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Karen A Tourian - One of the best experts on this subject based on the ideXlab platform.
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pharmacokinetics and tolerability of single ascending doses of Desvenlafaxine administered to children and adolescents with major depressive disorder
Journal of Child and Adolescent Psychopharmacology, 2016Co-Authors: Robert L Findling, Karen A Tourian, James Groark, Sara Ramaker, Deborah Chiles, Lingfeng Yang, Alice I NicholsAbstract:Abstract Objective: To investigate the safety and pharmacokinetic profile of ascending doses of Desvenlafaxine in children and adolescents with major depressive disorder. Assessment of the effect of Desvenlafaxine on depression symptoms was exploratory. Methods: The 8-week, open-label study included an initial 3.5-day inpatient period followed by a 7.5-week outpatient period. Children (7–11 years) received a single Desvenlafaxine dose of 10, 25, 50, or 100 mg on day 1; adolescents (12–17 years) received Desvenlafaxine 25, 50, 100, or 200 mg/day. Plasma and urine samples were collected over the initial 72-hour inpatient period. Evaluations included treatment-emergent adverse events (TEAEs), physical examinations (including Tanner Staging), vital signs, laboratory assessments, 12-lead electrocardiogram, Columbia-Suicide Severity Rating Scale, and the Children's Depression Rating Scale-Revised (CDRS-R). Results: In all, 29 children and 30 adolescents took at least one dose of Desvenlafaxine and were included...
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effects of Desvenlafaxine on blood pressure in patients treated for major depressive disorder a pooled analysis
Current Medical Research and Opinion, 2015Co-Authors: Michael E Thase, Rufong J Cheng, Christine J Guicopabia, Rana Fayyad, Matthieu Boucher, Jonathan Sporn, Karen A TourianAbstract:AbstractObjective:To evaluate the effect of the serotonin-norepinephrine re-uptake inhibitor Desvenlafaxine on blood pressure and incidence of new onset hypertension in pooled short-term studies and in two longer-term, randomized withdrawal studies.Research design and methods:Data from patients randomly assigned to Desvenlafaxine 10 mg to 400 mg/day or placebo in 11 short-term (8–12 weeks), fixed-dose, double-blind, placebo-controlled studies of major depressive disorder (MDD) were pooled for analysis; two Desvenlafaxine randomized withdrawal studies (36 and 46 weeks) were analyzed separately.Clinical trial registration:www.clinicaltrials.gov, NCT00072774, NCT00073762, NCT00277823, NCT00300378, NCT00384033, NCT00798707, NCT00863798, NCT01121484, NCT00824291, NCT01432457, NCT00075257, NCT00887224.Main outcome measures:Outcomes included change from baseline in supine systolic blood pressure (SSBP) and supine diastolic blood pressure (SDBP), assessed using a mixed model repeated measures (MMRM) analysis, and...
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a double blind randomized placebo controlled study assessing the efficacy and tolerability of Desvenlafaxine 10 and 50 mg day in adult outpatients with major depressive disorder
BMC Psychiatry, 2013Co-Authors: Michael R Liebowitz, Karen A Tourian, Eunhee Hwang, Linda MeleAbstract:Background In an effort to establish the lowest effective dose of Desvenlafaxine (administered as Desvenlafaxine succinate), we assessed the efficacy, safety, and tolerability of 10- and 50-mg/day Desvenlafaxine vs placebo for the treatment of major depressive disorder.
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efficacy and safety of Desvenlafaxine 50 mg d for prevention of relapse in major depressive disorder a randomized controlled trial
The Journal of Clinical Psychiatry, 2013Co-Authors: Joshua Z Rosenthal, Cécile Vialet, Eunhee Hwang, Patrice Boyer, Karen A TourianAbstract:Abstract To evaluate the long-term (11-month) efficacy and safety of Desvenlafaxine (administered as Desvenlafaxine succinate) at the recommended 50-mg/d dose in preventing relapse in patients with major depressive disorder (MDD). Adult outpatients (age ≥ 18 years) with MDD (DSM-IV criteria) and a 17-item Hamilton Depression Rating Scale (HDRS17) total score ≥ 20 at screening and baseline were enrolled in a multicenter, double-blind, placebo-controlled, randomized withdrawal trial conducted between June 2009 and March 2011. Patients who responded to 8-week open-label treatment with Desvenlafaxine 50 mg/d with continuing stable response through week 20 were randomly assigned to receive placebo or Desvenlafaxine 50 mg/d in a 6-month, double-blind, randomized withdrawal period. The primary efficacy endpoint was time to relapse following randomization to double-blind treatment, which was compared between groups using the log-rank test. Relapse was defined as HDRS17 total score ≥ 16, discontinuation for unsatisfactory response, hospitalization for depression, suicide attempt, or suicide. Safety and tolerability data were collected throughout the trial. A total of 874 patients were enrolled; 548 patients were randomly assigned to receive placebo (n = 276) or Desvenlafaxine 50 mg/d (n = 272) in the double-blind withdrawal period. Time to relapse was significantly shorter for placebo versus Desvenlafaxine (P
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Efficacy and safety of Desvenlafaxine 25 and 50▒mg/day in a randomized, placebo-controlled study of depressed outpatients.
