2),moderate (N=2),or severe (N=3). Mobilizable iron stores were normal in six. Results: Treatment inadequacy contributed to loss of employment (N=2),diminished work productivity (N=3),CPAP non-adherence (N=3 of 4),and MVAs (N=2). Opioid therapy was limited by insomnia (N=2),sleepiness (N=2),anxiety (N=2),pruritis (N=1),lack of efficacy (N=1),or waning in dose duration benefit (N=3) manifesting as “withdrawal myoclonus”/ waking periodic leg movements (PLM) (N=2). After discontinuing opioids,2.0/0.5mg sublingual B/N was prescribed each twelve hours (N=1),or each evening (N=6) concurrent with other RLS medications. One subject discontinued B/N secondary to anxiety/ insomnia.RLS symptoms and signs (i.e.,PLM) were promptly eliminated in two subjects. Dizziness/sleepiness/gait instability necessitated discontinuation or ongoing downwards dose titration. Four subjects (2 retirees) realized a profound,immediate benefit free of AEs for 2-6 months. IRLSSG rating scale severity decreased from 31.3 ± 6.7 to 4 ± 8 and insomnia severity index from 19.8 ± 6.1 to 1.3 ± 1.9. CPAP usage ≥ 4 hr/night increased from 39 to 68%,and 72 to 82%,and by 65 and 45 min/night,respectively, in two subjects). Employment (N=1) and premorbid work productivity (N=1) were regained. Conclusion: Sleep,CPAP adherence,and quality of life in chronic RLS patients experiencing augmentation,treatment refractoriness, or side effects with traditional opioids,can benefit from B/N. Incorporation into treatment algorithms warrants further investigation given B/Ns unique pharmacology and DEA schedule status.