European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
-
Eur Neuropsychopharmacol · Dec 2004
Randomized Controlled Trial Comparative Study Clinical TrialDuloxetine in the acute and long-term treatment of major depressive disorder: a placebo- and paroxetine-controlled trial.
Duloxetine is a balanced and potent dual reuptake inhibitor of serotonin (5-HT) and norepinephrine (NE) that has previously been shown to be effective in the acute treatment of major depressive disorder (MDD). This placebo-controlled study assesses the safety and efficacy of duloxetine (80 or 120 mg/day) and paroxetine (20 mg QD) during an initial 8-week acute phase and subsequent 6-month continuation phase treatment of MDD. ⋯ These data support previous findings that duloxetine is safe, efficacious, and well tolerated in the acute treatment of MDD. Furthermore, these data provide the first demonstration under double-blind, placebo-controlled conditions that the efficacy and tolerability of duloxetine are maintained during chronic treatment.
-
Eur Neuropsychopharmacol · Dec 2004
Acute effect of milnacipran on the relationship between the locus coeruleus noradrenergic and dorsal raphe serotonergic neuronal transmitters.
The present studies sought to investigate the effect of milnacipran called the serotonin (5-HT) and noradrenaline (NA) reuptake inhibitor (SNRI) on the interaction of central locus coeruleus noradrenergic and dorsal raphe nucleus serotonergic functional activity by utilizing in vivo microdialysis. A single administration of milnacipran (60 mg/kg, s.c.) markedly decreased the levels of NA and its metabolite, 4-hydroxy-3-methoxymandelic acid (HMMA), in the locus coeruleus and the levels of, a metabolite of 5-hydroxytryptamine (5-HT), 5-hydroxyindole-3-acetic acid (5-HIAA) in the dorsal raphe nucleus. Combined administration of yohimbine (2 mg/kg, s.c.),?alpha(2)-adrenoceptor?antagonist, at 2 h after milnacipran (60 mg/kg, s.c.) led to a significant increase in NA levels in the locus coeruleus, although yohimbine alone had no effect on these levels. ⋯ Behavioral signs (locomotion and rearing) were markedly observed following milnacipran alone or combined administration of milnacipran and yohimbine. However, the behavioral signs after coadministration of milnacipran and WAY100635 or NAN-190 were relatively poor. These results may suggest that an increase of NA in the locus coeruleus with the treatment of yohimbine after milnacipran results from negative feedback following the blockade of alpha(2)-adrenoceptors achieved with yohimbine, and that WAY100635 but not NAN-190 recovered milnacipran-induced decrease of 5-HIAA in the dorsal raphe nucleus to control levels by preventing the activation for the presynaptic 5-HT(1A) autoreceptor.