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P.1.c.032 Ropinirole as a coadjuvant treatment in the management of refractory patients with fibromyalgia: a case series
S270
P.l.c Basic and clinical neuroscience - Neuropharmacology
I would like the disclosure to appear in the published paper References
[1] Jon Russell, MD, PhD. Fibromyalgia Syndrome: Approach to Management. CNS Spectr. 2008;13:3(Suppl 5):27-33. [2] Crofford LJ, Rowbotham MC, Mease PJ, et al. Pregabalin for the treatment of fibromyalgia syndrome: results of a randomized, doubleblind, placebo-controlled trial. Arth Rheum. 2005;52:1264-1273. [3] Roland Staud, MD, and Michael Spaeth, MD Psychophysical and Neurochemical Abnormalities of Pain Processing in Fibromyalgia. CNS Spectr.2008;13:3(Supp15):12-l7.
1P.1.C.0321 Ropinirole as a coadjuvant treatment in the management of refractory patients with fibromyalgia: a case series
IS. Vilchez 1 " E.P. Calandre 1 , F. Rico-Villademoros 1 , R. Molina-Barea1 , C.M. Rodriguez-Lopez 1 , I Garcia-Carrillo 1 . 1 Universidad de Granada, Instituto de Neurociencias, Granada, Spain Purpose: Dopamine agonists could be effective in the treatment of fibromyalgia; to date, pramiprexole has shown to be better than placebo at this respect [1]. The present study was done to assess the potential efficacy and tolerability of add-on treatment with ropinirole in fibromyalgia management. Methods: Open-label study conducted in patients diagnosed of fibromyalgia according to the American College of Rheumatology criteria who had not responded satisfactorily to previous fibromyalgia treatments. Ropinirole, in a starting dose of 0.25 mg at night, was added to the current patients' treatment regimen; subsequent dose adjustments were done at 2-weeks intervals according to the patients' therapeutic response. Patients were followed during 12 weeks and evaluations were done at baseline and at weeks 6 and 12. Main outcome measure was the mean change from baseline to endpoint in the Fibromyalgia Impact Questionnaire (FIQ) score. Secondary outcome measures included mean changes from baseline to endpoint in the scores of the Pittsburgh Sleep Quality Index (PSQI), the Brief Pain Inventory (BPI), the Hospital Anxiety and Depression Scale (HADS), and the SF-36 Health Survey (SF-36), which was administered at baseline and at week 12. Drug-emergent adverse reactions were recorded. Analysis of data were done on the Intention-To-Treat (ITT) sample, which included all patients who started ropinirole treatment. Results were analyzed by means of repeated measures analysis of variance. Effects sizes (ES) were also calculated. Parameter
Baseline
Week 6
Week 12
P
ES at endpoint
FIQ total PSQI total BPI severity BPI interference HADS anxiety HADS depression SF-36 Bodily Pain SF-36 Global Health SF-36 Mental Health SF-36 Vitality
77.7±14.6 l6.8±3.4 7.36±1.6 7.77±1.8 l4.6±3.4 l2.8±4.l 10.9±12.2 20.9±12.l 25.4±15.3 l1.6±10.0
68.6±17.6 l5.4±3.8 6.25±2.3 6.78±2.6 13.3±4.l 11.3±4.5
65.3±19.8 l4.9±4.2 6.l4±1.9 6.86±2.5 l2.6±4.l 11.3±5.0 19.6±15.9 26.3±13.2 35.4±18.8 20.2±16.7
0.0047 0.0074 0.0001 0.0143 0.0004 n.s. 0.0090 0.0033 0.0069 0.0087
0.85 0.56 0.76 0.51 0.59 0.37 0.71 0.45 0.66 0.86
Results: The sample included twenty-eight patients, 24 women and 4 men, aged 27-67 (49.8±9.4) years. Comorbity with other
diseases was high (2-11, 5±2). Ten patients (35.71%) withdrew from the study, six of them due to drug-related side effects. Final ropinirole daily doses ranged from 1 to 4 mg (2.5±0.8). FIQ total scores, BPI average pain severity scores, BPI global interference scores, PSQI scores, and HADS anxiety scores decreased significantly with ES moderate to large. Four of the eight scales of the SF-36 showed significant score's increases, namely Bodily Pain, Global Health, Mental Health, and Vitality. Data are shown in the table. Most frequent side effects included nausea/vomiting (28.6%), dizziness (21.4%), drowsiness (21.4%), headache (17.9%), tachycardia (10.7%), tremor (10.7%) and peripheral edema (10.7%). Conclusions: In our sample, ropinirole significantly improved fibromyalgia symptomatology and quality of life. Tolerability, however, was poor, although this finding could be related with the fact that patients were already receiving one or more drugs for fibromyalgia and for associated illnesses. Despite the limitations related with the open label design and sample size, our data suggest that ropinirole could be useful in fibromyalgia management. References
[1] Holman A.I., Myers R.R., 2005 A randomized, double-blind, placebocontrolled trial of pramipexole, a dopamine agonist, in patients with fibromyalgia receiving concomitant medications. Arthritis Rheum 52, 2495-2505.