Journal of Psychiatric Practice, 2013Co-Authors: Nakao Iwata, Karen A Tourian, Eunhee Hwang, Linda Mele, Cécile VialetAbstract:This study evaluated the efficacy and safety of low-dose Desvenlafaxine (administered as Desvenlafaxine succinate) in treating major depressive disorder (MDD). Adult outpatients (aged 18 years) in the United States and (aged 20 years) in Japan, who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for MDD and had a 17-item Hamilton Depression Rating Scale (HAM-D17) score 20, were ran-domly assigned to placebo, low-dose Desvenlafaxine (25▒mg/day), or the recommended dose (50▒mg/day) after a 6to 14-day placebo lead-in, in an 8-week, fixed-dose trial. The primary efficacy variable was change from baseline in HAMD17 total score at final on-therapy evaluation. Efficacy analyses were based on the intent-totreat (ITT) population, using the last observation carried forward. The ITT population included 699 patients. Reduction in HAM-D17 scores from baseline to final evaluation was not significantly greater for Desvenlafaxine 25▒mg/day (-8.98) but was significantly greater for Desvenlafaxine 50▒mg/day (-10.02; P = 0.016) versus placebo (-8.52) after adjusting for multiplicity. P-values were < 0.05 versus placebo for percentage of patients responding to treatment ( 50% decrease in HAM-D17 score) with desven-lafaxine 50▒mg/day (46%; P = 0.015), but not with Desvenlafaxine 25▒mg/day (42% versus 35% with placebo). P-values for remission rates (HAM-D17 score ≤ 7) were not < 0.05 versus placebo for either Desvenlafaxine treatment group. Discontinuations due to adverse events were observed in 2.6%, 3.4%, and 3.4% of patients treated with placebo, Desvenlafaxine 25▒mg/day, and Desvenlafaxine 50▒mg/day, respectively. Consistent with other clinical studies, Desvenlafaxine 50▒mg/day demonstrated antidepressant efficacy and appears to be the minimally effective dosage for MDD. ClinicalTrials study identifier NCT00798707.
Christine J Guicopabia - One of the best experts on this subject based on the ideXlab platform.
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the effect of Desvenlafaxine on cognitive functioning in employed outpatients with major depressive disorder a substudy of a randomized double blind placebo controlled trial
Journal of Psychopharmacology, 2016Co-Authors: Christine J Guicopabia, Sujana Reddy, Rana Fayyad, Chris Edgar, Keith WesnesAbstract:The objective of this substudy was to examine the effect of Desvenlafaxine 50 mg/day compared with placebo on cognitive function in employed outpatients with major depressive disorder. A total of 11/55 (20%) study sites in a 12-week, randomized, double-blind, placebo-controlled trial administered cognitive assessments in memory, attention, and executive functioning domains using the cognitive drug research system. Changes from baseline were subjected to analysis of covariance with baseline levels as covariates, using last observation carried forward data. A significant improvement with Desvenlafaxine 50 mg/day (n=52) compared with placebo (n=29) was observed on the quality of working memory composite measure (0.081 units (0.005, 0.156); P=0.0365) at last observation carried forward. Improvement from baseline on the speed of working memory composite was significant for Desvenlafaxine (−226.6 msec (−316.7, −136.4); P<0.0001) and for placebo (−133.3 msec (−257.2, −9.4); P=0.0354); however, the treatment effe...
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effects of Desvenlafaxine on blood pressure in patients treated for major depressive disorder a pooled analysis
Current Medical Research and Opinion, 2015Co-Authors: Michael E Thase, Rufong J Cheng, Christine J Guicopabia, Rana Fayyad, Matthieu Boucher, Jonathan Sporn, Karen A TourianAbstract:AbstractObjective:To evaluate the effect of the serotonin-norepinephrine re-uptake inhibitor Desvenlafaxine on blood pressure and incidence of new onset hypertension in pooled short-term studies and in two longer-term, randomized withdrawal studies.Research design and methods:Data from patients randomly assigned to Desvenlafaxine 10 mg to 400 mg/day or placebo in 11 short-term (8–12 weeks), fixed-dose, double-blind, placebo-controlled studies of major depressive disorder (MDD) were pooled for analysis; two Desvenlafaxine randomized withdrawal studies (36 and 46 weeks) were analyzed separately.Clinical trial registration:www.clinicaltrials.gov, NCT00072774, NCT00073762, NCT00277823, NCT00300378, NCT00384033, NCT00798707, NCT00863798, NCT01121484, NCT00824291, NCT01432457, NCT00075257, NCT00887224.Main outcome measures:Outcomes included change from baseline in supine systolic blood pressure (SSBP) and supine diastolic blood pressure (SDBP), assessed using a mixed model repeated measures (MMRM) analysis, and...
