Controlled comparison of two doses of milnacipran (F 2207) and amitriptyline in major depressive inpatients

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.

Antidepressant behavioral effects by dual inhibition of monoamine reuptake in the rat forced swimming test

“…Another common characteristic of these drugs is their relatively weak a¦nity for muscarinic, histaminergic, dopaminergic, serotonergic, and a-adrenergic receptors (Moret et al 1985;Muth et al 1986;Wong et al 1993), which may account for fewer undesirable adverse e¤ects than observed with many tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors. Clinical studies have shown that venlafaxine (Schweizer et al 1991(Schweizer et al , 1994Mendels et al 1993) and milnacipran (Ansseau et al 1989;Macher 1989) are at least as e¤ective as TCAs or SSRIs in treating major depressive disorder. At higher doses, these drugs have been reported to produce more rapid therapeutic e¤ects than tricyclics (Serre et al 1986;Derivan et al 1995), although caution is advised when evaluating the time-course for clinical e¦cacy of di¤erent antidepressants.…”

The effects of serotonin and/or noradrenaline reuptake inhibitors on impulsive-like action assessed by the three-choice serial reaction time task: a simple and valid model of impulsive action using rats

“…In the present study, we examined the effects of milnacipran, a serotonin/noradrenaline reuptake inhibitor, on impulsive-like action. Given that the beneficial effect of milnacipran against depression has been established (Ansseau et al, 1989) and that this drug increases both serotonin and noradrenaline in the synaptic cleft (Stahl et al, 2005;Tachibana et al, 2006), it may greatly improve impulse control.…”

Milnacipran: The Clinical Properties of a Selective Serotonin and Noradrenaline Reuptake Inhibitor (SNRI)

“…Hence these agents are potentially lethal when taken in overdose, either intentionally or accidentally. A four week study involving 135 patients compared milnacipran (25 mg and 50 mg bid) with amitriptyline (75 mg bid) in the treatment of in-patients with major depression (Ansseau et al, 1989). The 50 mg bid dose of milnacipran was as eective as amitriptyline in terms of improvements in HDRS, MADRS and CGI scores, as well as having a more favourable tolerability pro®le.…”