[Direct switch from conventional levodopa to stalevo (levodopa/carbidopa/entacapone) improves quality of life in Parkinson's disease: results of an open-label clinical study].

UNLABELLED: The most effective symptomatic treatment for Parkinson's disease (PD) is levodopa/dopa decarboxylase (DDC)-inhibitor or conventional levodopa. However, after a few years of treatment, motor complications may develop, such as <> and dyskinesias. Symptoms of <> can be both motor symptoms, e.g. tremor and bradykinesia, as well as non-motor symptoms (pain, mood changes and anxiety). The development of these complications may affect the patients quality of life (QOL). To investigate the efficacy and safety direct switch from conventional levodopa to stalevo(levodopa/carbidopa/entacapone) in PD patients with fluctuations and dyskinesias. METHODS/PATIENTS: Thirty four patients with PD were recruited in the study. The mean age (+/-SD) of the patients was 64,5+/-8,3 years, the mean duration of PD (+/-SD) was 5,9+/-3,1 years, the mean H&Y was 2,5+/-0,5. All patients experienced fluctuations and six had dyskinesias (one patient had biphasic dyskinesias with painful dystonia). The mean baseline levodopa dose was 785,8+/-150,2 mg per day taking in three to six doses. Assessments were performed before, end of 1, 4 and 12 weeks of treatment period and consisted of Hoen/Yahr stages (H&Y), II and III parts of the Unified Parkinson's Disease Rating Scale (UPDRS), patients diaries with registration <> periods, scale EQ-5D, WOQ-9. While switching from conventional levodopa to stalevo taking single levodopa doses were equivalent or less. Maximum allowed doses of stalevo were four times per day. RESULTS: Direct switch to stalevo results in improvement of motor and non-motor symptoms (pain and anxiety) in fluctuating patients and significant prolongation of <> periods (p<0.01). We observed dramatic improvement biphasic dyskinesias with painful dystonia and reducing severity of dyskinesias in others patients. Improvement was seen in QOL by scale EQ-5D from 10,7+/-1,9 to 8,6+/-2,1 points (p<0,05). Conclusions. Switching from conventional levodopa to stalevo is efficacy and safety and can significantly improve QOL PD patients with fluctuations and dyskinesias.

[Pain and depression in Parkinson's disease: new therapeutic possibilities of pramipexole].

An aim of a study was to establish the relationship between pain, motor complications and depression in Parkinson's disease and evaluate an effect of the 3 months therapy with the dopamine receptor agonist pramipexole (mirapex). Seventy-eight patients with idiopathic parkinsonism, aged 56-73 years, including 18 patients in stage 1-1,5 of the disease; 31 patients - in stage 2; 20 patients - in stage 3 and 9 patients - in stage 4, were studied. A stable response to the therapy was observed in 28 patients, motor complications in 50. A patient's state was assessed with widely-used scales. Thirty patients were assigned to pramipexole as an add-on therapy to L-DOPA and amantadin. Patients with dementia did not receive pramipexole. Thirty-five patients (44,8%) had pain complaints. This percentage was significantly higher (62%) in patients with motor complications. Multiple regression analysis revealed that pain scores were significantly correlated with motor complication and motor fluctuation scores. Back pain scores were correlated with an extent of posture disturbances. Mild depression and depressed mood were found in 37 patients (47,4%). VAS scores in these patients were significantly higher compared to patients without mood disturbances. The intensity of pain was correlated with depression severity. Patients treated with mirapex reported the reduction of pain by 48,2% (p<0,0001) during the "on-period". During the "off-period", the reduction of pain intensity was less (23,7%) but still significant. Depression scores were decreased to the end of the 12th week of treatment from 15,2+/-2,3 to 10,4+/-3,5 (p<0,0001).

[Memantine (akatinol) therapy of cognitive impairment in Parkinson's disease complicated by dementia].

The study has investigated the effect of NMDA-glutamate receptor antagonist memantine in the 52-weeks therapy of 32 PD patients with dementia (PDD) compared with the control group (30 cases). Patients of the active group received memantine (20 mg per day) additionally to dopaminergic therapy. Patients from the control group continued the treatment with antiparkinsonian drugs. Cognitive, psychiatric and motor symptoms have been assessed before and after 12, 24 and 52 weeks of the study using clinical assessment as well as rating scales including the Unified Parkinson's Disease Rating Scale (UPDRS), the Mini-Mental State Examination (MMSE), ADAS-cog, clock drawing test, D-KEFS Verbal Fluency test, the Frontal Assessment Battery (FAB), the Neuropsychiatric Inventory (NPI-12) and the Disability Assessment for Dementia Scale (DAD). The plasma total Hcy level was determined by high-performance liquid chromatography. Patients treated with memantine had better MMSE (p<0,05), ADAS-cog (p<0,05), clock drawing test (p<0,05) and FAB (p<0,01) scores compared to patients in the control group at week 24. Patients with elevated Hcy demonstrated a significantly better response to memantine therapy versus the controls with elevated Hcy at week 24, 52 with respect to all efficacy measures (UPDRS, MMSE, ADAS-cog, D-KEFS, Verbal Fluency test, FAB, NPI, DAD, p<0,05). The NPI individual item scores changes from baseline to week 52 have shown benefits to memantine treatment compared with the controls with significant treatment differences for disinhibition (p<0,006), irritability (p<0,04), anxiety (p<0,04) and hallucinations (p<0,048). Hyperhomocysteinemia may indicate the more rapid cognitive and motor decline in PD. The prolonged therapy with memantine in PDD led to improvements in cognitive functions and preservation of motor functional abilities as well as the amelioration of neuropsychiatric symptoms, especially in patients with hyperhomocysteinemia.

[Efficacy and safety of galantamine (reminyl) in the treatment of dementia in patients with Parkinson's disease (open-label controlled trial)].

Forty-one Parkinson's disease patients with dementia (21 galantamine group, 20--control group) with onset of dementia at least two years after the manifestation of parkinsonian symptoms participated in this open-label controlled trial of galantamine in maximum dose 16 mg/day. Cognitive, psychiatric and motor symptoms were assessed before and after 4, 12 and 24 weeks of treatment using clinical assessment as well as rating scales, including the Mini-Mental State Examination (MMSE), ADAS-cog, clock drawing test, Frontal Assessment Battery (FAB), and the Neuropsychiatric Inventory (NPI-12) with assessment of caregiver distress. Patients treated with galantamine had better scores on MMSE (p<0,05), ADAS-cog (p<0,05), clock drawing test (p<0,05) and FAB (p<0,01) to the end of the trial comparing to the control group. NPI scores on individual items changed from baseline at week 12 and 24, showing benefits of galantamine treatment as compared to the controls, with significant difference for hallucinations (p=0,0002), anxiety (p=0,04), sleep disorders (p=0,04) and apathy (p=0,006). Galantamine therapy was associated with a significant reduction in caregiver distress (p=0,007), improvement of daily life activity (p=0,003). Gait, freezing and falls were improved in the galantamine group but a mild worsening of tremor was noted in two patients. Adverse events (drooling, postural hypotension, nausea, dysuria) were observed in 7 (30%) of galantamine treated patients.