IP.1.c.0331 Effects of carnosine on long-term plasticity of perforant pathway/dentate gyrus synapses in rats: an in vivo model
N. Dolu1 " C. Suer1 , S. Artis 1 , S. Aydogan1 . 1Erciyes University Medical Faculty, Physiology, Kayseri, Turkey Aim and Introduction: Carnosine is one of the most important antioxidants of brain extracellular matrix and the growth of the synaptic spine is controlled in part by the balance in the synapse between neurodestructive pro-oxidants and neuroprotective antioxidants. Previous studies demonstrated that soluble guanylate cyclase (sGC) inhibitors suppress LTP [1]. Carnosine is also a selective inhibitor of NO-dependent activation of guanylate cyclase [2]. Therefore, we aimed to examine the effect of carnosine on the hippocampal-dependent learning in perforant pathway/dentate gyrus synapses in vivo. Methods: Experimental procedures were approved by the Institutional Animal Care and Use Committee of Erciyes University. Rats were anesthetized with urethane and the head was fixed in a stereotaxic head holder for LTP recording. A bipolar stimulating electrode was placed to the lateral perforant path and a glass micropipette with double channel was placed in the dentate gyrus as recording electrode. Artificial cerebrospinal fluid (to control group) or carnosine (O.I!!g/!!L, 1 !!g/!!L) was infused to dentate gyrus. Firstly, the input-output (I/O) function were measured to stimulation applied to the lateral perforant path. Stimulus intensity that produced 50% of maximum response (Le. test pulse) was used. Experiment were started to apply test stimuli at every 30 sec. First 20 min of the experiment was the balance period; following 2 min of this period, aCSF or carnosine were infused. At 25th, 30th, 35th and 40th minute, the high frequency stimulation protocol (HFS, 100 Hz, 1 s) applied. Then application of test stimuli was continued up to 180th minutes at every 30 sec. The slope of fEPSP was calculated as the amplitude change at 20-80% of the voltage difference between the start of the waveform and the fEPSP amplitude at the onset of PS. The PS
P.l.c Basic and clinical neuroscience - Neuropharmacology
I would like the disclosure to appear in the published paper References
[1] Jon Russell, MD, PhD. Fibromyalgia Syndrome: Approach to Management. CNS Spectr. 2008;13:3(Suppl 5):27-33. [2] Crofford LJ, Rowbotham MC, Mease PJ, et al. Pregabalin for the treatment of fibromyalgia syndrome: results of a randomized, doubleblind, placebo-controlled trial. Arth Rheum. 2005;52:1264-1273. [3] Roland Staud, MD, and Michael Spaeth, MD Psychophysical and Neurochemical Abnormalities of Pain Processing in Fibromyalgia. CNS Spectr.2008;13:3(Supp15):12-l7.
1P.1.C.0321 Ropinirole as a coadjuvant treatment in the management of refractory patients with fibromyalgia: a case series
IS. Vilchez 1 " E.P. Calandre 1 , F. Rico-Villademoros 1 , R. Molina-Barea1 , C.M. Rodriguez-Lopez 1 , I Garcia-Carrillo 1 . 1 Universidad de Granada, Instituto de Neurociencias, Granada, Spain Purpose: Dopamine agonists could be effective in the treatment of fibromyalgia; to date, pramiprexole has shown to be better than placebo at this respect [1]. The present study was done to assess the potential efficacy and tolerability of add-on treatment with ropinirole in fibromyalgia management. Methods: Open-label study conducted in patients diagnosed of fibromyalgia according to the American College of Rheumatology criteria who had not responded satisfactorily to previous fibromyalgia treatments. Ropinirole, in a starting dose of 0.25 mg at night, was added to the current patients' treatment regimen; subsequent dose adjustments were done at 2-weeks intervals according to the patients' therapeutic response. Patients were followed during 12 weeks and evaluations were done at baseline and at weeks 6 and 12. Main outcome measure was the mean change from baseline to endpoint in the Fibromyalgia Impact Questionnaire (FIQ) score. Secondary outcome measures included mean changes from baseline to endpoint in the scores of the Pittsburgh Sleep Quality Index (PSQI), the Brief Pain Inventory (BPI), the Hospital Anxiety and Depression Scale (HADS), and the SF-36 Health Survey (SF-36), which was administered at baseline and at week 12. Drug-emergent adverse reactions were recorded. Analysis of data were done on the Intention-To-Treat (ITT) sample, which included all patients who started ropinirole treatment. Results were analyzed by means of repeated measures analysis of variance. Effects sizes (ES) were also calculated. Parameter
