ClinicalTrials identifier: NCT00788944.

Compulsive buying is a syndrome characterized by the impulsive and/or compulsive buying of unneeded objects that results in personal distress, impairment in vocational or social functioning, and/or financial problems. Results from a two-site, double-blind, placebo-controlled 13-week trial of fluvoxamine are presented. Subjects had problematic buying behavior that they could not control for the previous 6 months or longer and met DSM-IV criteria for impulse control disorder-not otherwise specified (ICD-NOS) and the University of Cincinnati criteria for compulsive buying. Assessments included clinician-rated scales-the Yale-Brown Obsessive Compulsive Scale modified for compulsive buying, the Clinical Global Impression Scale, the Global Assessment of Functioning, and the Hamilton Rating Scale for Depression-and patient self-reports using daily diaries, which measured episodes of compulsive buying. Forty-two subjects gave informed consent, with 37 subjects providing evaluable information and 23 completing the study. Current or past psychiatric comorbidity was present in 74% of subjects. Intent-to-treat and completer analyses failed to show a significant difference between treatments on any measures of outcome. A high placebo-response rate, possibly from the behavioral benefits of maintaining a daily diary, prevents any definitive statement on the efficacy of fluvoxamine in treating compulsive buying.

In contrast to venlafaxine ER 75  mg, the pharmacokinetics of desvenlafaxine 50  mg is not significantly impacted by CYP2D6 genetic polymorphisms. PMs receiving venlafaxine ER 75  mg had significantly lower O-desmethylvenlafaxine and higher venlafaxine plasma concentrations.

Among postmenopausal outpatients with MDD, there were no significant differences in the efficacy of desvenlafaxine and escitalopram based on primary efficacy analyses. The results do not support the overall hypothesis that the serotonin-norepinephrine reuptake inhibitor desvenlafaxine has an efficacy advantage for the treatment of MDD in postmenopausal women because, in this particular subgroup, desvenlafaxine failed to prove superiority over escitalopram. Safety and tolerability were comparable.

Background: This series of experiments was conducted to describe the metabolic profile of the serotoninnorepinephrine reuptake inhibitor desvenlafaxine (administered as desvenlafaxine succinate) using animal and human models. Methods: In vivo and in vitro experiments were conducted with humans and preclinical species (CD-1 mice, Sprague Dawley rats, and beagle dogs). Single oral doses of [ 14 C]-desvenlafaxine were administered to each preclinical species for analyses of desvenlafaxine concentration in plasma, urine, and feces. Rats also were subjected to whole body autoradiography and quantitative tissue sampling. The major UDP-glucuronosyltransferase (UGT) isoforms involved in the formation of desvenlafaxine-O-glucuronide were also assessed. In vivo human experiments were conducted with healthy volunteers administered desvenlafaxine 100, 300, or 600 mg, followed by 72 hours of plasma sampling. In vitro experiments were conducted with human and animal liver microsomes and human hepatocytes to determine the effect of desvenlafaxine on cytochrome P450 (CYP) enzyme activity. Desvenlafaxine concentrations were measured using high performance liquid chromatography and liquid chromatography/mass spectrometry methods. Results: The primary metabolic pathways for desvenlafaxine included glucuronidation, oxidation, and N-demethylation. In humans, desvenlafaxine was the predominant drug-related species in plasma and urine. However, in mice, rats, and dogs, desvenlafaxine-O-glucuronide was the most commonly detected in plasma and urine. Urine was the primary route of excretion of desvenlafaxine in all species. Multiple UGTs were capable of desvenlafaxine metabolism. Oxidative metabolism via the CYP3A4 was a minor contributor to desvenlafaxine metabolism; however, desvenlafaxine did not induce or inhibit CYP3A4 activity. Desvenlafaxine did not act as a significant mechanism-based inhibitor of the assessed CYP isoenzymes. Conclusion: These findings support other study results suggesting that desvenlafaxine has a simple metabolic profile. Desvenlafaxine is unlikely to contribute to clinically significant CYP-mediated drug-drug interactions. The relatively simple metabolic profile of desvenlafaxine may lead to clinical benefits in those patients being treated for major depressive disorder.