Controlled comparison of milnacipran and fluoxetine in major depression

Abstract

The efficacy and the tolerance of milnacipran (100 mg/day), a second generation antidepressant which equipotently inhibits both noradrenaline and serotonin reuptake, was compared to fluoxetine (20 mg/day), a selective serotonin reuptake inhibitor, in two parallel groups of, respectively, 97 and 93 major depressive outpatients. The duration of the study was 6 weeks, with assessments every 2 weeks by means of the Montgomery and Asberg depression scale (MADRS), the Hamilton depression scale, the clinical global impressions (CGI), and a checklist of symptoms and side-effects. Results showed significant superiority of fluoxetine over milnacipran on most rating instruments: MADRS (P = 0.01) including five individual items, Hamilton depression scale (P = 0.002) including ten individual items, CGI of severity (P = 0.01) and therapeutical index (P = 0.002). On visual analogue scales assessing the clinical profile of the compounds, fluoxetine was rated as exhibiting more psychostimulating activity than milnacipran (P = 0.0008). The tolerance of the two antidepressants was very similar, with the exception of symptoms of dizziness which were more frequently reported with milnacipran (P = 0.01). These differences in efficacy favoring fluoxetine could result from the selection of a dose of milnacipran below the optimal therapeutic dose for this type of psychiatric patients or to the administration of the compounds in single daily intakes, whereas milnacipran possesses a plasma elimination half-life of only 7 h.

A eficácia do milnaciprano em pacientes ambulatoriais com transtorno depressivo maior não respondedores ao tratamento com ISRSs: um estudo aberto de 12 semanas

“…Most of them show no difference in efficacy [15][16][17][18] . One study show an SSRI (fluoxetine) with more efficacy than minalcipran 19 , while another the opposite 11 . A recent meta-analysis 20 concluded that milnacipran and SSRIs do not differ with respect to the overall efficacy in the treatment of MDD.…”

Antidepressants are selective serotonin neuronal reuptake inhibitors: 40-year history

“…В 1994 г. бельгийские иссле-дователи обследовали 190 больных, страдающих «большой депрессией». Авторы пришли к заключению, что 6-недель-ная терапия флуоксетином (20 мг/сут) более эффективна, чем применение милнаципрана (100 мг/сут) [22]. Француз-ские психиатры в 1998 г. провели исследование на материа-ле 289 больных эндогенной депрессией.…”

Conformational Analysis of the NMDA Receptor Antagonist (1S,2R)-1-Phenyl-2-[(S)-1-aminopropyl]-N,N-diethylcyclopropanecarboxamide (PPDC) Designed by a Novel Conformational Restriction Method Based on the Structural Feature of Cyclopropane Ring.

“…[4][5][6][7][8] In fact, cyclopropane rings have already been successfully used to restrict the bioactive conformations of neurotransmitters, 4,5) amino acids, 6) peptides 7) and nucleosides. 8) We devised a new method for restricting the conformation of compounds having a cyclopropane ring, [9][10][11] and applied it to the design of the conformationally restricted analogs of [12][13][14][15][16] a clinically efficient antidepressant having a cyclopropane structure, to develop efficient NMDA (N-methyl-D-aspartic acid) receptor antagonists. [17][18][19][20][21][22][23][24][25] The structures of the conformationally restricted analogs are shown in Fig.…”

“…Design and Pharmacological Effect of PPDC Milnacipran, which shows a potent antidepressant effect due to competitive inhibition of the re-uptake of serotonin (5-HT) in the central nervous system (CNS), [12][13][14][15][16] is also recognized as a non-competitive NMDA receptor antagonist. 35) Although the binding affinity of (Ϯ)-1 for the NMDA receptor is not high, the compound has the advantage of sufficiently pene- trating into the brain without serious side effects, 15,16) making it a clinically useful antidepressant and therefore a good lead for an efficient NMDA receptor antagonist.…”

“…35) Although the binding affinity of (Ϯ)-1 for the NMDA receptor is not high, the compound has the advantage of sufficiently pene- trating into the brain without serious side effects, 15,16) making it a clinically useful antidepressant and therefore a good lead for an efficient NMDA receptor antagonist. This may be because the structure of milnacipran is clearly different from that of previous NMDA receptor antagonists.…”