The international journal of neuropsychopharmacology
-
Int. J. Neuropsychopharmacol. · Apr 2012
Review Meta AnalysisEfficacy of agomelatine in major depressive disorder: meta-analysis and appraisal.
Agomelatine is the first approved antidepressant that mediates its activity through the melatoninergic pathway rather than the monoaminergic system. This meta-analysis aims to summarize an up-to-date report on the efficacy of agomelatine in major depressive disorder. Archives of published results in PubMed, CINAHL, Cochrane Library, EMBASE and PsycINFO databases were searched for randomized double-blind trials comparing agomelatine against placebo or antidepressant in major depressive disorder. ⋯ There were nine trials involving 3943 severe cases of depression on agomelatine (n=2390) and either placebo (n=689) or antidepressants (n=864). Agomelatine (n=1274) stood superior to placebo (n=689) by a small margin (SMD -0.26, p=3.48×10-11) and the superiority of agomelatine (n=834, dose ≥ 25 mg/d) over antidepressants (paroxetine, fluoxetine, sertraline, venlafaxine; n=864) was even smaller (SMD -0.11, p=0.02). Although there is evidence of the superiority of agomelatine over placebo and selected antidepressants, it is questionable whether the magnitude of effect size is clinically significant and sample characteristics are relevant to the general patient population with major depressive disorder.
-
Int. J. Neuropsychopharmacol. · Apr 2012
Serotonin-2C receptors in the basolateral nucleus of the amygdala mediate the anxiogenic effect of acute imipramine and fluoxetine administration.
A growing body of evidence indicates that facilitation of serotonin-2C receptor (5-HT2CR)-mediated neurotransmission in the basolateral nucleus of the amygdala (BLA) is involved in anxiety generation. We investigated here whether BLA 5-HT2CRs exert a differential role in the regulation of defensive behaviours related to generalized anxiety (inhibitory avoidance) and panic (escape) disorders. We also evaluated whether activation of BLA 5-HT2CRs accounts for the anxiogenic effect caused by acute systemic administration of the antidepressants imipramine and fluoxetine. ⋯ Intra-BLA injection of a sub-effective dose of SB-242084 fully blocked the anxiogenic effect caused either by the local microinjection of 5-HT or the systemic administration of imipramine and fluoxetine. Our findings indicate that 5-HT2CRs in BLA are selectively involved in the regulation of defensive behaviours associated with generalized anxiety, but not panic. The results also provide the first direct evidence that activation of BLA 5-HT2CRs accounts for the short-term aversive effect of antidepressants.