European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
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Eur Neuropsychopharmacol · Jan 2014
Comparative StudyHow well do randomized controlled trial data generalize to 'real-world' clinical practice settings? A comparison of two generalized anxiety disorder studies.
The aim of this post-hoc comparison is to compare efficacy and tolerability results from two generalized anxiety disorder (GAD) studies: a placebo-controlled, randomized controlled trial (RCT) and a study conducted in the clinical practice setting, and to evaluate the extent to which results from RCTs in GAD patients can be generalized to clinical practice. In the clinical practice study, GAD outpatients (n=578) were treated with 4 weeks of pregabalin 150-600mg/day. In the double-blind placebo-controlled RCT, GAD outpatients (n=249) were randomized to 8 weeks of pregabalin (300-600mg/day), or placebo (only the first 4 weeks are included in the current analysis). ⋯ The magnitude of Week 4 improvement on pregabalin in the clinical practice study was numerically larger on the HADS-A (-5.9), VAS-Anxiety (-36.0), MOS-SPI (-22.7), and HADS-D (-5.1), despite use of lower doses. These results suggest that clinical practice patients with GAD may achieve comparable efficacy on lower doses of pregabalin than tested in RCTs, despite having comparable levels of anxiety symptom severity at baseline. The current exploratory comparison also suggests that results from RCTs in patients with GAD may not be directly generalizable to clinical practice.
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Eur Neuropsychopharmacol · Jan 2014
Orcinol glucoside produces antidepressant effects by blocking the behavioural and neuronal deficits caused by chronic stress.
This study focused on the antidepressant potential of orcinol glucoside (OG) and its possible mechanisms of action. We established a depressed rat model using 3 consecutive weeks of chronic unpredictable mild stress (CUMS). The antidepressant-like effect of OG was revealed using the sucrose preference test, the open field test, the forced swimming test (FST), and the tail suspension test (TST). ⋯ Rats that received OG treatment exhibited reduced serum CORT levels and CRH mRNA expression in the hypothalamus, suggesting that the hyperactivity of the HPA axis in CUMS rats was reversed by OG treatment. Moreover, OG treatment upregulated the protein levels of BDNF and phosphorylated-ERK1/2 in the hippocampus, even above control levels. Our findings suggest that OG improved depressive behaviour in CUMS rats by downregulating HPA axis hyperactivity and increasing BDNF expression and ERK1/2 phosphorylation in the hippocampus.
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Eur Neuropsychopharmacol · Jan 2014
Vortioxetine dose-dependently reverses 5-HT depletion-induced deficits in spatial working and object recognition memory: a potential role for 5-HT1A receptor agonism and 5-HT3 receptor antagonism.
We previously reported that the investigational multimodal antidepressant, vortioxetine, reversed 5-HT depletion-induced memory deficits while escitalopram and duloxetine did not. The present report studied the effects of vortioxetine and the potential impact of its 5-HT1A receptor agonist and 5-HT3 receptor antagonist properties on 5-HT depletion-induced memory deficits. Recognition and spatial working memory were assessed in the object recognition (OR) and Y-maze spontaneous alternation (SA) tests, respectively. 5-HT depletion was induced in female Long-Evans rats using 4-cholro-DL-phenylalanine methyl ester HCl (PCPA) and receptor occupancies were determined by ex vivo autoradiography. ⋯ Flesinoxan had a MED ≤1.0mg/kg (∼25% 5-HT1A receptor occupancy; SA); only 1.0mg/kg ameliorated deficits in the NOR. Chronic p.o. vortioxetine administration significantly improved memory performance in OR and occupied 95%, 66%, and 9.5% of 5-HT3, 5-HT1B, and 5-HT1A receptors, respectively. Vortioxetine's effects on SA performance may involve 5-HT1A receptor agonism, but not 5-HT3 receptor antagonism, whereas the effects on OR performance may involve 5-HT3 receptor antagonism and 5-HT1A receptor agonism.