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an analysis of relapse rates and predictors of relapse in 2 randomized placebo controlled trials of Desvenlafaxine for major depressive disorder
The Primary Care Companion To The Journal of Clinical Psychiatry, 2015Co-Authors: Roger S Mcintyre, Christine J Guicopabia, Rana Fayyad, Matthieu BoucherAbstract:Objective: To evaluate relapse rates and predictors of relapse in 2 randomized, placebo-controlled trials of Desvenlafaxine for major depressive disorder (MDD). Method: Study 1: week 8 responders to open-label Desvenlafaxine 50 mg/d entered a 12-week open-label stability phase. Patients with a continuing, stable response at week 20 were randomly assigned to 6-month, double-blind treatment (Desvenlafaxine 50 mg/d or placebo). Study 1 was conducted between June 2009 and March 2011 at 87 sites worldwide. Study 2: week 12 responders to open-label Desvenlafaxine 200 or 400 mg/d were randomly assigned to 6-month, double-blind treatment (Desvenlafaxine 200 mg/d, 400 mg/d, or placebo). Study 2 was conducted between June 2003 and August 2005 at 49 sites in Europe, the United States, and Taiwan. Relapse was assessed separately by study with log-rank test using protocol definitions of relapse and with 17-item Hamilton Depression Rating Scale (HDRS-17) score ≥ 16 at any time during the double-blind phase. Kaplan-Meier estimates evaluated time to relapse, censoring data at months 1, 2, and 3 and overall; treatments were compared using hazard ratios. Cox proportional hazards models assessed relapse predictors. Results: Overall relapse rates for all definitions were significantly lower for Desvenlafaxine versus placebo for both studies (all P ≤ .002). In study 1, rates were significantly lower for Desvenlafaxine versus placebo at month 2 (P = .016) and month 3 (P = .007) using the protocol definition. In study 2, relapse rates were significantly lower for Desvenlafaxine versus placebo at months 1, 2, and 3 for both definitions (P < .0001–.002). Hazard ratios were similar at months 1, 2, and 3 and overall for both studies (0.382–0.639). Conclusions: Desvenlafaxine 50 to 400 mg/d effectively prevented relapse at 6 months. Desvenlafaxine significantly prevented relapse early (month 1) versus placebo only in study 2. Trial Registration: ClinicalTrials.gov identifiers:NCT00887224 and NCT00075257
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improvements in quality of life with Desvenlafaxine 50mg d vs placebo in employed adults with major depressive disorder
Journal of Affective Disorders, 2014Co-Authors: Jean Endicott, Matthieu Boucher, Rana Fayyad, Christine J GuicopabiaAbstract:Abstract Background Diminished quality of life (QOL) is associated with major depressive disorder (MDD). Methods QOL was assessed in a post-hoc analysis of a double-blind, placebo-controlled trial. Employed adult outpatients with MDD were randomly assigned to 12 weeks of treatment with Desvenlafaxine 50 mg/d or placebo. Changes from baseline in the Short Form of the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) item scores at week 12 were analyzed using analysis of covariance with treatment, region, and baseline in the model. Correlations between change from baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D 17 ) total score and Q-LES-Q scores were computed. Results The intent-to-treat population included 427 patients. There were statistically significant improvements from baseline for Desvenlafaxine vs placebo in 10 of 16 Q-LES-Q item scores ( P values ≤0.0441). The percentage of patients with severe QOL impairment (≥2 SD below community norm) at week 12 was significantly lower for Desvenlafaxine (46%) vs placebo (62%; P =0.0024; baseline: 95% and 94%, respectively). Change in Q-LES-Q total score was highly correlated with change in HAM-D 17 score at week 12, LOCF ( P 17 total score at week 2 predicted change in Q-LES-Q total score at week 12 for the Desvenlafaxine group ( F =24.89; P Limitations This analysis excluded patients who were unemployed, had severe comorbidities, and those taking multiple, concomitant medications. Conclusion Improvement in QOL and depressive symptoms was significantly greater for employed depressed patients treated with Desvenlafaxine vs placebo.
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the effect of Desvenlafaxine 50 mg day on a subpopulation of anxious depressed patients a pooled analysis of seven randomized placebo controlled studies
Human Psychopharmacology-clinical and Experimental, 2014Co-Authors: Susan G Kornstein, Christine J Guicopabia, Rana FayyadAbstract:Background Desvenlafaxine (administered as Desvenlafaxine succinate) for anxious depression was assessed in a post hoc analysis. Methods Data were pooled from patients randomly assigned to Desvenlafaxine 50 mg/day or placebo in seven double-blind, fixed-dose studies in adults with major depressive disorder. Patients with “anxious depression” had baseline 17-item Hamilton Rating Scale for Depression, anxiety–somatization factor (HAM-D17 A/S) scores ≥7. Primary end point was change in HAM-D17 scores from baseline at week 8 (last observation carried forward), evaluated using analysis of covariance with treatment, study, and baseline value as covariates. Results A total of 1873/2706 (69%) patients were identified as “anxious depressed”. Desvenlafaxine significantly improved HAM-D17 total scores versus placebo in anxious (adjusted mean [95% CI] −1.72 [−2.35, −1.09]; p < 0.001) and nonanxious (−1.48 [−2.40, −0.57]; p = 0.002) populations, with no significant treatment-by-anxiety interaction. Response and remission rates (HAM-D17) were significantly higher with Desvenlafaxine compared with placebo in both populations. Treatment-emergent adverse events were reported by 78% and 69% (Desvenlafaxine versus placebo, respectively) of anxious depressed patients and by 77% and 68% of nonanxious patients. Conclusion Desvenlafaxine 50 mg/day significantly improved depressive symptoms compared with placebo in major depressive disorder patients with clinically relevant anxiety symptoms. Improvement in the HAM-D17 total score was similar for anxious/nonanxious groups. Copyright © 2014 John Wiley & Sons, Ltd.
Rana Fayyad - One of the best experts on this subject based on the ideXlab platform.
