Proposed dose equivalence between clonazepam and pramipexole in patients with restless legs syndrome.
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+/-11.0years 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 0.125mg/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.
Shinno
Hideto
H
Department of Neuropsychiatry, Kagawa University School of Medicine, 1750-1 Ikenobe, Miki, Kida, Kagawa 761-0793, Japan. shinnoh@med.kagawa-u.ac.jp
Oka
Yasunori
Y
Otsuki
Manabu
M
Tsuchiya
Satoshi
S
Mizuno
Soichi
S
Kawada
Seiichi
S
Innami
Toshihiko
T
Sasaki
Akira
A
Hineno
Takashi
T
Sakamoto
Tetsuro
T
Inami
Yasushi
Y
Nakamura
Yu
Y
Horiguchi
Jun
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants / Q000627:therapeutic use*; D052160:Benzothiazoles / Q000494:pharmacology*; D002998:Clonazepam / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D018757:GABA Modulators / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077487:Pramipexole; D011446:Prospective Studies; D012148:Restless Legs Syndrome / Q000188:drug therapy*; D012720:Severity of Illness Index
D000975:Antioxidants; D052160:Benzothiazoles; D018757:GABA Modulators; D002998:Clonazepam; D000077487:Pramipexole