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David J Carpenter - One of the best experts on this subject based on the ideXlab platform.
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meta analysis of efficacy and treatment emergent suicidality in adults by psychiatric indication and age subgroup following initiation of Paroxetine therapy a complete set of randomized placebo controlled trials
2011Co-Authors: David J Carpenter, Regan Fong, John E Kraus, John T Davies, Christine Moore, Michael E ThaseAbstract:OBJECTIVE: This meta-analysis of placebo-controlled Paroxetine trials examines suicidality incidence in adults, focusing on disorder and age as potential risk factors. The findings are put in context with an efficacy meta-analysis of the same trial datasets. DATA SOURCES: GlaxoSmithKline Paroxetine clinical trial database(s). STUDY SELECTION: All double-blind, randomized, placebo-controlled, parallel-group studies of Paroxetine therapy in adults enrolling at least 30 patients total were included in the analysis. The dataset comprised 14,911 patients from 61 trials. DATA EXTRACTION: Possible cases of suicidality were identified and blindly categorized by an expert panel, using methodology previously used by the US Food and Drug Administration. Incidences of suicidal behavior (preparatory act, suicide attempt, or completed suicide) and any suicidality (suicidal behavior or ideation) were compared between Paroxetine and placebo. Efficacy assessments were based on standard depression rating scales (eg, Hamilton Depression Rating Scale or Montgomery-Asberg Depression Rating Scale) and Clinical Global Impressions Improvement scale (CGI-I) scores. RESULTS: In the primary dataset, ie, all disorders combined, there were no significant differences between Paroxetine and placebo for overall suicidality (suicidal behavior or ideation: n/n = 83/8,958 [0.93%] vs n/n = 65/5,953 [1.09%], respectively; OR = 0.9 [95% CI, 0.7-1.3]; P = .649) or for suicidal behavior specifically (n/n = 50/8,958 [0.56%] vs n/n = 40/5,953 [0.67%], respectively; OR = 1.2 [95% CI, 0.8-1.9]; P = .483). However, in patients with major depressive disorder (MDD), a greater incidence of suicidal behavior occurred in Paroxetine-treated patients than in placebo-treated patients (n/n = 11/3,455 [0.32%] vs n/n = 1/1,978 [0.05%], respectively; OR = 6.7 [95% CI, 1.1-149.4]; P = .058). Across all indications, a higher incidence of suicidal behavior occurred in Paroxetine-treated versus placebo-treated adults aged 18 to 24 years (n/n = 17/776 [2.19%] vs n/n = 5/542 [0.92%], respectively; OR = 2.4 [95% CI, 0.9-7.3]). In older age groups, no increase in suicidality was observed. Efficacy was demonstrated in all disorders evaluated, including MDD. CONCLUSIONS: Across all disorders, overall suicidality incidence was similar between Paroxetine and placebo. However, a higher frequency of suicidal behavior occurred with Paroxetine in MDD, which was largely explained by the higher incidence in young adults. These data support the efficacy of Paroxetine therapy; however, they also highlight the need for careful monitoring of suicidality during antidepressant therapy, particularly in younger adults.
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estimates of serotonin and norepinephrine transporter inhibition in depressed patients treated with Paroxetine or venlafaxine
2008Co-Authors: Michael J Owens, David J Carpenter, Michael E Thase, Stan Krulewicz, Jeffrey S Simon, David V Sheehan, Susan J Plott, Charles B NemeroffAbstract:Paroxetine and venlafaxine are potent serotonin transporter (SERT) antagonists and weaker norepinephrine transporter (NET) antagonists. However, the relative magnitude of effect at each of these sites during treatment is unknown. Using a novel blood assay that estimates CNS transporter occupancy we estimated the relative SERT and NET occupancy of Paroxetine and venlafaxine in human subjects to assess the relative magnitude of SERT and NET inhibition. Outpatient subjects (N=86) meeting criteria for major depression were enrolled in a multicenter, 8 week, randomized, double-blind, parallel group, antidepressant treatment study. Subjects were treated by forced-titration of Paroxetine CR (12.5–75 mg/day) or venlafaxine XR (75–375 mg/day) over 8 weeks. Blood samples were collected weekly to estimate transporter inhibition. Both medications produced dose-dependent inhibition of the SERT and NET. Maximal SERT inhibition at week 8 for Paroxetine and venlafaxine was 90% (SD 7) and 85% (SD 10), respectively. Maximal NET inhibition for Paroxetine and venlafaxine at week 8 was 36% (SD 19) and 60% (SD 13), respectively. The adjusted mean change from baseline (mean 28.6) at week 8 LOCF in MADRS total score was −16.7 (SE 8.59) and −17.3 (SE 8.99) for the Paroxetine and venlafaxine-treated patients, respectively. The magnitudes of the antidepressant effects were not significantly different from each other (95%CI −3.42, 4.54, p=0.784). The results clearly demonstrate that Paroxetine and venlafaxine are potent SERT antagonists and less potent NET antagonists in vivo. NET antagonism has been posited to contribute to the antidepressant effects of these compounds. The clinical significance of the magnitude of NET antagonism by both medications remains unclear at present.
