Combining entacapone with levodopa/DDCI improves clinical status and quality of life in Parkinson's Disease (PD) patients experiencing wearing-off, regardless of the dosing frequency: results of a large multicentre open-label study.

The efficacy of entacapone and its impact on patient quality of life (QOL) was investigated in an open-label study of 899 patients with idiopathic Parkinson's Disease (PD) experiencing wearing-off fluctuations. Patients were divided into 3 groups (3, 4 or 5 doses daily) based on their current levodopa dosage frequency. Patients received 200 mg entacapone with each levodopa/dopa-decarboxylase inhibitor (DDCI) dose, while continuing their same levodopa/DDCI dosage regimen for 4 weeks. Primary efficacy measure was the Investigators' Clinical Global Impression of Change (CGIC). Patient QoL was assessed using the validated 8-item Parkinson's Disease Questionnaire (PDQ-8). Investigators' CGIC revealed that 76.5% of entacapone treated patients experienced an improvement in global status after 4 weeks. Treatment with entacapone was also associated with improvement in patient QoL, with a mean reduction (improvement) in PDQ-8 score of 1.8 from baseline. This study confirms and extends the results of earlier studies demonstrating that, independent of dosing frequency, completing levodopa/DDCI therapy with entacapone provides clinically relevant improvements in global status and QoL in PD patients experiencing wearing-off on their current levodopa dosing frequency.

Selfotel in acute ischemic stroke : possible neurotoxic effects of an NMDA antagonist.

BACKGROUND AND PURPOSE: Based on neuroprotective efficacy in animal models, we evaluated the N-methyl D-aspartate antagonist Selfotel in patients with ischemic stroke, after doses up to 1.5 mg/kg were shown to be safe in phase 1 and phase 2a studies. METHODS: Two pivotal phase 3 ischemic stroke trials tested the hypothesis, by double-blind, randomized, placebo-controlled parallel design, that a single intravenous 1.5 mg/kg dose of Selfotel, administered within 6 hours of stroke onset, would improve functional outcome at 90 days, defined as the proportion of patients achieving a Barthel Index score of >/=60. The trials were performed in patients aged 40 to 85 years with acute ischemic hemispheric stroke and a motor deficit. RESULTS: The 2 trials were suspended on advice of the independent Data Safety Monitoring Board because of an imbalance in mortality after a total enrollment of 567 patients. The groups were well matched for initial stroke severity and time from stroke onset to therapy. There was no difference in the 90-day mortality rate, with 62 deaths (22%) in the Selfotel group and 49 (17%) in the placebo-treated group (RR=1.3; 95% CI 0.92 to 1.83; P=0.15). However, early mortality was higher in the Selfotel-treated patients (day 30: 54 of 280 versus 37 of 286; P=0.05). In patients with severe stroke, mortality imbalance was significant throughout the trial (P=0.05). CONCLUSIONS: Selfotel was not an effective treatment for acute ischemic stroke. Furthermore, a trend toward increased mortality, particularly within the first 30 days and in patients with severe stroke, suggests that the drug might have a neurotoxic effect in brain ischemia.

Carbamazepine in agitation and aggressive behaviour following severe closed-head injury: results of an open trial.

Ten patients presenting agitation and anger outbursts at various stages following a severe closed head injury, were treated in a prospective open trial with carbamazepine, with doses ranging from 400 to 800 mg per day, during 8 weeks. Group analysis demonstrated a statistically significant improvement of a score made up from six target items from the neurobehavioural rating scale. Improvement mainly concerned irritability and disinhibition. A statistically significant improvement was also found with the Agitated Behaviour Scale. Social functioning, as assessed by family or staff ratings of the Katz Adjustment Scale, also significantly improved. No modification of global cognitive functioning was found with the Mini Mental Status Examination. Individual analysis demonstrated that the beneficial effect was important in five cases, moderate in three patients and negligible in two cases. It is concluded that carbamazepine might help to reduce agitated behaviour in brain-injured patients. However, response to treatment demonstrated an important inter-individual variability.

Comparative effects of low and high doses of clomipramine and placebo in panic disorder: a double-blind controlled study. French University Antidepressant Group.

This study was designed to explore the dose-response relationship for clomipramine in patients with panic disorder, with or without agoraphobia. After 1 week of single-blind placebo pretreatment, 180 such patients were assigned to a multicentre placebo-controlled comparison of the effects of high and low doses of clomipramine, and were followed up for 8 weeks. In alleviating anxiety and panic disorder, both clomipramine doses were more efficacious than placebo for panic disorder and, to a lesser degree, for phobia. The lower dose was better tolerated and at least as effective as the higher dose, sometimes more so. These results indicate the clinically important possibility that low-dose clomipramine is effective and well tolerated.

