[RÉALITÉ LT, a pharmacoepidemiological study of semiology and therapeutic strategy of patients with schizophrenia treated by antipsychotic loxapine in routine clinical practice]. / RÉALITÉ LT : Recherche Épidémiologique sur l'Activité de la Loxapine et ses Indications en Thérapeutique quotidiennE lors d'une utilisation à Long Terme. Étude pharmacoépidémiologique : sémiologie et stratégie thérapeutique d'une population de patients présentant des troubles schizophréniques traités par loxapine.

INTRODUCTION: Data concerning the clinical and therapeutic characteristics of patients with schizophrenia treated by antipsychotic in naturalistic conditions are useful. Two national pharmacoepidemiological studies were conducted in France, a retrospective survey RÉALITÉ and a prospective study RÉALITÉ LT, to examine the use of loxapine, first in acute and chronic psychotic states and second in long-term treatment prescribed for patients with schizophrenia. AIM OF STUDY: The aim of RÉALITÉ LT is to specify the clinical characteristics of schizophrenic patients treated by loxapine for at least 4 months and the description of the methods of use of this antipsychotic medication during a 6-month follow-up in "real life" conditions. DESIGN OF STUDY: RÉALITÉ LT is an epidemiologic, observational, longitudinal, prospective (during a half-year period), multicenter and national study of the prescription of loxapine in routine clinical practice. For this study, 645 patients with schizophrenia treated by loxapine were recruited, assessed by PANSS, CGI, GAF, MeDra-SOC-PT for side effects and Girerd questionnaire for compliance; statistical analysis used SAS 9.2. RESULTS: Six hundred and forty-five adult patients were included and assessed at inclusion, month 3 and 6. These patients were mostly male (69%), with an average age of 41, inactive (68%), lonely with no child (79%), under psychiatric care for more than 5 years (81%), less than one third were inpatients. The subtypes of schizophrenia were paranoid (59%), disorganised (21%), undifferentiated or residual (10%), the outcome of psychotic illness was episodic (50%) or continuous (33%). The daily mean dosage of loxapine was 168,4 mg/d, in antipsychotic loxapine monotherapy (27%) or in combination with other antipsychotics (63%); it was often associated with psychotropic medications (anxiolytic [72%], antidepressant [21%], normothymic [19%]). The stability of the dosage of loxapine during the 6 months follow-up (60%) was associated with strict loxapine monotherapy or antipsychotic monotherapy (loxapine associated with other psychotropic medication). Safety, side effects and compliance were compared with previous studies. DISCUSSION AND CONCLUSION: These results are discussed, comparing the two pharmacoepidemiological studies RÉALITÉ and RÉALITÉ LT, loxapine is used in compliance with the two indications (smpc) and French guidelines (HAS, Haute Autorité de santé).

A double-blind comparison of the efficacy and safety of milnacipran and fluoxetine in depressed inpatients.

This double-blind, randomised, multicentre study compared the antidepressant efficacy and safety of two doses of milnacipran (100 mg/day and 200 mg/day) and fluoxetine (20 mg/day) in 289 inpatients with endogenous depression. After a placebo washout period of 4-7 days, assessments were performed weekly during the first 4 weeks, and then after 6, 8 and 12 weeks, using the 17-item Hamilton Depression Rating Scale (HDRS), the Montgomery-Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression (CGI). HDRS total score was reduced by a mean of 14.8 in the milnacipran 100 mg/day group, 12.9 in the milnacipran 200 mg/day group and 12.1 in the fluoxetine 20 mg/day group. MADRS total score decreased by 17.4, 15.8 and 14.6, respectively. No significant difference could be shown between the three treatment groups for either the HDRS or MADRS total scores. However, the time-by-time change showed a trend in favour of milnacipran 100 mg/day, which was found significantly superior to fluoxetine at day 28 for several converging parameters (MADRS, CGI-3). Overall, efficacy ratings for all parameters were highest for milnacipran 100 mg/day, followed by milnacipran 200 mg/day and fluoxetine 20 mg/day. Side-effect profiles were not significantly different between groups except for a significantly greater frequency of dose-related increase in heart rate > or = 100 bpm in milnacipran recipients and a significantly greater weight loss in fluoxetine recipients.

Double-blind study of the efficacy and safety of milnacipran and imipramine in elderly patients with major depressive episode.

The novel antidepressant agent milnacipran is a dual and equipotent serotonin and noradrenaline reuptake inhibitor. The aim of this double-blind study was to compare the efficacy and safety of milnacipran (50 mg twice daily) with that of imipramine (50 mg twice daily) in elderly patients with major depressive episode. A total of 219 patients were randomly assigned to 8 weeks of double-blind treatment with either milnacipran or imipramine; 72 patients withdrew from the study. At the end of treatment no significant differences were found between milnacipran and imipramine in antidepressant efficacy. A significantly greater number of side-effects, particularly anticholinergic effects, was observed in the imipramine group. Milnacipran may be preferable to imipramine in elderly depressed patients, as it provides the same antidepressant activity as imipramine with a lower incidence of side-effects, and does not impair cognitive ability.

[Plasma tryptophan in a protein controlled diet in depressed patients]. / Tryptophane plasmatique à apport protéique contrôlé chez des déprimés.

Cerebral serotonin is synthetized from its blood precursor: tryptophan (TRP), an essential amino acid (6). TRP has been extensively studied since serotonine has been reported to be involved in the pathogenesis of depression (9). In one hand, brain serotonin content depends on regulation by plasma large neutral amino acids (LNAA): leucine, isoleucine, valine, tyrosine and phenylalanine that compete with TRP to cross over the blood brain barrier (7, 13). In the other hand TRP is largely linked with albumin. So, we have studied plasma total TRP, free TRP and the ratio TRP on LNAA as potential cerebral serotonin index. The aim of this study is to observe the blood variations of the biological parameters in fasting and postprandial conditions in 8 depressed women, aged from 57 to 78 years, on a short protein controlled diet: 4 women had TRP poor then rich diet and the others 4 rich then poor. Alimentary proteins modulated diets and each patient was his own control: the results under modulated diet were compared with those under normal diet at the same time. More over, 2 psychotic patients aged 58 and 70 years have been studied at the same time, in each group. Biological datas were compared with clinical evolution.