No abstract

A multicenter study compared the antidepressant efficacy and the tolerance of two doses of milnacipran (50 mg and 100 mg/day) and amitriptyline (150 mg/day) in three parallel groups of 45 major depressive inpatients defined by Research Diagnostic Criteria. After a wash-out period of 4-7 days on placebo with lorazepam and/or nitrazepam if necessary, patients were randomly assigned to a daily dose of milnacipran 50 mg, milnacipran 100 mg or amitriptyline 150 mg reached on the 5th day and then stable over a 4-week period, with weekly assessments by means of the Montgomery and Asberg depression scale, the Hamilton depression scale, the Clinical Global Impressions (CGI) and the Target Emergent Signs and Symptoms. Results showed significant superiority of both milnacipran 100 mg/day and amitriptyline over milnacipran 50 mg/day at the end of the treatment period. However, amitriptyline induced a nonsignificant trend toward more rapid improvement after 2 weeks of treatment, mainly based on items related to insomnia, supporting more sedative properties of amitriptyline as compared to milnacipran. Anticholinergic side-effects were significantly lower with milnacipran than with amitriptyline, explaining why milnacipran 100 mg exhibited at the end of the treatment period, a nonsignificantly better efficacy index on the CGI. Moreover, in contrast to milnacipran, amitriptyline was responsible for a significant decrease in blood pressure and a significant weight gain.

Fifty-eight inpatients with a DSM-III diagnosis of major depressive disorder participated in a 5-week double-blind trial of milnacipran and placebo. Milnacipran was superior to placebo on all measures of depression. The first index of milnacipran superiority was the difference of dropouts due to treatment failure between milnacipran (10.3%) and placebo (55.2%). All patients were evaluated up to day 14. The improvement with milnacipran was statistically significant at day 14. Side effects were identical for milnacipran and placebo.

A multicentre study compared the antidepressant efficacy and the tolerance of milnacipran (200 mg/d) and amitriptyline (1 50 mg/d) in two parallel groups of 43 major depressive inpatients, endogenous subtype, as defined by Research Diagnostic Criteria. The duration of the study was 4 weeks, with weekly assessments by means of the Montgomery and Asberg depression scale (MADS), the Hamilton depression scale, the Clinical Global Impressions (CGI) and a checklist of symptoms and side-effects. Results showed similar improvement in both groups but better tolerance with milnacipran (less drowsiness and anticholinergic side-effects), reflected in the better scores on the therapeutic index of the CGI. The clinical profile of the two drugs was somewhat different with more transitory sedation with amitriptyline and more improvement in concentration difficulties with milnacipran during the first weeks of the study associated with more effect on retardation with milnacipran at the end of the study.

RésuméLa transposition de la directive 2001/20/CE relative aux bonnes pratiques cliniques dans la conduite des essais de médicaments à usage humain a nécessité la modification de certaines dispositions du droit français en matière de protection des personnes se prêtant à des recherches biomédicales, notamment celles relatives aux conditions d'autorisation des recherches biomédicales. Le régime déclaratif à l'autorité compétente antérieur devient un régime d'autorisation préalable, et l'avis préalable d'un comité de protection a désormais la nécessité d'être expressément favorable pour que l'essai soit mis en oeuvre. Des propositions sont formulées par cette table ronde afin de favoriser la stabilité et le professionnalisme des Comités de Protection des Personnes (CPP).