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the effect of Desvenlafaxine on cognitive functioning in employed outpatients with major depressive disorder a substudy of a randomized double blind placebo controlled trial
Journal of Psychopharmacology, 2016Co-Authors: Christine J Guicopabia, Sujana Reddy, Rana Fayyad, Chris Edgar, Keith WesnesAbstract:The objective of this substudy was to examine the effect of Desvenlafaxine 50 mg/day compared with placebo on cognitive function in employed outpatients with major depressive disorder. A total of 11/55 (20%) study sites in a 12-week, randomized, double-blind, placebo-controlled trial administered cognitive assessments in memory, attention, and executive functioning domains using the cognitive drug research system. Changes from baseline were subjected to analysis of covariance with baseline levels as covariates, using last observation carried forward data. A significant improvement with Desvenlafaxine 50 mg/day (n=52) compared with placebo (n=29) was observed on the quality of working memory composite measure (0.081 units (0.005, 0.156); P=0.0365) at last observation carried forward. Improvement from baseline on the speed of working memory composite was significant for Desvenlafaxine (−226.6 msec (−316.7, −136.4); P<0.0001) and for placebo (−133.3 msec (−257.2, −9.4); P=0.0354); however, the treatment effe...
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an integrated analysis of the efficacy and safety of Desvenlafaxine in the treatment of major depressive disorder
International Clinical Psychopharmacology, 2016Co-Authors: J L Carrasco, Rana Fayyad, Susan G Kornstein, Roger S Mcintyre, Rita Prieto, Maribel Salas, Joan Mackell, Matthieu BoucherAbstract:The chronic course of major depressive disorder (MDD) often impedes the ability of patients to achieve full remission. Return of full functioning is a critical goal of antidepressant pharmacotherapy as the presence of residual depressive symptoms is associated with an increased risk of relapse. Treatment guidelines recommend selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, or atypical antidepressants as first-line treatment for moderate to severe MDD. Desvenlafaxine, administered as Desvenlafaxine succinate, is an serotonin-norepinephrine reuptake inhibitor approved for the treatment of adults with MDD at the recommended dose of 50 mg/day. The aim of this integrated analysis was to assess the efficacy and safety of Desvenlafaxine 50 and 100 mg/day compared with placebo in adult outpatients with MDD. The analysis used data from nine fixed-dose, short-term, placebo-controlled studies in adult outpatients diagnosed with MDD who had depressive symptoms for at least 30 days. Data from 4279 and 4317 patients were pooled for the efficacy and safety analyses, respectively. Statistically significant improvements were observed with Desvenlafaxine 50 and 100 mg/day versus placebo for all efficacy endpoints assessed, including improvements in depressive symptoms, response and remission rates, as well as functional and cognitive outcomes. Treatment with Desvenlafaxine 50 and 100 mg/day was generally safe and well tolerated. The findings of this integrated analysis of data from a large population of patients with MDD confirmed the antidepressant efficacy of both Desvenlafaxine doses and add to previous evidence supporting the efficacy of Desvenlafaxine.
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effects of Desvenlafaxine on blood pressure in patients treated for major depressive disorder a pooled analysis
Current Medical Research and Opinion, 2015Co-Authors: Michael E Thase, Rufong J Cheng, Christine J Guicopabia, Rana Fayyad, Matthieu Boucher, Jonathan Sporn, Karen A TourianAbstract:AbstractObjective:To evaluate the effect of the serotonin-norepinephrine re-uptake inhibitor Desvenlafaxine on blood pressure and incidence of new onset hypertension in pooled short-term studies and in two longer-term, randomized withdrawal studies.Research design and methods:Data from patients randomly assigned to Desvenlafaxine 10 mg to 400 mg/day or placebo in 11 short-term (8–12 weeks), fixed-dose, double-blind, placebo-controlled studies of major depressive disorder (MDD) were pooled for analysis; two Desvenlafaxine randomized withdrawal studies (36 and 46 weeks) were analyzed separately.Clinical trial registration:www.clinicaltrials.gov, NCT00072774, NCT00073762, NCT00277823, NCT00300378, NCT00384033, NCT00798707, NCT00863798, NCT01121484, NCT00824291, NCT01432457, NCT00075257, NCT00887224.Main outcome measures:Outcomes included change from baseline in supine systolic blood pressure (SSBP) and supine diastolic blood pressure (SDBP), assessed using a mixed model repeated measures (MMRM) analysis, and...