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Paroxetine treatment in children and adolescents with obsessive compulsive disorder a randomized multicenter double blind placebo controlled trial
2004Co-Authors: David J Carpenter, Daniel A Geller, Karen Dineen Wagner, Graham J Emslie, Tanya K Murphy, Erica Wetherhold, Phil PereraAbstract:ABSTRACT Objective: To assess the efficacy and safety of Paroxetine for the treatment of pediatric obsessive-compulsive disorder. Method: Children (7–11 years of age) and adolescents (12–17 years of age) meeting DSM-IV criteria for obsessive-compulsive disorder were randomized to Paroxetine (10–50 mg/day) or placebo for 10 weeks. The primary efficacy measure was change from baseline in the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) total score at week 10 last observation carried forward end point. Safety was assessed primarily through adverse event monitoring. Results: A total of 207 patients were randomized to treatment. Of these, 203 were included in the intention-to-treat population. Adjusted mean changes from baseline at week 10 observation carried forward end point in CY-BOCS total score for patients receiving Paroxetine and placebo were −8.78 (SE = 0.82) and −5.34 points (SE = 0.77), respectively. The adjusted mean difference, −3.45 in favor of Paroxetine, was statistically significant (95% confidence interval=−5.60 to −1.29, p = .002). Adverse events were generally mild to moderate in intensity. A total of 10.2% (10/98) of patients in the Paroxetine group and 2.9% (3 of 105) in the placebo group discontinued treatment because of adverse events. Conclusions: Paroxetine is an effective and generally well-tolerated treatment for obsessive-compulsive disorder in children and adolescents.
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a multicenter randomized double blind placebo controlled trial of Paroxetine in children and adolescents with social anxiety disorder
2004Co-Authors: Karen Dineen Wagner, David J Carpenter, Erica Wetherhold, Ray M F Berard, Murray B Stein, Phillip Perera, Michelle Gee, Katherine Davy, Andrea MachinAbstract:Background Social anxiety disorder is a debilitating, highly prevalent disorder in children and adolescents. If left untreated, it can interfere with emotional, social, and school functioning. Objective To evaluate the efficacy and tolerability of Paroxetine in children and adolescents with social anxiety disorder. Design and Setting Multicenter, 16-week, randomized, double-blind, placebo-controlled, flexible-dose, parallel-group, outpatient study. Patients A total of 322 children (8-11 years of age) and adolescents (12-17 years of age) with social anxiety disorder as their predominant psychiatric illness. Intervention Eligible patients were randomized (1:1) to receive Paroxetine (10-50 mg/d) or placebo. Results Four hundred twenty-five patients were screened, and 322 were randomized to treatment. Of these, 319 were included in the intention-to-treat population (Paroxetine, n = 163; placebo, n = 156). At the week 16 last observation carried forward end point, the odds of responding (Clinical Global Impression-Improvement score of 1 or 2) were statistically significantly greater for Paroxetine (77.6% response [125/161]) than for placebo (38.3% response [59/154]) (adjusted odds ratio, 7.02; 95% confidence interval, 4.07 to 12.11; P Conclusion Paroxetine is an effective, generally well-tolerated treatment for pediatric social anxiety disorder.
Michael J Detke - One of the best experts on this subject based on the ideXlab platform.
