Related Experiment Video
Updated: Aug 20, 2026

The Unpredictable Chronic Mild Stress Protocol for Inducing Anhedonia in Mice
Published on: October 24, 2018
A comparative study of milnacipran and paroxetine in outpatients with major depression
Daniel Sechter1, Pierre Vandel, Emmanuel Weiller
1Service de Psychiatrie de l'Adulte, Centre Hospitalier Universitaire St Jacques, Besançon, Cedex F-25030, France. daniel.sechter@ufc-chu.univ-fcomte.fr
Background:
Milnacipran is a dual-action antidepressant which inhibits both serotonin and noradrenaline reuptake with no affinity for any neurotransmitter receptor studied.
Methods:
A 6-week double-blind multicentre study compared milnacipran (100 mg/day) with paroxetine (20 mg/day) in 300 outpatients with major depression. Efficacy was evaluated using HAMD17, MADRS and CGI for severity of illness and global improvement. Data were analysed on an intention to treat, last observation carried forward, basis.
Results:
Milnacipran and paroxetine were both effective and well tolerated with no significant difference in their effects. After treatment discontinuation, milnacipran was associated with significantly less emergent symptoms. Responders, at endpoint, to milnacipran had significantly greater levels of psychomotor retardation at baseline than non-responders.
Limitations:
The study did not include a placebo group so that it is impossible to determine absolute levels of efficacy.
Conclusions:
Both milnacipran and paroxetine were effective and well tolerated by outpatients with major depression treated for 6 weeks. After treatment discontinuation milnacipran was associated with less emergent symptoms. Psychomotor retardation at baseline may be a predictive factor of a favourable response to milnacipran.