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an analysis of relapse rates and predictors of relapse in 2 randomized placebo controlled trials of Desvenlafaxine for major depressive disorder
The Primary Care Companion To The Journal of Clinical Psychiatry, 2015Co-Authors: Roger S Mcintyre, Christine J Guicopabia, Rana Fayyad, Matthieu BoucherAbstract:Objective: To evaluate relapse rates and predictors of relapse in 2 randomized, placebo-controlled trials of Desvenlafaxine for major depressive disorder (MDD). Method: Study 1: week 8 responders to open-label Desvenlafaxine 50 mg/d entered a 12-week open-label stability phase. Patients with a continuing, stable response at week 20 were randomly assigned to 6-month, double-blind treatment (Desvenlafaxine 50 mg/d or placebo). Study 1 was conducted between June 2009 and March 2011 at 87 sites worldwide. Study 2: week 12 responders to open-label Desvenlafaxine 200 or 400 mg/d were randomly assigned to 6-month, double-blind treatment (Desvenlafaxine 200 mg/d, 400 mg/d, or placebo). Study 2 was conducted between June 2003 and August 2005 at 49 sites in Europe, the United States, and Taiwan. Relapse was assessed separately by study with log-rank test using protocol definitions of relapse and with 17-item Hamilton Depression Rating Scale (HDRS-17) score ≥ 16 at any time during the double-blind phase. Kaplan-Meier estimates evaluated time to relapse, censoring data at months 1, 2, and 3 and overall; treatments were compared using hazard ratios. Cox proportional hazards models assessed relapse predictors. Results: Overall relapse rates for all definitions were significantly lower for Desvenlafaxine versus placebo for both studies (all P ≤ .002). In study 1, rates were significantly lower for Desvenlafaxine versus placebo at month 2 (P = .016) and month 3 (P = .007) using the protocol definition. In study 2, relapse rates were significantly lower for Desvenlafaxine versus placebo at months 1, 2, and 3 for both definitions (P < .0001–.002). Hazard ratios were similar at months 1, 2, and 3 and overall for both studies (0.382–0.639). Conclusions: Desvenlafaxine 50 to 400 mg/d effectively prevented relapse at 6 months. Desvenlafaxine significantly prevented relapse early (month 1) versus placebo only in study 2. Trial Registration: ClinicalTrials.gov identifiers:NCT00887224 and NCT00075257
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the effect of Desvenlafaxine 50 mg day on a subpopulation of anxious depressed patients a pooled analysis of seven randomized placebo controlled studies
Human Psychopharmacology-clinical and Experimental, 2014Co-Authors: Susan G Kornstein, Christine J Guicopabia, Rana FayyadAbstract:Background Desvenlafaxine (administered as Desvenlafaxine succinate) for anxious depression was assessed in a post hoc analysis. Methods Data were pooled from patients randomly assigned to Desvenlafaxine 50 mg/day or placebo in seven double-blind, fixed-dose studies in adults with major depressive disorder. Patients with “anxious depression” had baseline 17-item Hamilton Rating Scale for Depression, anxiety–somatization factor (HAM-D17 A/S) scores ≥7. Primary end point was change in HAM-D17 scores from baseline at week 8 (last observation carried forward), evaluated using analysis of covariance with treatment, study, and baseline value as covariates. Results A total of 1873/2706 (69%) patients were identified as “anxious depressed”. Desvenlafaxine significantly improved HAM-D17 total scores versus placebo in anxious (adjusted mean [95% CI] −1.72 [−2.35, −1.09]; p < 0.001) and nonanxious (−1.48 [−2.40, −0.57]; p = 0.002) populations, with no significant treatment-by-anxiety interaction. Response and remission rates (HAM-D17) were significantly higher with Desvenlafaxine compared with placebo in both populations. Treatment-emergent adverse events were reported by 78% and 69% (Desvenlafaxine versus placebo, respectively) of anxious depressed patients and by 77% and 68% of nonanxious patients. Conclusion Desvenlafaxine 50 mg/day significantly improved depressive symptoms compared with placebo in major depressive disorder patients with clinically relevant anxiety symptoms. Improvement in the HAM-D17 total score was similar for anxious/nonanxious groups. Copyright © 2014 John Wiley & Sons, Ltd.
Q Jiang - One of the best experts on this subject based on the ideXlab platform.
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clinical outcomes following switch from venlafaxine er to Desvenlafaxine in nonresponders and responders
Current Medical Research and Opinion, 2011Co-Authors: Christine J Guicopabia, Q Jiang, Philip T Ninan, Michael E ThaseAbstract:AbstractObjective:This post hoc analysis examined efficacy and tolerability of open-label Desvenlafaxine in patients with major depressive disorder switched from blinded placebo, venlafaxine extended release (ER), or Desvenlafaxine.Research design and methods:Patients who completed 8 weeks of double-blind therapy with placebo (n = 176), venlafaxine ER (n = 175), or Desvenlafaxine (n = 143) enrolled in a 10-month, open-label extension study and received Desvenlafaxine 200 to 400 mg/d. Efficacy (17-item Hamilton Depression Rating Scale [HDRS17]) was assessed separately for nonresponders and responders to double-blind treatment. Tolerability during the first month of open-label Desvenlafaxine was assessed.Results:Among nonresponders (n = 134) to double-blind placebo, venlafaxine ER, and Desvenlafaxine, mean decreases in HDRS17 scores were −10.9, −7.3, and −7.7, respectively; HDRS17 response rates were 67%, 53%, and 48%, respectively. Although responders (n = 360) to double-blind placebo, venlafaxine ER, and ...
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short term efficacy and safety of Desvenlafaxine in a randomized placebo controlled study of perimenopausal and postmenopausal women with major depressive disorder
The Journal of Clinical Psychiatry, 2010Co-Authors: Susan G Kornstein, Sujana Reddy, Q Jiang, Jeff Musgnung, Christine J GuicopabiaAbstract:Background: The risk for major depressive disorder (MDD) increases during the menopausal transition. Nonetheless, no large, placebo-controlled studies have prospectively assessed the efficacy of antidepressants in perimenopausal or postmenopausal women. This randomized, double-blind, placebo-controlled trial evaluated the short-term efficacy and safety of Desvenlafaxine (administered as Desvenlafaxine succinate) in perimenopausal and postmenopausal women with DSM-IV-defined MDD. Method: 387 depressed perimenopausal and postmenopausal women aged 40 to 70 years were randomly assigned to placebo or Desvenlafaxine (100 or 200 mg/d at the discretion of the investigator) in an 8-week, flexible-dose trial conducted from September 2006 to June 2008. The primary efficacy variable was change from baseline in 17-item Hamilton Depression Rating Scale (HDRS 17 ) total score, analyzed using a mixed-effects model for repeated-measures analysis. Safety data were collected throughout the trial. Results: The reduction in adjusted HERS 17 total scores from baseline to week 8 (mean daily dose after titration, 162 to 176 mg/d) was significantly greater for Desvenlafaxine (-12.64) compared with placebo (-8.33; P< .001). Statistical separation from placebo was observed at week 1 and was sustained through week 8. Both the perimenopausal and postmenopausal subgroups achieved significant reductions in HDRS 17 total scores with Desvenlafaxine treatment (perimenopausal, P=.003 ; postmenopausal, P<.001). Response (58.6%) and remission (38.2%) rates were significantly higher for Desvenlafaxine compared with placebo (31.6% [P <.001] and 22.4% [P =.008], respectively). In all, 19/256 (7.4%) Desvenlafaxine-treated patients and 4/125 (3.2%) placebo-treated patients discontinued due to adverse events. Treatment-emergent adverse events were reported by 94/125 (75.2%) placebo-treated patients and 218/256 (85.2%) Desvenlafaxine-treated patients. Conclusions: Short-term treatment with Desvenlafaxine was effective and generally well tolerated in perimenopausal and postmenopausal women with MDD.
