Efficacy and safety of piribedil in early combination with L-dopa in the treatment of Parkinson's disease: a 6-month open study.
BACKGROUND
Piribedil is a non-ergot D2/D3 dopamine agonist with antagonistic effect on alpha2-adrenoceptors and lack of agonist properties at 5-HT2A/2C receptors. Previous studies indicated its efficacy in monotherapy as well as in combinatio' s disease in L-dopa-treated parkinsonian patients.


METHODS
A 6-month, open-labeled, multicenter study was conducted in Thai Parkinsonian patients who were insufficiently controlled by L-dopa (< or = 600 mg/day). Piribedil 50 mg in retard form was titrated upward to 150 mg/day (50 mg tid) by the 5th week and up to 6 months as an add-on treatment. L-dopa daily dose was kept stable until the 3rd month and could be adjusted afterwards. The main efficacy parameter was the change in UPDRS part III score versus baseline over Full Analysis Set, score variation, and percentage of responders defined by at least 30% decrease from baseline of total UPDRS part III score. The secondary efficacy criteria were changes in L-dopa dose between the third month and the end of the study, UPDRS part II score variation, Hoehn and Yahr stage variation and Schwab and England Activities of Daily Living Scale variation. The acceptability of piribedil was assessed by physical examination, weight, blood pressure and heart rate as well as the reported adverse events.


RESULTS
Twenty-nine patients (55.2% male) with the mean age of 64.0 +/- 7.2 years and mean duration of disease of 18.3 +/- 8.2 months were recruited The mean UPDRS part III score at baseline was 19.8 +/- 11.4. After 6-month treatment with piribedil, mean UPDRS part III score significantly decreased to 6.6 +/- 4.7 (p < 0.0001) with mean score variation of 13.3 +/- 10.3. Twenty-seven patients (93.1%) were responders. Mean UPDRS part II score was significantly decreased from 7.2 +/- 5.4 at baseline to 2.7 +/- 2.1 at the end of 6 months (p < 0.0001). Hoehn and Yahr stage and Schwab and England Activities of Daily Living Scale were also significantly improved Reported adverse events were mainly gastrointestinal symptoms. Blood pressure and heart rate were not significantly changed during the study period. Peak dose dyskinesia was reported only in one patient. Two patients (6.9%) were withdrawn because of adverse events.


CONCLUSIONS
Piribedil was effective on motor symptoms during a 6-month treatment in early parkinsonian patients insufficiently controlled by L-dopa and it was well tolerated.
Suwantamee
Jithanorm
J
Department of Neuro-psychiatry, Pramongkutklao Army Medical College, Bangkok 10400, Thailand.
Nidhinandana
Samart
S
Srisuwananukorn
Suwat
S
Laptikultham
Somsak
S
Pisarnpong
Apichart
A
Chankrachang
Siwaporn
S
Bundhukul
Adul
A
D000328:Adult; D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy*; D010891:Piribedil / Q000008:administration & dosage*
D000978:Antiparkinson Agents; D007980:Levodopa; D010891:Piribedil