Milnacipran and venlafaxine at flexible doses (up to 200 mg/day) in the outpatient treatment of adults with moderate-to-severe major depressive disorder: a 24-week randomized, double-blind exploratory study

Abstract

The objective of this exploratory, multicenter, randomized, double-blind study, was to evaluate the efficacy and safety/tolerability of milnacipran and venlafaxine administered at flexible doses (100, 150 or 200 mg/day, bid administration) for 24 weeks (including 4 weeks up titration period) in the outpatient treatment of adults presenting with a moderate or severe episode of major depressive disorder (MDD) without high suicidal risk (MINI-DSM IV-TR). Of the 195 patients included, 134 (68.7%) completed the study. At baseline the two groups were similar, except there was a higher proportion of patients whose episode was severe-DSM IV in the milnacipran group (63.3% versus 54.0% in the venlafaxine group). The initial MADRS score (mean 31.0) decreased progressively during the study, and this decrease was in the two treatment groups (n = 177: 90 milnacipran; 87 venlafaxine) at week 24 (observed case/OC, mean change −23.1 milnacipran; −22.4 venlafaxine). The rate of MADRS response (reduction ≥ 50%) at week 8 and week 24-last observation carried forward/LOCF was similar in the two groups (week 8: 64.4% milnacipran; 65.5% venlafaxine; week 24: 70% milnacipran; 77% venlafaxine), as was the rate of MADRS remission (score ≤ 10) (week 8: 42.2% milnacipran; 42.5% venlafaxine; week 24: 52.2% milnacipran; 62.1% venlafaxine). In both groups, the most common adverse events were: nausea, dizziness, headache, hyperhidrosis and, in males, genito-urinary problems. The overall safety/tolerability and efficacy profiles of milnacipran and venlafaxine administered at flexible dosages (up to 200 mg/day) were similar in the long term treatment of adults during episodes of MDD in an outpatient setting.

Keywords:

• major depressive episode
• adult
• serotonin and norepinephrine reuptake inhibitors
• milnacipran
• venlafaxine

Acknowledgements

The authors would like to thank the investigating psychiatrists:

M Abbar (30006 Nîmes), I Amado (75074 Paris), J Audet* (16000 Angoulême), GP Badet (21033 Dijon), B Baranovski* (35000 Rennes), R Benadhira (93200 Saint-Denis), B Bonin (21033 Dijon), F Boulet (30006 Nîmes), C Bourbon* (31400 Toulouse), P Bourgoin* (16000 Angoulême), Y Caer (30006 Nîmes), M Cazenave (33076 Bordeaux), N Chapel (13274 Marseille), F Chapelle* (31300 Toulouse), JC Chauvet-Gelinier (21033 Dijon), G Collin (34295 Montpellier), P Courtet (34295 Montpellier), R Didi (21033 Dijon), W De Carvalho (75116 Paris), D Drapier (35703 Rennes), J Farisse (13274 Marseille), M Faure* (37000 Tours), G Fischman (75005 Paris), C Gaussares* (33120 Arcachon), C Géraud* (53200 Château-Gontier), GC Girod (21033 Dijon), R Gourevitch (75074 Paris), JM Guibaud* (31200 Toulouse), B Kastler (67091 Strasbourg), D Januel (93200 Saint-Denis), Pr F Juan (44035 Nantes), Pr C Lancon (13274 Marseille), F Lanvin* (59139 Wattignies), P Leclercq* (68100 Mulhouse), N Le Garzic (35703 Rennes), P Le Goubey* (50100 Cherbourg), T Loiseau* (78500 Sartrouville), Pr B Millet (35703 Rennes), D Modavi (31200 Toulouse), R Mhiri* (78230 Le Pecq), E Neuman* (78230 Le Pecq), N Parant-Lucena* (31000 Toulouse), M Patris (67091 Strasbourg), J Pon* (31200 Toulouse), S Torres (34295 Montpellier), B Trojak (21033 Dijon), JM Vanelle (44035 Nantes), A Viala (75674 Paris).

*Members of the group GICIPI (Groupe d’investigateurs cliniciens indépendants pour des études pivotales de qualité [Group of independent clinical investigators for quality pivotal studies]).

A report of this study has been published in French.²²

The study was sponsored by Pierre Fabre Médicament, manufacturers of milnacipran.

Disclosures

AM and MR are employees of Pierre Fabre Médicament.