The objective of this study was to assess the efficacy, safety, and tolerability of desvenlafaxine (administered as desvenlafaxine succinate) 50 and 100 mg/day for major depressive disorder (MDD). A multicenter, randomized, double-blind, placebo-controlled trial was conducted in Europe and South Africa. Outpatients with MDD received fixed-dose desvenlafaxine (50 or 100 mg/day) or placebo for 8 weeks. The primary efficacy variable was the 17-item Hamilton Rating Scale for Depression total score; secondary measures included Clinical Global Impressions-Improvement scores. The intent-to-treat population included 483 patients: desvenlafaxine 50 mg (n=164), desvenlafaxine 100 mg (n=158), and placebo (n=161). At the last-observation-carried-forward analysis (final evaluation) using analysis of covariance, adjusted mean changes from baseline on the Hamilton Rating Scale for Depression were significantly greater for both desvenlafaxine 50 mg (-13.2; P=0.002) and 100 mg (-13.7; P<0.001) versus placebo (-10.7). Significant differences on the Clinical Global Impressions-Improvement scores were observed for desvenlafaxine 50 mg (P=0.002) and 100 mg (P<0.001) versus placebo. Both doses of desvenlafaxine were generally well tolerated. The most common treatment-emergent adverse events were nausea, dizziness, insomnia, constipation, fatigue, anxiety, and decreased appetite. Fixed doses of desvenlafaxine 50 and 100 mg/day are safe, generally well tolerated, and effective at a clinically relevant level for the treatment of MDD.
Escitalopram is the S-enantiomer of citalopram. In this study, we compared the efficacy of equivalent dosages of escitalopram and citalopram in the treatment of moderate to severe major depressive disorder (MDD), based on data from two, pooled, randomized, double-blind, placebo-controlled studies of escitalopram in which citalopram was the active reference. The primary efficacy parameter was the mean change from baseline in the Montgomery Asberg Depression Rating Scale (MADRS) total score. Significant differences in favour of escitalopram were observed for the MADRS [P<0.05, observed cases (OC)/last observation carried forward (LOCF)] and Clinical Global Improvement-Severity of Illness scores (CGI-S; P<0.05, OC/LOCF). Escitalopram separated from placebo at week 1 on the primary efficacy parameter, whereas citalopram first separated from placebo at week 6. An analysis of time to response showed that escitalopram-treated patients responded significantly faster to treatment than citalopram-treated patients (P<0.01). More patients responded to and achieved remission with escitalopram than to citalopram (P<0.05, OC). The HAMD scale was only used in the fixed-dose study, where escitalopram-treated patients had a significant reduction in HAMD-17 total score at week 8 compared to citalopram-treated patients (P<0.05, OC/LOCF). In the pooled subpopulation of severely ill patients (MADRS> or = 30), escitalopram-treated patients showed greater improvement than citalopram-treated patients (P<0.05, LOCF/OC). Escitalopram showed consistently superior efficacy compared to citalopram in the treatment of moderate to severe MDD on all efficacy parameters, and was similarly well tolerated.
Data obtained from animal and human brain imaging studies indicate that frontal cortex and medial temporal lobe are involved in experiencing and controlling fear and anxiety. We tested the hypothesis that benzodiazepine receptor binding is decreased in the left temporal pole and increased in the right prefrontal area among patients suffering from anxiety. We studied 10 drug-naive female patients with generalized anxiety disorder (GAD) and 10 age-and gendermatched healthy controls with MRI and with SPET by using a new 123 I-labelled specific benzodiazepine receptor radioligand, NNC 13-8241. Blindly analyzed results showed that the benzodiazepine receptor binding of [ 123 I]NNC 13-8241 was significantly decreased in the left temporal pole among patients with GAD when compared with age-and sex-matched healthy controls. This hemispheric asymmetry was studied further with a fractal analysis of the SPET images. The fractal dimension of the left hemispheric benzodiazepine receptor binding in patients with GAD was significantly higher than that of controls (1.28 ± 0.09 and 1.17 ± 0.07, respectively), whereas the intercept was decreased by 43 ± 23% reflecting more homogeneous cerebral benzodiazepine receptor density distribution in patients with GAD. The finding is analogous to the decreased heterogeneity of myocardial blood flow observed in patients with ischemic heart disease. The results are consistent with the general hypothesis that high regional heterogeneity of perfusion, metabolism and receptor density is necessary to maintain adaptation ability in the living organism.
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