Baseline and 1-year longitudinal data from the National Restless Legs Syndrome Opioid Registry.

STUDY OBJECTIVES: Restless legs syndrome (RLS) is a sensory-motor neurological disorder. Low dose opioid medications are prescribed for treatment-refractory RLS. We describe baseline and 1-year longitudinal dosing and symptom outcomes for the National RLS Opioid Registry. METHODS: Individuals currently taking a prescribed opioid for diagnosed RLS are included in the registry. Information on initial and current opioid dosages, side effects, past and current concomitant RLS treatments, RLS severity, psychiatric history, and opioid abuse risk factors were collected at baseline. Follow-up online surveys were performed at 6 months and 1-year. RESULTS: Participants (n = 500) are primarily white, elderly, educated, and retired. Half of all subjects are on opioid monotherapy. Nearly 50% of all subjects are taking methadone, and one-quarter are taking oxycodone formulations. The median total daily opioid dose is 30.0 morphine milligram equivalents (MME). At baseline, three-quarters of registry participants had been taking a prescribed opioid for RLS for more than 1 year and one-third for more than 5 years, and had mild-moderate RLS symptoms. At 1-year follow-up, 31.2% increased dose (median = 10 MME) and 16.0% decreased dose of their opioid. An MME increase ≥25 was associated with: opioid use for non-RLS pain, <1 year of opioid use, opioid switch to methadone, and discontinuation of non-opioid RLS medications which, combined, accounted for 91.7% of those with 1-year follow-up increases ≥25 MME. CONCLUSIONS: In refractory RLS, prescribed opioids are generally used at low doses with good efficacy. Longitudinally over 1 year, roughly one-third of participants increased their prescribed opioid dose, though generally by small amounts, with larger dose increases accounted for by predictable features.

Topiramate reduces nocturnal eating in sleep-related eating disorder.

STUDY OBJECTIVES: Sleep-related eating disorder (SRED) is a parasomnia characterized by partial arousals from sleep with compulsive consumption of food with impaired level of awareness and memory for the event. Small case series' have demonstrated efficacy of topiramate in SRED. We conducted a placebo-controlled randomized clinical trial of topiramate to assess efficacy in SRED. METHODS: Thirty-four participants with an ICSD-2/ICSD-3 diagnosis of SRED with >6 months of symptoms and ≥3 sleep-related eating episodes per week were randomized to placebo or topiramate with flexible dosing to a maximum dosage of 300 mg for 13 weeks. Primary outcomes were percentage of nights with eating and Clinician Global Impression-Improvement (CGI-I). Intention-to-treat last observation carried forward (ITT LOCF) analysis was conducted. RESULTS: Mean age was 39.5 years, 74% were female, with mean duration of sleep-related eating of 13.7 years. SRED symptoms were significantly reduced with topiramate (74.7% to 33.2% nights/week; n = 15) compared to placebo (77.0% to 57.4%; n = 17) (p = 0.035). There were significantly more CGI-I responders on topiramate (71%) than placebo (27%) (p = 0.016). Level of wakefulness (r = -0.49) and memory for nighttime eating (r = -0.58) at baseline predicted topiramate response. The topiramate group lost significantly more weight than the placebo group (-8.5 lbs vs. +1.0 lbs, p = 0.001). The most common side effects were paresthesias and cognitive dysfunction. CONCLUSIONS: This first randomized controlled trial demonstrating efficacy for treatment of SRED supports preliminary data on the use of topiramate for SRED. Side effects were prominent for topiramate. Limitations include a small sample size and a high drop-out rate in both study groups. CLINICAL TRIAL INFORMATION: NCT00606411.

Opioid-galanin receptor heteromers mediate the dopaminergic effects of opioids.

Identifying non-addictive opioid medications is a high priority in medical sciences, but µ-opioid receptors mediate both the analgesic and addictive effects of opioids. We found a significant pharmacodynamic difference between morphine and methadone that is determined entirely by heteromerization of µ-opioid receptors with galanin Gal1 receptors, rendering a profound decrease in the potency of methadone. This was explained by methadone's weaker proficiency to activate the dopaminergic system as compared to morphine and predicted a dissociation of therapeutic versus euphoric effects of methadone, which was corroborated by a significantly lower incidence of self-report of "high" in methadone-maintained patients. These results suggest that µ-opioid-Gal1 receptor heteromers mediate the dopaminergic effects of opioids that may lead to a lower addictive liability of opioids with selective low potency for the µ-opioid-Gal1 receptor heteromer, exemplified by methadone.