[Controlled study of treatment of residual depression by clomipramine versus placebo]. / Etude contrôlée du traitement des dépressions résiduelles par la clomipramine versus placebo.

The choice of a new treatment strategy for a patient suffering from residual depression in sometimes difficult; in reality, any change in the prescription involves a risk of losing any benefit, even partial, that has recently been obtained; consequently, can one be sure that a new antidepressant treatment will be beneficial? To attempt to find the answer to this question, the Laboratories Ciba-Geigy have conducted a controlled study versus placebo to evaluate the efficacy of clomipramine in residual depression which has been progressing for more than a year. 207 patients were pre-included in the 7-day wash-out phase and treated with placebo. During this period, a clinical examination and laboratory work-up made it possible to exclude patients with a curable cause of partial resistance to antidepressants (e.g., hypothyroidism) or who were "placebo-responders". After this run-in, 181 patients were included if they complied with the criteria characterizing a major depressive episode in partial remission (according to the DSM III-R), present for at least one year and treated throughout this period with at least two antidepressants at effective dosages. In addition, these patients had to have a score between 15 and 25 on the Montgomery and Asberg Depression Rating Scale (MADRS). The patients included were randomized into two groups, receiving either an clomipramine 75 tablet or a placebo tablet for two weeks; the dosage could be increased to two tablets as at D14 if necessary and maintained for the next six weeks. The only authorized concomitant treatments were tranquillizers (lorazepam or bromazepam) and/or non-barbiturate hypnotics (zopiclone or flunitrazepam).(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of vigilance states on paroxysmal EEG activities and clinical seizures in children.

We studied the relationships between clinical variables and those related to the states of vigilance in 18 cases of benign partial epilepsy with centro-temporal spike-waves, 22 cases of definite symptomatic partial epilepsy, and 16 cases of undetermined partial epilepsy. The time of day during which the seizures appeared and the paroxysmal activity densities during non-REM and REM sleep are not distributed differently among the 3 electro-clinical types. However, the benign epilepsy with centro-temporal spikes group had more patients with sleep-sensitive paroxysmal activities. Patients who mainly had nocturnal seizures were found to have more frequent generalized seizures and a greater sleep-sensitive paroxysmal activity. Three cases demonstrated continuous spike-waves during sleep. The patients who had little or no paroxysmal activity during sleep were the youngest. This study illustrates that sleep-sensitive seizures and paroxysmal activities are not specific to benign childhood epilepsy with centro-temporal spikes, and that seizures and paroxysmal activities are two manifestations associated with epilepsy, affected in different ways by states of vigilance.

Influence of lateralized sensorimotor and neuropsychological activities on electroencephalographic spectral power.

In order to test the effect of 'lateralized' sensorimotor and neuropsychological activities on EEG spectral power (P), we recorded EEGs over the right and left central regions with 3 different derivations C5P3/C6P4, C5Cz/C6Cz, and C5 ears-linked (EL)/C6EL in 14 young, right-handed men who underwent ten 2 min sequences including 4 during rest (3 with eyes closed (EC), 1 with eyes open (EO], and 6 during tasks reputed to involve preferentially the left (Le) or the right (Ri) hemisphere, i.e., pure left and pure right motor activity of the hand (EC), pure neuropsychological tasks consisting in lexical followed by spatial form analysis and finally mixed (neuropsychological and motor) EC tasks consisting in writing followed by left hand object recognition. Three spectral parameters P, log P and asymmetry index AI = (P Ri-P Le)/(P Ri + P Le) were calculated in 5 frequency bands theta, alpha 1, alpha 2, alpha 3 and beta 1. We observed a relationship between task complexity and P reduction on both hemispheres which was greater during rest, less during motor activity and least during mixed motor and neuropsychological activities; during EC activities more specifically involving the left hemisphere, only the comparison between rest and mixed sequences was significant. During EC activities involving the right hemisphere, both motor and mixed sequences were significantly different from rest sequences. In addition, during the EO sequences, P was usually greater than during rest. As compared to rest conditions, the AI increased during sequences preferentially involving the left hemisphere and decreased during preferentially right hemisphere activities.(ABSTRACT TRUNCATED AT 250 WORDS)