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Short-Term Efficacy and Safety of Desvenlafaxine in a Randomized, Placebo-Controlled Study of Perimenopausal and Postmenopausal Women With Major Depressive Disorder
The Journal of Clinical Psychiatry, 2010Co-Authors: Susan G Kornstein, Sujana Reddy, Q Jiang, Jeff Musgnung, Christine J. Guico-pabiaAbstract:Background: The risk for major depressive disorder (MDD) increases during the menopausal transition. Nonetheless, no large, placebo-controlled studies have prospectively assessed the efficacy of antidepressants in perimenopausal or postmenopausal women. This randomized, double-blind, placebo-controlled trial evaluated the short-term efficacy and safety of Desvenlafaxine (administered as Desvenlafaxine succinate) in perimenopausal and postmenopausal women with DSM-IV-defined MDD. Method: 387 depressed perimenopausal and postmenopausal women aged 40 to 70 years were randomly assigned to placebo or Desvenlafaxine (100 or 200 mg/d at the discretion of the investigator) in an 8-week, flexible-dose trial conducted from September 2006 to June 2008. The primary efficacy variable was change from baseline in 17-item Hamilton Depression Rating Scale (HDRS 17 ) total score, analyzed using a mixed-effects model for repeated-measures analysis. Safety data were collected throughout the trial. Results: The reduction in adjusted HERS 17 total scores from baseline to week 8 (mean daily dose after titration, 162 to 176 mg/d) was significantly greater for Desvenlafaxine (-12.64) compared with placebo (-8.33; P< .001). Statistical separation from placebo was observed at week 1 and was sustained through week 8. Both the perimenopausal and postmenopausal subgroups achieved significant reductions in HDRS 17 total scores with Desvenlafaxine treatment (perimenopausal, P=.003 ; postmenopausal, P
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Desvenlafaxine and escitalopram for the treatment of postmenopausal women with major depressive disorder
Menopause, 2010Co-Authors: Claudio N Soares, Cecelia P Kane, Christine J Guicopabia, Q Jiang, Anita H Clayton, Kristen Focht, Susan G Kornstein, Michael E Thase, Philip T Ninan, Lee S CohenAbstract:Objective: This study assessed the efficacy, safety, and tolerability of the serotonin-norepinephrine reuptake inhibitor Desvenlafaxine and the selective serotonin reuptake inhibitor escitalopram for major depressive disorder (MDD) in postmenopausal women. Methods: In this randomized, double-blind study, postmenopausal outpatients (aged 40-70 y) with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition MDD received flexible-dose Desvenlafaxine (100-200 mg/d) or escitalopram (10-20 mg/d) for 8 weeks. Acute-phase responders, that is, women with a 50% or greater reduction from baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D 17 ) total score, were eligible to continue the same double-blind treatment in the 6-month continuation phase. The primary efficacy outcomes were mean change from baseline in HAM-D 17 total score (acute phase), analyzed using a mixed-effects model for repeated measures, and the proportion of women who maintained response (continuation phase), analyzed using logistic regression. Results: Reductions in HAM-D 17 total score at acute-phase endpoint were similar for Desvenlafaxine- and escitalopram-treated women (—13.6 vs —14.3, respectively; P = 0.24). No significant difference was observed between groups at continuation-phase endpoint in the proportion of women who maintained response (Desvenlafaxine, 82%; escitalopram, 80%; P = 0.70). In both phases, Desvenlafaxine and escitalopram were generally safe and well tolerated. Conclusions: 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.
