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Restless Legs Syndrome (RLS) is a sensory-motor neurological disorder which is associated with sleep disturbance and emotional distress. Low dose opioid medications are prescribed for treatment-refractory RLS. We now report two-year longitudinal data from the National RLS Opioid Registry, a national sample of patients using opioids for RLS. Methods Individuals (n=500) taking a prescribed opioid for diagnosed RLS were enrolled in the registry from 12/2017–9/2019. Information on initial and current opioid dosages, side effects, past and current RLS treatments, and RLS severity was collected by interview at baseline. Follow-up online surveys were performed at six-month intervals for two years. Results At the time of analysis, 325 participants had reached two years since enrollment and completed the two-year survey (retention rate=95.3%). There were no mean changes from baseline in RLS symptom severity, sleep, or mood measures. Opioid dose changes from baseline to one- and two-year follow-up were: unchanged (51.2%, 43.1%), increased dose (29.7%, 36.7%), decreased dose (19.1%, 20.2%). Only 7.9% of participants increased dose from baseline at both one and two years. The median dose increase from baseline to two-years was just 10 morphine milligram equivalents (MME). Dose increases of &amp;gt;25 MME occurred in 7.3% of participants (vs 5.2% at one-year) and were independently associated with use of an opioid for a comorbid pain condition in addition to RLS (OR 5.91, p=0.02), discontinuing a non-opioid RLS medication (OR 4.26, p=0.01), and age of 55 or younger at baseline (OR 3.60, p=0.01). Being on an opioid medication for &amp;lt;1 year at baseline was a predictor at one-year follow-up but not during year two of participation. Conclusion Prescribed opioid doses remained relatively stable over the two years following enrollment into the registry. Of the 37% of participants that increased dose, over half increased by 10 MME or less. Individuals at the start of opioid treatment for RLS do not see elevated rates of dose increase past the first year of use. Future longitudinal data will improve our understanding of the efficacy and tolerability of opioids for RLS. Support (if any) The RLS Foundation, Baszucki Brain Research Fund, Florence Petrlik Family Foundation, Diane and Richard Brainerd, and Steven Silin

532 Two-Year Longitudinal Data From the National Restless Legs Syndrome Opioid Registry