A 2-year multifactor approach of weight loss maintenance.

The overarching problem in the treatment of obesity is the consistency with which weight in treatment is regained. The aim of this study is to follow-up the patient using a multifactor approach (cognitive-behavioral therapies, diet and physical activity counselling, an "on-off" prescription of orlistat) during 4 years in order to assess the efficacy of this specific long-term weight loss maintenance programme. Weight maintenance is defined as a weight change of <2.5% of the study entry body weight. Fifty obese patients having previously lost at least 10% of their weight by any weight loss programme before entering the maintenance multifactor approach were enrolled. Ninety percent of the patients maintained more than 10% weight loss after 2 years. All the physical characteristics remained similar between study entry and 2 years after the weight loss maintenance programme. Waist and hip as well as fat mass did not show any significant differences and the mean fat mass remained stable 2 years later. In addition, all the psychological parameters analysed remained stable and in a normal range. In conclusion, this multifactor approach shows promising interim results at year-2. The multifactor approach with an "on-off" prescription of orlistat seems to be appropriate for the long term weight loss maintenance. But considering the clinical and psychological diversity of the patients, this approach has to be individually adapted for patients presenting eating behavior disorders which need a particular follow-up.

Clinical efficacy and tolerability of a new levodopa/benserazide dual-release formulation in parkinsonian patients. L-Dopa Dual-Release Study Group.

To improve the response of parkinsonian patients to L-Dopa treatment, a new preparation of L-Dopa/benserazide with dual-release properties was developed. The breakable three-layer tablets with biphasic dissolution kinetics combine the advantages of the standard and sustained-release formulations. The clinical efficacy of this new formulation was assessed in an open-label, pilot study for 14 weeks conducted by Swiss neurologists. Sixty-one parkinsonian patients were included: 5 (8%) patients were de novo, 39 (64%) had fluctuations, and 17 (28%) without fluctuations. The mean Hoehn and Yahr stage was 2.6 and the mean duration of disease was 7.4 years. The best prestudy treatment was kept stable for 2 weeks before entering the first 8-week period in which standard and/or sustained L-Dopa treatment could be either entirely or partially substituted by the dual-release formulation, which was as far as possible kept unchanged during the second 6-week period. During the substitution period, the overall dose of L-Dopa was significantly increased by 11.5%, probably reflecting some differences in the bioavailability of the various galenical formulations, and the mean daily drug intakes were reduced from 5.4 at baseline to 4.1 at week 8 (a 24% reduction, p < 0.001). Sixteen percent of the patients dropped out of the study because of unsatisfactory results, but none left for safety reasons. At the end of the study, complete substitution was attained in 71% of the patients. The remaining 27% combined the dual-release formulation with standard and/or sustained-release L-Dopa. The efficacy of treatment was assessed with the Webster Score and qualified with a mean decrease of 27% (p < 0.001) between baseline and week 14. A significant decrease of the reported adverse events such as dyskinesias and end-of-dose or wearing-off akinesias was also observed before (27 patients, 44%) and after (9 patients, 17%) the substitution (p < 0.02). These results infer that the dual-release formulation is as good as or superior to any other galenic form of L-Dopa. In conclusion, the dual-release formulation of L-Dopa either introduced or substituted for the best treatment available showed good clinical efficacy and tolerability in all stages of the evolution of idiopathic Parkinson's disease treatment in this 14-week open-label study.

Overnight sedation with midazolam or propofol in the ICU: effects on sleep quality, anxiety and depression.

OBJECTIVE: To assess and compare the impact of overnight sedation with midazolam or propofol on anxiety and depression levels, as well as sleep quality, in non-intubated patients in intensive care. DESIGN: Open, comparative prospective, randomised study. SETTING: Surgical intensive care unit (ICU) in a university hospital. PATIENTS: 40 conscious patients expected to stay in the ICU for at least 5 days who were admitted following trauma or elective orthopaedic, thoracic or abdominal surgery. MEASUREMENTS AND RESULTS: Evaluation of a self-assessment scale (Hospital Anxiety and Depression Scale, HAD) on the day following the 1st, 3rd and 5th night of sedation with either midazolam or propofol. Heart rate, pulse oximetry and blood gases were monitored. Eight patients were excluded from the analysis. The level of anxiety was severe (HAD > 10) in 31% of the patients receiving midazolam and in 26% (p = 0.1) receiving propofol after the first night of sedation with no significant improvement over the next few days. The levels of depression remained high (> 10) in 54% of patients receiving midazolam, and in 16% of the patients receiving propofol (p = 0.15). Sleep quality tended to improve during the study in the two groups. CONCLUSIONS: These data show that half of the patients in the ICU experienced high levels of anxiety and depression during the first 5 post-operative or post-trauma days in the ICU. The beneficial effects of sedation on sleep quality were comparable for midazolam and propofol, regardless of a lack of improvement in anxiety and depression. However, an improved quality of sleep could help to re-establish a physiological night and day rhythm.

[Benefits of a new galenic form of levodopa and benserazide in the treatment of patients with Parkinson disease]. / Nutzen einer neuen galenischen Form von Levodopa und Benserazid für die Behandlung von Parkinson-Patienten.

