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P2.087 The role of dopamine receptors in the induction of levodopa-induced dyskinesia in parkinsonsian rats
S112
Poster presentations / Parkinsonism and Related Disorders 15S2 (2009) S29–S199
P2.086 Efficacy and tolerability of prolonged-release Ropinirole (Requip XL) in the elderly with Parkinson’s disease S. Isaacson1 , J. Isaacson2 , D. Kreitzman3 . 1 Parkinson’s C.O.R.E. Institute of Boca Raton, 2 PREF Summer Research Program, Parkinson’s C.O.R.E. Institute of Boca Raton, Boca Raton, FL, 3 Parkinson’s Disease and Movement Disorders Center of Long Island, Commack, NY, USA Objective: Retrospective review of efficacy and tolerability of the prolonged-release ropinirole (Requip XL) in the elderly with Parkinson’s disease (PD). Background: Dopamine agonists (DA) have established efficacy in PD, but guidelines utilize age to help guide therapeutic decisionmaking. Clinical trials often have limited enrollment of elderly, so treatment is often based on anecdotal experience rather than evidence-based. Ropinirole prolonged-release provides more consistent plasma levels, so it may be less likely to cause intolerable peak dopaminergic adverse effects. Methods: projectSUNSHINE, an epidemiological multi-center longitudinal PD research database initiative, 70% of patients are over the age of seventy. projectSUNSHINE tracks extensive demographic and clinical information, at each patient encounter, including rating scales, motor fluctuations, non-motor symptoms, abd concomitant medical history. Results: Using the projectSUNSHINE database, we identified over 250 consecutive patients with PD who were treated with ropinirole prolonged-release (Requip XL). The clinical course, treatment outcome, and dosing of these ropinirole treated patients were reviewed. UPDRS II and III subscores improved, often at doses 2–8 mg. Adverse effects were mild and did not limit treatment for most patients, even those intolerant of immediate-release. Conclusion: Ropinirole prolonged-release (Requip XL) was generally well tolerated in this elderly cohort, and demonstated improvement of cardinal motor signs. Once daily DA preparations may be better tolerated by the elderly at efficacious doses, perhaps due to less peak-dose adverse effects, or other benefits of more consistent levels. The use of age as a pivotal factor in current algorithms may need reevaluation as once daily formulations become available. P2.087 The role of dopamine receptors in the induction of levodopa-induced dyskinesia in parkinsonsian rats C. Tsironis1 , D. Stamatis2 , S. Maranis1 , E. Tzika2 , A. Beris3 , S. Konitsiotis1 . 1 Department of Neurology, 2 University of Ioannina (Medical School), 3 Department of Orthopaedics, University Hospital of Ioannina, Ioannina, Greece Introduction: Treatment of Parkinson Disease (PD) with L-Dopa or Dopamine Agonists is complicated by the appearance of involuntary movements (Levodopa-Induced Dyskinesia [LID]). It is imperative to find the best starting treatment for PD in order to reduce the incidence of LID. Objective: Role of each dopamine receptor in the evolution of LID. Material and Methods: Male Wistar rats were induced parkinsonian by microinjection of 6-OHDA. After four to six weeks, animals were separated into four treatment groups. First group (n = 6): received SKF38391 (D1 dopamine agonist) for seven days and SKF38391 plus L-Dopa for at least seven more days. In the second and third group, following the same time sheet, instead of SKF, we administered Quinpirole (D2 agonist) and 7-OHDPAT (D3 agonist). The last group of animals received L-Dopa for 14 days. AIMs were quantified using the rat AIM rating scale. A dyskinesia severity index (DSI) was used to quantify the severity of AIMs in relation to the magnitude and duration of L-dopa response. Results: The mean DSI, in each group, for the first seven days was: 9.4 (SKF), 7.0 (Quinpirole), 4.4 (7-OH-DPAT), 26.0 (L-Dopa) [p = 0.000].
