Proposed dose equivalence between clonazepam and pramipexole in patients with restless legs syndrome

Abstract Background Dopamine agonists are accepted as the first-line medications for restless legs syndrome (RLS). In some Asian countries, clonazepam is one of the prevalent medications for RLS because of its effect on sleep disturbances. To date, there have not been any studies that examined equivalent doses of pramipexole and clonazepam. To evaluate equivalent doses of pramipexole and clonazepam in RLS, we investigated the efficacy and tolerability after conversion from clonazepam to pramipexole, and examined dose equivalence between the two prescriptions. Methods In a prospective, open-label, multicenter study, 26 RLS patients treated with clonazepam (mean age: 69.2 ± 11.0 years old) were enrolled and then rapidly switched to pramipexole using a conversion calculation of 4:1 for daily doses. Then the daily dose of pramipexole was up titrated or tapered by 0.125 mg/day at each subsequent examination. RLS symptoms and daytime somnolence were evaluated using the International RLS Study Group rating scale (IRLS), Clinical Global Impressions — Severity of illness (CGI-S) and the Epworth Sleepiness Scale (ESS), respectively. Results Conversion from clonazepam to pramipexole resulted in significant reductions of IRLS (16.3 ± 8.7 to 9.1 ± 6.3) and ESS (6.5 ± 4.2 to 4.4 ± 3.2). CGI scores demonstrated improvement after conversion. In 4 patients (15%), adverse events such as somnolence, sensation of oppression in the lower limbs, diarrhea, or nausea were present. Correlation analysis demonstrated a significant relationship between these daily doses. Spearman's correlation coefficient was 0.662. Our study, however, has some limitations since it is an open-label trial and includes only 26 patients. Further studies using a double-blind design or a crossover design are recommended. Conclusions Statistical analysis demonstrated a 4:1 conversion for clonazepam to pramipexole. When switchover from clonazepam to pramipexole is done, this conversion ratio may be helpful to determine the initial dose of pramipexole for treating RLS.