Baseline
Week 6
Week 12
P
ES at endpoint
FIQ total PSQI total BPI severity BPI interference HADS anxiety HADS depression SF-36 Bodily Pain SF-36 Global Health SF-36 Mental Health SF-36 Vitality
77.7±14.6 l6.8±3.4 7.36±1.6 7.77±1.8 l4.6±3.4 l2.8±4.l 10.9±12.2 20.9±12.l 25.4±15.3 l1.6±10.0
68.6±17.6 l5.4±3.8 6.25±2.3 6.78±2.6 13.3±4.l 11.3±4.5
65.3±19.8 l4.9±4.2 6.l4±1.9 6.86±2.5 l2.6±4.l 11.3±5.0 19.6±15.9 26.3±13.2 35.4±18.8 20.2±16.7
0.0047 0.0074 0.0001 0.0143 0.0004 n.s. 0.0090 0.0033 0.0069 0.0087
0.85 0.56 0.76 0.51 0.59 0.37 0.71 0.45 0.66 0.86
Results: The sample included twenty-eight patients, 24 women and 4 men, aged 27-67 (49.8±9.4) years. Comorbity with other
diseases was high (2-11, 5±2). Ten patients (35.71%) withdrew from the study, six of them due to drug-related side effects. Final ropinirole daily doses ranged from 1 to 4 mg (2.5±0.8). FIQ total scores, BPI average pain severity scores, BPI global interference scores, PSQI scores, and HADS anxiety scores decreased significantly with ES moderate to large. Four of the eight scales of the SF-36 showed significant score's increases, namely Bodily Pain, Global Health, Mental Health, and Vitality. Data are shown in the table. Most frequent side effects included nausea/vomiting (28.6%), dizziness (21.4%), drowsiness (21.4%), headache (17.9%), tachycardia (10.7%), tremor (10.7%) and peripheral edema (10.7%). Conclusions: In our sample, ropinirole significantly improved fibromyalgia symptomatology and quality of life. Tolerability, however, was poor, although this finding could be related with the fact that patients were already receiving one or more drugs for fibromyalgia and for associated illnesses. Despite the limitations related with the open label design and sample size, our data suggest that ropinirole could be useful in fibromyalgia management. References
[1] Holman A.I., Myers R.R., 2005 A randomized, double-blind, placebocontrolled trial of pramipexole, a dopamine agonist, in patients with fibromyalgia receiving concomitant medications. Arthritis Rheum 52, 2495-2505.
IP.1.c.0331 Effects of carnosine on long-term plasticity of perforant pathway/dentate gyrus synapses in rats: an in vivo model
N. Dolu1 " C. Suer1 , S. Artis 1 , S. Aydogan1 . 1Erciyes University Medical Faculty, Physiology, Kayseri, Turkey Aim and Introduction: Carnosine is one of the most important antioxidants of brain extracellular matrix and the growth of the synaptic spine is controlled in part by the balance in the synapse between neurodestructive pro-oxidants and neuroprotective antioxidants. Previous studies demonstrated that soluble guanylate cyclase (sGC) inhibitors suppress LTP [1]. Carnosine is also a selective inhibitor of NO-dependent activation of guanylate cyclase [2]. Therefore, we aimed to examine the effect of carnosine on the hippocampal-dependent learning in perforant pathway/dentate gyrus synapses in vivo. Methods: Experimental procedures were approved by the Institutional Animal Care and Use Committee of Erciyes University. Rats were anesthetized with urethane and the head was fixed in a stereotaxic head holder for LTP recording. A bipolar stimulating electrode was placed to the lateral perforant path and a glass micropipette with double channel was placed in the dentate gyrus as recording electrode. Artificial cerebrospinal fluid (to control group) or carnosine (O.I!!g/!!L, 1 !!g/!!L) was infused to dentate gyrus. Firstly, the input-output (I/O) function were measured to stimulation applied to the lateral perforant path. Stimulus intensity that produced 50% of maximum response (Le. test pulse) was used. Experiment were started to apply test stimuli at every 30 sec. First 20 min of the experiment was the balance period; following 2 min of this period, aCSF or carnosine were infused. At 25th, 30th, 35th and 40th minute, the high frequency stimulation protocol (HFS, 100 Hz, 1 s) applied. Then application of test stimuli was continued up to 180th minutes at every 30 sec. The slope of fEPSP was calculated as the amplitude change at 20-80% of the voltage difference between the start of the waveform and the fEPSP amplitude at the onset of PS. The PS