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assessing the efficacy of Desvenlafaxine for improving functioning and well being outcome measures in patients with major depressive disorder a pooled analysis of 9 double blind placebo controlled 8 week clinical trials
The Journal of Clinical Psychiatry, 2009Co-Authors: Claudio N Soares, Susan G Kornstein, Q Jiang, Michael E Thase, Christine J GuicopabiaAbstract:OBJECTIVE: To evaluate the effects of Desvenlafaxine therapy on functioning and well-being in major depressive disorder (MDD). METHOD: Total and individual item Sheehan Disability Scale (SDS) and 5-item World Health Organization Well-Being Index (WHO-5) scores from 8 double-blind, placebo-controlled, 8-week Desvenlafaxine clinical trials were pooled. Scores on the 17-item Hamilton Depression Rating Scale (HDRS(17)) work/activities and Montgomery-Asberg Depression Rating Scale (MADRS) lassitude items were pooled from 9 studies. Outpatients with DSM-IV MDD were randomly assigned to fixed (5 studies; 50, 100, 200, or 400 mg/d; n = 1,342) or flexible (4 studies, 100-400 mg/d; n = 463) doses of Desvenlafaxine or placebo (n = 1,108). Data from each patient's final evaluation were analyzed for the total population and for individual dose groups from the fixed-dose studies and were compared between groups using analysis of covariance. RESULTS: Compared with placebo, Desvenlafaxine therapy resulted in significantly greater improvements in SDS total score (-2.0) and individual items regarding work (-0.6), social life/leisure activities (-0.8), and family life/home responsibilities (-0.7; P < .001 for all comparisons), as well as WHO-5 total score (1.7) and individual items (good spirits [0.4], calm/relaxed [0.4], active/vigorous [0.3], fresh/rested [0.3], and interest [0.3]; P < .001 for all comparisons). Desvenlafaxine treatment resulted in significant improvements on the HDRS(17) work/activities (-0.2; P < .001) and MADRS lassitude (-0.3; P < .001) items compared with placebo. Significant differences were observed for the individual fixed-dose groups on all outcomes (P < .05); there was no evidence of a dose-response relationship. CONCLUSIONS: Desvenlafaxine therapy resulted in significant improvements in the functioning and well-being among MDD patients.
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pharmacokinetics and tolerability of single ascending doses of Desvenlafaxine administered to children and adolescents with major depressive disorder
Journal of Child and Adolescent Psychopharmacology, 2016Co-Authors: Robert L Findling, Karen A Tourian, James Groark, Sara Ramaker, Deborah Chiles, Lingfeng Yang, Alice I NicholsAbstract:Abstract Objective: To investigate the safety and pharmacokinetic profile of ascending doses of Desvenlafaxine in children and adolescents with major depressive disorder. Assessment of the effect of Desvenlafaxine on depression symptoms was exploratory. Methods: The 8-week, open-label study included an initial 3.5-day inpatient period followed by a 7.5-week outpatient period. Children (7–11 years) received a single Desvenlafaxine dose of 10, 25, 50, or 100 mg on day 1; adolescents (12–17 years) received Desvenlafaxine 25, 50, 100, or 200 mg/day. Plasma and urine samples were collected over the initial 72-hour inpatient period. Evaluations included treatment-emergent adverse events (TEAEs), physical examinations (including Tanner Staging), vital signs, laboratory assessments, 12-lead electrocardiogram, Columbia-Suicide Severity Rating Scale, and the Children's Depression Rating Scale-Revised (CDRS-R). Results: In all, 29 children and 30 adolescents took at least one dose of Desvenlafaxine and were included...
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an open label single dose parallel group study of the effects of chronic hepatic impairment on the safety and pharmacokinetics of Desvenlafaxine
Clinical Therapeutics, 2013Co-Authors: Susan Bairdbellaire, Jessica A Behrle, Vernon D Parker, Jeffrey Paul, Alain Patat, Alice I NicholsAbstract:Abstract Background Many antidepressants are extensively metabolized in the liver, requiring dose adjustments in individuals with hepatic impairment. Clinical studies indicate that the serotonin-norepinephrine reuptake inhibitor Desvenlafaxine is metabolized primarily via glucuronidation, and ∼45% is eliminated unchanged in urine. Objective The objectives of this study were to assess the pharmacokinetic profile, safety, and tolerability of Desvenlafaxine in adults with chronic Child-Pugh class A, B, and C hepatic impairment. Methods Subjects (aged 18–65 years) with mild (Child-Pugh class A, n = 8), moderate (Child-Pugh class B, n = 8), and severe (Child-Pugh class C, n = 8) hepatic impairment and 12 healthy matched subjects received a single 100-mg oral dose of Desvenlafaxine. Disposition of (R)-, (S)-, and (R+S)-enantiomers of Desvenlafaxine were examined in plasma and urine. Geometric least squares (GLS) mean ratios and 90% CIs for AUC, AUC 0–τ , C max , and Cl/F were calculated; comparisons were made by using a 1-factor ANOVA. Safety was evaluated according to adverse events, physical examination, vital signs, and laboratory assessments. Results Healthy participants had a mean age of 51 years (range, 36–62 years) and weight of 79.1 kg (range, 52.5–105.0 kg); hepatically impaired participants had a mean age of 52 years (range, 31–65 years) and weight of 80.9 kg (range, 50.2–119.5 kg). In both groups, 67% of participants were male. No statistically significant differences (≥50%) in the disposition of Desvenlafaxine were detected between hepatically impaired patients and healthy subjects based on GLS mean ratios for C max , AUC 0–τ , AUC, or Cl/F ( P > 0.05 for each comparison). Median T max was similar for all groups (range, 6–9 hours). A nonsignificant increase was observed for Desvenlafaxine exposure in patients with moderate or severe hepatic impairment (GLS mean ratios [90% CIs] for AUC, 31% [93.2–184], 35% [96.5–190], respectively). The most common adverse events were nausea (n = 2, healthy subjects; n = 3, hepatically impaired subjects) and vomiting (n = 1, healthy subjects; n = 2, hepatically impaired subjects). Conclusions A single 100-mg dose of Desvenlafaxine was well tolerated in healthy subjects and hepatically impaired patients. A mild increase in exposure was observed for moderate and severe hepatically impaired subjects (Child-Pugh class B and C).