We describe a new, water-soluble formulation of levodopa plus benserazide (Madopar LIQ) for the treatment of Parkinson's disease. Two dosage strengths are available: 100 mg levodopa plus 25 mg benserazide and 50 mg levodopa plus 12.5 mg benserazide. Pharmacokinetic data show that levodopa absorption is more rapid than with standard Madopar, resulting in a shorter time to peak plasma concentration. Other pharmacokinetic values are comparable to those obtained with the standard formulation. We discuss the clinical advantages of this new water-soluble formulation, particularly when the patient requires rapid onset of action for morning or circadian akinesia. The indications of this formulation in patients with dysphagia and in other clinical situations, e.g. during the postoperative period and for levodopa dosage adjustment in ambulatory care, are discussed.

Comparison of the efficacy and tolerability of moclobemide and maprotiline in depressed patients treated by general practitioners.

We report the results of a multicenter, double-blind study conducted in a general practice setting, in which the efficacy and tolerability of moclobemide, a new antidepressant drug of the reversible inhibitor of monoamine oxidase type A class, were compared with those of maprotiline, a noradrenaline reuptake inhibitor often prescribed in the general practice setting. Participating general practitioners were required to make differential diagnoses of depressive disorders according to DSM-III criteria and then quantitatively assess the efficacy of treatment using the Hamilton Depression Rating Scale (HDRS) and the Zung self-rating depression scale (Zung SDS). One hundred thirty outpatients (mean age 48 years) with major depression according to DSM-III were randomized to receive either moclobemide 300 mg or maprotiline 75 mg daily for 4 weeks. From day 8, dosages were increased if necessary up to a maximum of 400 mg of moclobemide or 100 mg of maprotiline. The results showed that moclobemide was as effective as maprotiline (HDRS, Zung SDS); moclobemide appeared to have the same antidepressant and anxiolytic activity, but a stronger drive-enhancing effect. Moclobemide was the better-tolerated drug, producing fewer side effects than maprotiline did: in particular, fewer instances of somnolence and dry mouth. The good tolerability of the compound was confirmed by the qualitative assessments of the study physicians.

Efficacy and tolerability of moclobemide compared with fluvoxamine in depressive disorder (DSM III). A French/Swiss double-blind trial.

The efficacy and tolerability of moclobemide and fluvoxamine, two new types of antidepressant agents, were compared in a multicentre, double-blind prospective study of patients with a diagnosis of major depressive episode (DSM III). Patients were randomized to receive either moclobemide (150 mg) or fluvoxamine (50 mg) twice daily for 7 days, immediately following a washout period of at least 1 week. Dosages were increased where necessary on day 8, to a maximum of moclobemide 450 mg or fluvoxamine 200 mg and in most cases were maintained at these levels for the remainder of the study period (4-6 weeks). Both treatment groups showed a marked antidepressant effect. While both treatments were well tolerated, moclobemide showed a more favourable side-effect profile than fluvoxamine. Of the 126 patients eligible for evaluation, 34 withdrew from therapy, 22% in the moclobemide group and 30% in the fluvoxamine group. Adverse events were reported in 41.8% of patients treated with moclobemide compared to 60.3% of patients in the fluvoxamine group. Reports of dry mouth and other anticholinergic effects were more frequent among those treated with fluvoxamine. A greater number of gastrointestinal complaints, especially nausea, also occurred in the fluvoxamine-treated patients.

Theoretical considerations and perspectives on the onset of action of moclobemide.

The aim of this paper is to focus on methodological problems related to clinical studies on the onset of action of antidepressants, especially moclobemide. The methodological discussion proposed focuses on: --global efficacy as a function of time; --proposals for a specific approach to the study of the onset of action; --quality of the response and onset of action; --the dimensional level and the onset of action.

[Multicenter study comparing efficacy and tolerance of moclobemide and fluvoxamine in hospitalized and ambulatory patients with severe depressive episodes]. / Etude multicentrique comparant l'efficacité et la tolérance du moclobémide et de la fluvoxamine chez des patients hospitalisés et ambulatoires présentant un épisode dépressif majeur.

In a double blind study performed in psychiatric clinics the efficacy and tolerability of the new antidepressant Moclobemide was compared. Moclobemide belongs to a new class of substances called RIMA (Reversible Inhibitor of the monoamine oxidase type A). 61 patients with major depression (according to DSM-III) were either treated with Moclobemide or Fluvoxamine, a selective reuptake-inhibitor of 5-HT. The latter belongs to a class of antidepressants known for their better tolerability compared to tricyclic antidepressants. Moclobemide was as effective as Fluvoxamine but much better tolerated as shown by a lower incidence of side effects such as gastrointestinal problems or headache.

Motor strategies in lifting movements: a comparison of adult and child performance.

The experiment compares the performances of children six to nine years old and adults in a simple, monoarticular lifting task. Overt behaviors, as described by the kinematic features of the movement, do not differ qualitatively in the two groups. The patterns of motor commands, as expressed by the electromyographic recordings, are however strikingly different. Adults plan the movement with a careful balance between agonist muscle activity and passive, viscoelastic forces, whereas children use both agonist and antagonist active forces. It is argued that the motor strategy adopted by adults depends upon an internal representation of the properties of the motor system and of the size/weight covariation in natural objects, and that this representation is not yet fully developed at nine years of age.