In addition, for days 8–14, the mean DSI was: 16.5 (SKF), 20.6 (Quinpirole), 14.4 (7-OH-DPAT), 30.0 (L-Dopa) [p = 0.000]. The statistical method that was used was one-way-ANOVA. Conclusion: The best starting treatment for PD, in order to reduce the incidence of LID, is a D3 agonist. The D1 and D2 agonists are also, better treatment choices than the worst starting treatment, in regard to LID, which is L-Dopa. Mean DSI
1–7 days 8–14 days
SKF
Quinpirole
7-OH-DPAT
L-Dopa
9.4 16.5
7.0 20.6
4.4 14.4
26.0 30.0
P2.088 Patient and carer opinions of apomorphine use in Parkinson’s disease S. O’Sullivan1 , S. Beddow2 , P. Lambert2 , G. Montgomery2 , J. Singh2 , J. Mills3 , N. Duffy2 . 1 Institute of Neurology, University College London, London, 2 Britannia Pharmaceuticals Ltd., Surrey, 3 Genus Pharmaceuticals Ltd., Newbury, UK Background: There are few data relating to patients’ and carers’ impression of apomorphine use in PD. Aims: To assess patients’ opinions of the use of apomorphine in PD, and to identify factors influencing attitudes regarding this treatment amongst patients and their carers. Methods: 1052 patients currently using apomorphine for PD were sent questionnaires by Britannia Pharmaceuticals. Results: 271 Patients returned the questionnaires. Patients had mean disease duration of 12.2±6.6 years, and were using apomorphine for 4.2±4.4 years. 43% of patients were “satisfied” and 30% described themselves as “happy” with apomorphine, and 40.3% felt their levels of independence were “about the same” or improved since starting on apomorphine. 52% of patients felt they would have benefitted from starting apomorphine treatment at an earlier stage in their disease. A positive attitude towards initiating apomorphine treatment was associated with the presence of uncontrolled and unpredictable “off” episodes (p = 0.038); symptoms upon waking, before first oral medication was effective (p = 0.008); and the initial opinion of the carer regarding apomorphine (p < 0.0005). Factors associated with a more positive current attitude amongst patients towards apomorphine include: initial attitude to apomorphine treatment (p < 0.0005); support received from doctor (p = 0.02); support received from PD nurse (p = 0.036). Discussion: Our findings suggest that severity of particular symptoms, rather than disease duration, are relevant when considering starting apomorphine. The degree of support received from their doctors, PD nurses and pharmacists was associated with a more positive current attitude amongst patients and their carers towards treatment with apomorphine. P2.089 Efficacy of pramipexole extended release (ER) and switching from pramipexole immediate release (IR) to ER in Japanese advanced PD patients Y. Mizuno1 , M. Yamamoto2 , S. Kuno3 , K. Hasegawa4 , T. Kagimura5 , N. Hattori1 , The Japanese Pramipexole-ER Study Group. 1 Juntendo University School of Medicine, Tokyo, 2 Kagawa Prefectual Central Hospital, Takamatsu, 3 National Center Hospital of Neurology and Psychiatry, Tokyo, 4 National Hospital Organization Sagamihara National Hospital, Sagamihara, 5 Nippon Boehringer Ingelheim Co., Ltd, Tokyo, Japan Objective: To investigate the efficacy and tolerability of pramipexole ER in comparison with those of pramipexole IR in Japanese patients with advanced Parkinson’s disease (PD), and to assess the effects of switching from IR to ER.
Poster presentations / Parkinsonism and Related Disorders 15S2 (2009) S29–S199
P2.086 Efficacy and tolerability of prolonged-release Ropinirole (Requip XL) in the elderly with Parkinson’s disease S. Isaacson1 , J. Isaacson2 , D. Kreitzman3 . 1 Parkinson’s C.O.R.E. Institute of Boca Raton, 2 PREF Summer Research Program, Parkinson’s C.O.R.E. Institute of Boca Raton, Boca Raton, FL, 3 Parkinson’s Disease and Movement Disorders Center of Long Island, Commack, NY, USA Objective: Retrospective review of efficacy and tolerability of the prolonged-release ropinirole (Requip XL) in the elderly with Parkinson’s disease (PD). Background: Dopamine agonists (DA) have established efficacy in PD, but guidelines utilize age to help guide therapeutic decisionmaking. Clinical trials often have limited enrollment of elderly, so treatment is often based on anecdotal experience rather than evidence-based. Ropinirole prolonged-release provides more consistent plasma levels, so it may be less likely to cause intolerable peak dopaminergic adverse effects. Methods: projectSUNSHINE, an epidemiological multi-center longitudinal PD research database initiative, 70% of patients are over the age of seventy. projectSUNSHINE tracks extensive demographic and clinical information, at each patient encounter, including rating scales, motor fluctuations, non-motor symptoms, abd concomitant medical history. Results: Using the projectSUNSHINE database, we identified over 250 consecutive patients with PD who were treated with ropinirole prolonged-release (Requip XL). The clinical course, treatment outcome, and dosing of these ropinirole treated patients were reviewed. UPDRS II and III subscores improved, often at doses 2–8 mg. Adverse effects were mild and did not limit treatment for most patients, even those intolerant of immediate-release. Conclusion: Ropinirole prolonged-release (Requip XL) was generally well tolerated in this elderly cohort, and demonstated improvement of cardinal motor signs. Once daily DA preparations may be better tolerated by the elderly at efficacious doses, perhaps due to less peak-dose adverse effects, or other benefits of more consistent levels. The use of age as a pivotal factor in current algorithms may need reevaluation as once daily formulations become available. P2.087 The role of dopamine receptors in the induction of levodopa-induced dyskinesia in parkinsonsian rats C. Tsironis1 , D. Stamatis2 , S. Maranis1 , E. Tzika2 , A. Beris3 , S. Konitsiotis1 . 1 Department of Neurology, 2 University of Ioannina (Medical School), 3 Department of Orthopaedics, University Hospital of Ioannina, Ioannina, Greece Introduction: Treatment of Parkinson Disease (PD) with L-Dopa or Dopamine Agonists is complicated by the appearance of involuntary movements (Levodopa-Induced Dyskinesia [LID]). It is imperative to find the best starting treatment for PD in order to reduce the incidence of LID. Objective: Role of each dopamine receptor in the evolution of LID. Material and Methods: Male Wistar rats were induced parkinsonian by microinjection of 6-OHDA. After four to six weeks, animals were separated into four treatment groups. First group (n = 6): received SKF38391 (D1 dopamine agonist) for seven days and SKF38391 plus L-Dopa for at least seven more days. In the second and third group, following the same time sheet, instead of SKF, we administered Quinpirole (D2 agonist) and 7-OHDPAT (D3 agonist). The last group of animals received L-Dopa for 14 days. AIMs were quantified using the rat AIM rating scale. A dyskinesia severity index (DSI) was used to quantify the severity of AIMs in relation to the magnitude and duration of L-dopa response. Results: The mean DSI, in each group, for the first seven days was: 9.4 (SKF), 7.0 (Quinpirole), 4.4 (7-OH-DPAT), 26.0 (L-Dopa) [p = 0.000].
