One-year treatment with standard and sustained-release levodopa: appropriate long-term treatment of restless legs syndrome?
To investigate the long-term efficacy and safety of sustained-release (SR) in combination with regular-release (RR) levodopa/benserazide in the treatment of restless legs syndrome (RLS), an open-label, prospective, extension study of a preceding double-blind crossover trial was performed for 12 months. Twenty-three severely disturbed RLS patients (7 men, 16 women) received a combination of RR and SR levodopa. Patients were treated on average for 10 months with a mean daily dose of 203 +/- 101 mg of RR and of 185 +/- 93 mg of SR levodopa. The mean daily total dose was 388 +/- 162 mg levodopa. Efficacy was documented using patient's rating scales, sleep diaries, and investigator's global ratings with the Clinical Global Impressions (CGI). Ten of 23 patients completed the 1-year extension. Between baseline of the crossover trial and endpoint of the extension study (last-observation-carried-forward method, intention-to-treat population), quality of sleep improved (+3.5 +/- 1.9, 7-point scale), sleep latency was shortened (-131 +/- 152 minutes), and total sleep time lengthened (+ 190 +/- 136 minutes). Severity of RLS at time of falling asleep (-6.5 +/- 3.4, 11-point scale) and during the night (-6.0 +/- 3.5) was markedly lower at the end of the extension but severity of RLS during the day (+1.9 +/- 5.0) slightly increased. Of 13 dropouts, 8 patients discontinued therapy because of worsening RLS during the day. This trial shows that long-term treatment with the combination of RR and SR levodopa/benserazide in RLS patients with late-night problems was efficacious and not limited by tolerability problems in 40% of patients, whereas in the majority of patients, aggravating daytime problems required termination of the levodopa therapy within the 1-year treatment period.
Trenkwalder
Claudia
C
Max Planck Institute of Psychiatry, Munich, Germany. ctrenkw@gwdg.de
Collado Seidel
Victor
V
Kazenwadel
Jörg
J
Wetter
Thomas C
TC
Oertel
Wolfgang
W
Selzer
Roland
R
Kohnen
Ralf
R
D000328:Adult; D000368:Aged; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001545:Benserazide / Q000627:therapeutic use; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004341:Drug Evaluation / Q000379:methods*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007980:Levodopa / Q000009:adverse effects / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination; D011446:Prospective Studies; D011788:Quality of Life; D012148:Restless Legs Syndrome / Q000188:drug therapy*; D012720:Severity of Illness Index; D016037:Single-Blind Method; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
D000978:Antiparkinson Agents; D003692:Delayed-Action Preparations; D007980:Levodopa; D001545:Benserazide