The tolerability and efficacy of entacapone over 3 years in patients with Parkinson's disease.

The long-term safety and efficacy of the catechol-O-methyltransferase (COMT) inhibitor entacapone was investigated in a 3-year open-label extension of the 6-month double-blind placebo-controlled Nordic (NOMECOMT) study. After a wash-out following this study, 132 patients with Parkinson's disease (PD) experiencing motor fluctuations treated with levodopa/dopa decarboxylase (DDC) inhibitor received additional therapy with entacapone 200 mg, administered with each dose of levodopa. The most common adverse events (AEs) were insomnia (30%), dizziness (20%), nausea (20%), aggravated parkinsonism (17%) and hallucinations (14%). Only 19 (14%) patients discontinued because of AEs. Most dopaminergic AEs occurred shortly after initiation of entacapone, and these could be managed by levodopa down-adjustment. The mean duration of benefit of a single dose of levodopa increased significantly from 2.1 to 2.8 h (P < 0.01) at 3 months and remained prolonged for the whole study. At the end of the study, the mean daily dose of levodopa was significantly decreased from baseline (from 737 to 696 mg; P < 0.05). The patients' global assessment indicated that 69% of patients improved when given entacapone and this proportion was maintained until the end of the study (64%). There was a significant worsening of disability upon withdrawal of entacapone. In conclusion, entacapone given in combination with levodopa, has a good long-term safety profile and a sustained beneficial effect in patients with PD with motor fluctuations.

Entacapone enhances the response to levodopa in parkinsonian patients with motor fluctuations. Nomecomt Study Group.

OBJECTIVE: To study the effect and safety of entacapone as an adjunct to levodopa treatment in patients with PD with wearing-off motor fluctuations. BACKGROUND: Entacapone is a catechol-O-methyltransferase (COMT) inhibitor that has been shown to increase the area under the concentration-time curve of plasma levodopa by decreasing its systemic elimination, thereby promoting and improving therapeutic response to it. METHODS: A total of 171 parkinsonian patients with wearing-off-type motor fluctuations participated in a 6-month randomized, placebo-controlled, double-blind, parallel-group study. The extent of therapeutic response was elicited in the first hand with home diary recordings of "on" and "off" times by the patient and with Unified Parkinson's Disease Rating Scale scoring by the examiner. The patients took either 200 mg entacapone or identical placebos concomitantly with each daily levodopa dose (four to 10 times a day). RESULTS: Patients' home diaries indicated that entacapone increased the mean (+/- SD) "on" time significantly (9.3 +/- 2.2 to 10.7 +/- 2.2 hours; p < 0.01) and correspondingly decreased the "off" time significantly (5.3 +/- 2.2 to 4.2 +/- 2.2 hours; p < 0.001). The average benefit derived from a daily levodopa dose as related by the patients was increased significantly (p < 0.01). The daily levodopa dose was reduced significantly in the entacapone group, the difference between the groups being 102 mg (p < 0.01). The entacapone-derived increase in the benefit from levodopa was lost almost completely following its withdrawal. Entacapone was well tolerated. Dopaminergic adverse events, which increased, were ameliorated by reducing the levodopa dose. Diarrhea was the most common nondopaminergic adverse event. CONCLUSIONS: Long-term entacapone treatment effectively prolonged the beneficial response to levodopa in parkinsonian patients with the wearing-off phenomenon. The improvement occurred irrespective of the reduction of the levodopa dose.

Sustained-release Madopar HBS compared with standard Madopar in the long-term treatment of de novo parkinsonian patients.

In this Danish-Norwegian randomized double-blind parallel-group multicentre study, we compared the therapeutic response of slow-release Madopar HBS to standard Madopar in 134 de novo patients with idiopathic Parkinson's disease during a 5-year period. The drugs were dosed according to the individual need of the patients. The Webster, NUDS, UPDRS and Hoehn & Yahr scales were used for evaluation of symptoms. Addition of a morning dose of standard Madopar 62.5 mg was allowed after 6 months. Bromocriptine could be administered but not Selegiline. Sixty-five patients got Madopar HBS and 69 standard Madopar. Surprisingly, no differences were found as to the mean daily levodopa dose, the mean number of daily doses or the use of the doses of bromocriptine. Unexpectedly, we found a trend towards a more frequent use of a morning dose of standard Madopar in the group treated with the standard formulation. No differences were observed in the occurrence of motor fluctuations or dyskinesia, the incidence of which was relatively low. Sustained-release Madopar (HBS) thus proved to be as effective as standard Madopar in the long-term treatment of de novo parkinsonian patients, but the drug showed no advantage in postponing or reducing the long-term levodopa treatment problems.

Therapeutic experiences with 947 epileptic out-patients in oxcarbazepine treatment.

Efficacy and tolerability of the new antiepileptic drug oxcarbazepine, was evaluated in a retrospective multicentre study. The records of all 947 epilepsy patients treated with oxcarbazepine in the eight participating centres from 1981 through 1990 were examined. The median daily dose of oxcarbazepine was 30 mg/kg in children, 18 mg/kg in adults, and 15 mg/kg in elderly patients, given b.i.d. or t.i.d. The mean plasma levels of the main active metabolite of oxcarbazepine was 88, 79, and 68 mumol/l in children, adults, and elderly, respectively. In patients shifted to oxcarbazepine treatment, seizure frequency was unchanged in 51-66%, 32-48% had a decrease, and 1-10% an increase in seizure frequency, considering the individual seizure types separately. Adverse events were reported in one third of patients, most frequently affecting the CNS (dizziness: 6%; sedation: 6%; fatigue: 6%). Rash was reported in 6% of patients, half of these patients had previously had an allergic reaction to carbamazepine. Hyponatremia was found in about a quarter of the patients from whom data were available. No congenital malformations were seen in nine live-born, first trimester oxcarbazepine-exposed children.

Bladder function in healthy elderly males.

Bladder function was studied in 20 healthy elderly male volunteers using cystometry, uroflowmetry and voiding cystourethrography. Two persons were excluded from the study as neurological examination had shown evidence of organic neurological disease, and one person did not complete the study. 53% of the remaining 17 persons had detrusor hyperreflexia. Urinary flow rates were reduced and maximal intravesical pressures elevated in the persons studied, although they claimed to have a normal voiding pattern. No correlation was found between the reduction of urinary flow rate respectively increase in maximal intravesical pressure and the presence of detrusor hyperreflexia. The high incidence of detrusor reflex disturbances thus suggests that incipient infravesical obstruction in old age and possible subclinical impairment of the central nervous control of the micturition reflex are major etiological factors in detrusor hyperreflexia.

Disturbances of micturition in Parkinson's disease.

During the years 1970-1974, a total of 44 patients referred by neurologists to the Urological Laboratory were classified in the following groups: paralysis agitans (27), postencephalitic parkinsonism (5), cerebral arteriosclerosis and parkinsonism (7) and cerebral arteriosclerosis and parkinsonism, suspected (5). Bladder function was assessed on the basis of cystometry and urodynamic investigation. A high frequency of supranuclear bladder paresis (SNP) was found, although unequally distributed in the different diagnostic groups. Stereotactic operations on the thalamic nuclei seemed to be correlated with SNP. The question was raised whether SNP was part of the parkinsonian syndrome or merely signs and symptoms related to ageing.