In addition, for days 8–14, the mean DSI was: 16.5 (SKF), 20.6 (Quinpirole), 14.4 (7-OH-DPAT), 30.0 (L-Dopa) [p = 0.000]. The statistical method that was used was one-way-ANOVA. Conclusion: The best starting treatment for PD, in order to reduce the incidence of LID, is a D3 agonist. The D1 and D2 agonists are also, better treatment choices than the worst starting treatment, in regard to LID, which is L-Dopa. Mean DSI
1–7 days 8–14 days
SKF
Quinpirole
7-OH-DPAT
L-Dopa
9.4 16.5
7.0 20.6
4.4 14.4
26.0 30.0
P2.088 Patient and carer opinions of apomorphine use in Parkinson’s disease S. O’Sullivan1 , S. Beddow2 , P. Lambert2 , G. Montgomery2 , J. Singh2 , J. Mills3 , N. Duffy2 . 1 Institute of Neurology, University College London, London, 2 Britannia Pharmaceuticals Ltd., Surrey, 3 Genus Pharmaceuticals Ltd., Newbury, UK Background: There are few data relating to patients’ and carers’ impression of apomorphine use in PD. Aims: To assess patients’ opinions of the use of apomorphine in PD, and to identify factors influencing attitudes regarding this treatment amongst patients and their carers. Methods: 1052 patients currently using apomorphine for PD were sent questionnaires by Britannia Pharmaceuticals. Results: 271 Patients returned the questionnaires. Patients had mean disease duration of 12.2±6.6 years, and were using apomorphine for 4.2±4.4 years. 43% of patients were “satisfied” and 30% described themselves as “happy” with apomorphine, and 40.3% felt their levels of independence were “about the same” or improved since starting on apomorphine. 52% of patients felt they would have benefitted from starting apomorphine treatment at an earlier stage in their disease. A positive attitude towards initiating apomorphine treatment was associated with the presence of uncontrolled and unpredictable “off” episodes (p = 0.038); symptoms upon waking, before first oral medication was effective (p = 0.008); and the initial opinion of the carer regarding apomorphine (p < 0.0005). Factors associated with a more positive current attitude amongst patients towards apomorphine include: initial attitude to apomorphine treatment (p < 0.0005); support received from doctor (p = 0.02); support received from PD nurse (p = 0.036). Discussion: Our findings suggest that severity of particular symptoms, rather than disease duration, are relevant when considering starting apomorphine. The degree of support received from their doctors, PD nurses and pharmacists was associated with a more positive current attitude amongst patients and their carers towards treatment with apomorphine. P2.089 Efficacy of pramipexole extended release (ER) and switching from pramipexole immediate release (IR) to ER in Japanese advanced PD patients Y. Mizuno1 , M. Yamamoto2 , S. Kuno3 , K. Hasegawa4 , T. Kagimura5 , N. Hattori1 , The Japanese Pramipexole-ER Study Group. 1 Juntendo University School of Medicine, Tokyo, 2 Kagawa Prefectual Central Hospital, Takamatsu, 3 National Center Hospital of Neurology and Psychiatry, Tokyo, 4 National Hospital Organization Sagamihara National Hospital, Sagamihara, 5 Nippon Boehringer Ingelheim Co., Ltd, Tokyo, Japan Objective: To investigate the efficacy and tolerability of pramipexole ER in comparison with those of pramipexole IR in Japanese patients with advanced Parkinson’s disease (PD), and to assess the effects of switching from IR to ER.