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effects of age and sex on the pharmacokinetics safety and tolerabilityof oral Desvenlafaxine in healthy adults
Journal of Bioequivalence & Bioavailability, 2013Co-Authors: Alice I Nichols, Jessica A Behrle, Lyette S Richards, Joel A Posener, Richard J Fruncillo, Jeffrey PaulAbstract:Background: Desvenlafaxine (administered as Desvenlafaxine succinate) is a serotonin-norepinephrine reuptake inhibitor approved for treatment of major depressive disorder. Because it is primarily eliminated unchanged by renal excretion, it is important to characterize the effect of patient factors, such as age and sex that may influence renal clearance. Methods: The pharmacokinetics, safety, and tolerability of a single oral dose of Desvenlafaxine were assessed in healthy adults stratified by age (young, 18-45 years; elderly, 65-75; very old, >75) and sex in an open-label, inpatient trial. Results: Desvenlafaxine was generally well tolerated and was slowly absorbed in all age groups. Mean values for peak plasma concentration (C max ) for women exceeded those of men (P 75 years.
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An Evaluation of the Potential of Cytochrome P450 3A4-Mediated Drug-Drug Interactions with Desvenlafaxine Use
Journal of Bioequivalence & Bioavailability, 2013Co-Authors: Alice I Nichols, Jessica A Behrle, Joel A Posener, Jeffrey Paul, Yali Liang, Kyle Matschke, Alain Patat, Shannon Lubaczewski, Gabriel Braley, Tanya RameyAbstract:A series of 3 open-label, 2-period, sequential studies were conducted to assess the impact of Desvenlafaxine on cytochrome P450 3A4 (CYP3A4) enzyme-mediated metabolism, and the effect of CYP3A4 inhibition on Desvenlafaxine metabolism. Study 1 evaluated a single dose of Desvenlafaxine 400 mg administered alone or with a CYP3A4 inhibitor (ketoconazole [400 mg/d for 8 days]). Studies 2 and 3 evaluated a single dose of CYP3A4 substrate (midazolam [4 mg]) administered alone or with multiple doses of Desvenlafaxine 400 mg and 50 mg (the recommended therapeutic dose), respectively, to assess the potential inhibitory effect of Desvenlafaxine. In study 1, Desvenlafaxine peak plasma concentration (Cmax) and area under the plasma concentration-versus-time curve (AUC) geometric least-squares mean ratios (Desvenlafaxine and ketoconazole vs. Desvenlafaxine alone) were 108% (90% confidence interval [CI], 100% to 117%) and 143% (90% CI, 138% to 149%), respectively. Total oral clearance decreased by 29% with ketoconazole coadministration. In studies 2 and 3, Cmax and AUC geometric least-squares mean ratios (midazolam and Desvenlafaxine vs. midazolam alone) were 84% (90% CI, 72% to 97%) and 69% (90% CI, 61% to 78%), respectively, for the Desvenlafaxine 400-mg dose, and 86% (90% CI, 79% to 94%) and 71% (90% CI, 65% to 78%), respectively, for the Desvenlafaxine 50-mg dose. No serious adverse events or safety-related discontinuations occurred. Desvenlafaxine is minimally metabolized by CYP3A4 and does not appear to inhibit CYP3A4.
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An Assessment of the Pharmacokinetics and Tolerability of Single-AscendingDoses of Desvenlafaxine Administered to Healthy Chinese Subjects
Journal of Bioequivalence & Bioavailability, 2013Co-Authors: Lingling Guan, Huafang Li, Zhangjing Chen, Glen Frick, Alice I NicholsAbstract:Desvenlafaxine (administered as Desvenlafaxine succinate) exhibited linear pharmacokinetics after singledose administration in a US population. The current study assessed the pharmacokinetics and tolerability of singleascending doses of Desvenlafaxine in Chinese subjects. Healthy adult subjects of Chinese descent living in China were randomly assigned to receive either a single dose of Desvenlafaxine 50, 100, 200 mg, or placebo in this sponsor-unblinded, inpatient, ascending-dose study. Desvenlafaxine concentrations in urine and plasma were measured using a validated liquid chromatography/tandem mass spectrometry method. Peak plasma concentration (Cmax) and time to Cmax (tmax) were determined directly from observed data, and area under the plasma concentrationversus- time curve (AUC) was computed. Dose proportionality for Cmax and AUC was examined using a power model. Tolerability was assessed through adverse event (AE) reporting. Thirty-six subjects were enrolled. The Cmax of Desvenlafaxine increased 138% between the 50 mg (109 ng/mL) and 100 mg (259 ng/mL) doses. The Cmax for subjects receiving Desvenlafaxine 200 mg was 654 ng/mL, a 153% increase compared with the 100 mg dose. The AUC of Desvenlafaxine increased 127% from the 50 mg dose (2,520 ng•hr/mL) to the 100 mg dose (5,720 ng•hr/ mL), and 126% between the 100 mg and 200 mg (12,900 ng•hr/mL) doses. The power model analysis indicated dose proportionality for AUC, but not for Cmax. No serious AEs were reported. Desvenlafaxine was generally well tolerated in healthy Chinese subjects, and its exposure (AUC) was dose-proportional. Results from this study and studies in US, European, and Japanese populations indicate that the pharmacokinetics of Desvenlafaxine were comparable between these ethnic groups.