Buprenorphine Shows Promise in Management of Severe Restless Leg Syndrome

Long-term administration of buprenorphine reduced RLS symptom burden and facilitated the elimination of dopamine agonists in patients with augmentation.

Buprenorphine lessens restless leg syndrome (RLS) symptom burden and bridges treatment in individuals with augmentation discontinuing dopamine agonists. These are the results of a study presented at the 2023 Annual Meeting of the American Academy of Sleep Medicine and the Sleep Research Society, held from June 3 to 7 in Indianapolis, Indiana.

In patients with moderate-to-severe RLS symptoms, opioid medications are the preferred second line treatment. Buprenorphine, a partial opioid agonist at mu-opioid receptors, is preferred due to its lower risks for respiratory depression and dependence. Researchers hypothesized that buprenorphine is well-tolerated for long-term administration and may also attenuate weaning off of dopamine agonists in those with augmentation, or worsening of RLS symptoms after dopamine agonists initiation.

The researchers conducted a retrospective, longitudinal cohort study over a 21-month period by a tertiary RLS specialist. Patient outcomes were measured through a combination of electronic health record-based questionnaires as well as clinician interview.

The primary outcome was International RLS Study Group (IRLS-SG), with additional questionnaires comprised of: Clinical Global Impressions of Improvement (CGI-I), Epworth Sleepiness Scale (ESS), Insomnia Severity Index (ISI), Patient Health Questionnaire (PHQ-9), and Patient-Reported Outcomes Measurement Information System-Sleep Disturbance domain (PROMIS-SD).

[O]ur findings show buprenorphine markedly reduced RLS symptoms, effectively enabled the elimination of dopamine agonists in patients with augmentation …

The researchers used a linear mixed model to assess change from baseline to 6-week, 3-month, 6-month, and 1-year intervals, adjusting for age, sex, RLS medications at visit, and iron infusion.

In total, 55 patients (56.4% women, 64.9±12.1 years) were started on buprenorphine for RLS, that of which 42 (76.3%) continued on medication until the study concluded.

IRLS-SG reduced at every follow-up interval from baseline 27.8 (95% CI, 25.3-30.3) to year 1 (11.4; 95% CI, 7.4-15.4] at year 1, P trend <0.001).

From the 39 (70.9%) patients who had augmentation with dopamine agonists at baseline, 32 (82.1%) discontinued the medication and 5 (12.8%) had a reduced dose at final visit.

A statistically significant longitudinal trend was found at 1 year improvement in:

  • ESS: 9.9 (95% CI, 8.0-11.8) to 6.9 (95% CI, 4.5-9.4); P =.003;
  • ISI: 18.0 (95% CI ,15.9-20.1) to 15.0 (95% CI, 11.6-18.3); P =.048;
  • PHQ-9: 10.4 (95% CI, 8.2-12.5) to 6.1 (95% CI, 3.6-8.6); P <.001, and
  • PROMIS-SD: 63.0 (95% CI, 60.2-65.7) to 53.8 (95% CI, 49.8-57.8); P <.001.

Discontinuation of medication occurred in 13 (23.6%) patients due to side effects, including dizziness (most common), nausea, and cognitive complaints.

The researchers concluded, “our findings show buprenorphine markedly reduced RLS symptoms, effectively enabled the elimination of dopamine agonists in patients with augmentation, improved sleep and other health quality measures, and was tolerated comparably to other RLS medications.”


Berkowski J, Wang L, Mehra R. Longitudinal assessment of buprenorphine effectiveness for severe restless legs syndrome and dopaminergic augmentation. Abstract presented at: SLEEP 2023; June 3-7, 2023; Indianapolis, IN. Abstract 0699.