desvenlafaxine-succinate and Bipolar-Disorder

The effects of genetic variants in genes encoding the target structures of antidepressants on the therapeutic efficacy of antidepressant drugs have been investigated with unconclusive results. One possible confounding factor in most studies was the fact that drug serum concentrations had not been determined.. Within a clinical setting, 56 inpatients suffering from depressive episodes in the context of either major depressive disorder or bipolar affective disorder were studied. Response to venlafaxine was assessed after 4 weeks of treatment and correlated to serum concentration and functional variants in genes encoding the norepinephrine (SLC6A2; rs28386840) and the serotonin transporter (SLC6A4; [5-HTTLPR], rs25531). Symptom change was evaluated using the Clinical Global Impression-Improvement (CGI-I) scale.. No association between therapeutic response, venlafaxine serum concentration (active moiety) and rs28386840 was found. In carriers of the high expressing SLC6A4 genotype (lAlA-), a poor response to venlafaxine was found significantly more often. In subsamples stratified for serum concentration this held true for patients with serum concentrations between 201 and 400 ng/mL (n=21), while in patients with sub- (≤ 200 ng/mL; n=12) and supra-recommended (> 400 ng/mL; n=23) concentrations, no significant differences were observed.. The observed association is consistent with findings of some previous studies, whereas others showed differing results highlighting the need for further investigations.

Topics: Adolescent; Adult; Aged; Alleles; Antidepressive Agents; Bipolar Disorder; Cyclohexanols; Depressive Disorder, Major; Desvenlafaxine Succinate; Female; Genotype; Humans; Male; Middle Aged; Norepinephrine Plasma Membrane Transport Proteins; Polymorphism, Genetic; Selective Serotonin Reuptake Inhibitors; Serotonin Plasma Membrane Transport Proteins; Venlafaxine Hydrochloride; Young Adult

Venlafaxine, a serotonin-norepinephrine reuptake inhibitor antidepressant, is metabolized primarily by the cytochrome P450 2D6 enzyme into O-desmethylvenlafaxine (ODV). The ODV/venlafaxine ratio can be used to distinguish between extensive metabolizers (EMs) and poor metabolizers (PMs).. To determine the relative efficacy and tolerability of venlafaxine in EM vs PM patients with major depressive disorder (MDD).. Data from 4 double-blind, placebo-controlled studies of patients with MDD were pooled. Blood samples were analyzed for plasma concentrations of venlafaxine, ODV, total venlafaxine + ODV, and ODV/venlafaxine ratio. Patients were classified as EMs or PMs on the basis of ODV/venlafaxine ratios. Changes from baseline in depression scale scores were compared between EMs and PMs using t tests. Rates of response, remission, discontinuation, and adverse events (AEs) were compared for EMs and PMs using Fisher exact tests.. Compared with PMs, EMs had significantly greater mean changes from baseline on 4 of 5 depression rating scales (all 4 comparisons, P ≤ .020). A significantly greater percentage of EMs achieved response or remission by most measures compared with PMs (4 of 5 comparisons, P ≤ .015). Rates of discontinuation and AEs did not differ significantly between EMs and PMs. Since there were no substantial differences between EMs and PMs in terms of venlafaxine dose or tolerability, these factors are not likely to account for the efficacy findings.. Venlafaxine treatment in EMs was associated with greater efficacy in MDD on virtually all measures compared with PMs, with no important tolerability differences.

Topics: Adolescent; Adult; Aged; Bipolar Disorder; Cyclohexanols; Cytochrome P-450 CYP2D6; Desvenlafaxine Succinate; Double-Blind Method; Female; Humans; Male; Middle Aged; Phenotype; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Treatment Outcome; Venlafaxine Hydrochloride; Young Adult

To assess in a large naturalistic sample, whether clinical response to a treatment with venlafaxine is associated with different patterns of plasma concentrations of active moiety, AM (sum of venlafaxine (VEN) and its active metabolite O-desmethylvenlafaxine (ODVEN)).. Applying a regression model, plasma concentrations and plasma concentrations corrected-by-dosage (C/D) for AM were included as independent variable with Clinical Global Impressions-Improvement (CGI-I) scale ratings as dependent variable. Moreover, AM, VEN, and ODVEN were compared between treatment responders and non-responders, defining response as much or very much improved on the CGI-I scale based on the non-parametric Mann-Whitney U (M-W-U) test with a significance level of 0.05.. No correlations were found between AM and C/D AM plasma concentrations and CGI-I ratings (regression coefficient 0.0, CI 0.000, 0.001, p = 0.492 for AM and 0.047, CI - 0.065, 0.159, p = 0.408 for C/D AM). Venlafaxine daily dosage did not differ between responders and non-responders (217.7 ± 76.9 vs. 222.0 ± 72.7 mg/day, p = 0.45 for M-W-U). Responders displayed lower ODVEN (p = 0.033) and AM (p = 0.031) plasma concentrations than non-responders (p = 0.033 and 0.031, respectively for M-W-U). No other differences were detected. Using a cut-off level of 400 ng/mL for AM concentrations, a higher percentage of responders was reported in the group of patients with AM < 400 ng/mL (13.04%) compared to patients with AM > 400 ng/mL (8%) (p = 0.038).. Higher ODVEN and AM concentrations in non-responders than in responders indicate that treatment escalation above upper thresholds of therapeutic reference ranges of venlafaxine is not promising. Hence, the therapeutic reference range for venlafaxine can help in improving outcomes in a measurement-based care model that takes advantage of therapeutic drug monitoring.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bipolar Disorder; Databases, Factual; Desvenlafaxine Succinate; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Retrospective Studies; Schizophrenia; Serotonin and Noradrenaline Reuptake Inhibitors; Treatment Outcome; Venlafaxine Hydrochloride; Young Adult

Topics: Adult; Antidepressive Agents; Bipolar Disorder; Desvenlafaxine Succinate; Female; Humans; Recurrence

A case is presented of the occurrence of an episode of mania apparently induced by desvenlafaxine, in a patient with a history of major depressive disorder and no apparent history of previous mania or hypo-mania. To our knowledge, this is the first such documented case with this new antidepressant. The discussion focuses on the concept of the bipolar spectrum, and how to view patients who have only become manic while taking antidepressants.

Topics: Antidepressive Agents; Bipolar Disorder; Cyclohexanols; Depressive Disorder, Major; Desvenlafaxine Succinate; Humans; Male; Middle Aged