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sexual functioning assessed in 4 double blind placebo and Paroxetine controlled trials of duloxetine for major depressive disorder
2005Co-Authors: Pedro L Delgado, Stephen K Brannan, Craig H Mallinckrodt, Pierre V Tran, Robert K Mcnamara, Fujun Wang, John G Watkin, Michael J DetkeAbstract:OBJECTIVE The onset or worsening of sexual dysfunction is a common treatment-emergent side effect of antidepressant medications. Post hoc analyses of pooled data from placebo-controlled studies were utilized to assess sexual functioning in patients receiving duloxetine or Paroxetine. METHOD Acute-phase data were obtained from four 8-week, double-blind, placebo- and Paroxetine-controlled trials of similar design in which patients meeting DSM-IV criteria for major depressive disorder were randomly assigned to receive placebo (N = 371), duloxetine (40-120 mg/day; N = 736), or Paroxetine (20 mg/day; N = 359). Pooling of data from these studies was anticipated during study design. This represented all available data from duloxetine studies in which the Arizona Sexual Experience Scale (ASEX) was administered both at baseline and endpoint. Long-term data were available from extension phases in 2 of these trials in which acute treatment responders received placebo (N = 129), duloxetine (80-120 mg/day; N = 297), or Paroxetine (20 mg/day; N = 140) for an additional 26 weeks. Data were collected between March 2000 and July 2002. RESULTS The incidence of acute treatment-emergent sexual dysfunction was significantly lower among duloxetine-treated patients compared with those receiving Paroxetine (p = .015), although both rates were significantly higher than placebo (p = .007 and p < .001 for duloxetine and Paroxetine, respectively). Treatment group differences in the incidence of treatment-emergent dysfunction did not vary significantly by gender. In female patients, acute treatment-emergent sexual dysfunction was significantly lower in the duloxetine treatment group compared with the Paroxetine treatment group (p = .032), with both rates being significantly higher than placebo (p = .049 and p < .001 for duloxetine and Paroxetine, respectively). In the somewhat smaller group of male patients, acute treatment-emergent dysfunction did not differ significantly between duloxetine and placebo treatment groups, but the incidence was significantly higher in Paroxetine-treated male patients compared with male placebo patients (p = .012). The long-term incidence of treatment-emergent dysfunction did not differ significantly between duloxetine-, Paroxetine-, and placebo-treated patients. CONCLUSION In this analysis of pooled data, patients receiving duloxetine (40-120 mg/day) or Paroxetine (20 mg/day) had a significantly higher incidence of acute treatment-emergent sexual dysfunction when compared with placebo patients. However, the incidence of acute treatment-emergent dysfunction for duloxetine was significantly lower than that observed for Paroxetine.
Rocco Zaninelli - One of the best experts on this subject based on the ideXlab platform.
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efficacy and safety of Paroxetine treatment for chronic ptsd a fixed dose placebo controlled study
2001Co-Authors: Randall D Marshall, Katherine L Beebe, Mary Oldham, Rocco ZaninelliAbstract:Objective This study evaluated the efficacy and safety of Paroxetine for the treatment of patients with chronic posttraumatic stress disorder (PTSD). Method Outpatients with chronic PTSD according to DSM-IV criteria and a score of 50 or more on the Clinician-Administered PTSD Scale, part 2, were randomly assigned to take placebo (N=186), 20 mg/day of Paroxetine (N=183), or 40 mg/day of Paroxetine (N=182) for 12 weeks. Efficacy was assessed by examining the change in total score from baseline to endpoint on the Clinician-Administered PTSD Scale, part 2, and rates of response ("very much improved" or "much improved") for global improvement on the Clinical Global Impression scale. Results Paroxetine-treated patients in both dose groups demonstrated significantly greater improvement on primary outcome measures compared to placebo-treated patients in the intent-to-treat analysis. Moreover, Paroxetine treatment resulted in statistically significant improvement compared to placebo on all three PTSD symptom clusters (reexperiencing, avoidance/numbing, and hyperarousal), social and occupational impairment, and comorbid depression. Paroxetine was effective for both men and women. Treatment response did not vary by trauma type, time since trauma, or severity of baseline PTSD or depressive symptoms. Both doses were well tolerated. Conclusions Doses of 20 and 40 mg/day of Paroxetine are effective and well tolerated in the treatment of adults with chronic PTSD.
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Paroxetine in the treatment of chronic posttraumatic stress disorder results of a placebo controlled flexible dosage trial
2001Co-Authors: Phebe Tucker, Rocco Zaninelli, Rachel Yehuda, Lee Ruggiero, Kerry E Dillingham, Cornelius D PittsAbstract:BACKGROUND The objective of this double-blind, placebo-controlled study was to investigate the efficacy and safety of Paroxetine in outpatients with posttraumatic stress disorder (PTSD). METHOD Male and female outpatients 18 years and older who met DSM-IV criteria for PTSD and had baseline scores of 50 or greater on the Clinician Administered PTSD Scale (CAPS-2) were randomly assigned to treatment with Paroxetine (20-50 mg/day) or placebo for 12 weeks. The primary efficacy variables were the change from baseline to the 12-week endpoint in the CAPS-2 total score and the proportion of responders on the Clinical Global Impressions-Global Improvement scale (CGI-1). Additional key outcome measures were the change from baseline in the reexperiencing, avoidance/ numbing, and hyperarousal scores of the CAPS-2 and in the total scores of the Treatment Outcome PTSD Scale and the patient-rated Davidson Trauma Scale and Sheehan Disability Scale (SDS). Depressive symptoms were assessed with the Montgomery-Asberg Depression Rating Scale. The proportion of patients achieving response and remission was also determined. RESULTS 307 patients constituted the intent-to-treat population. At week 12, compared with the placebo group (N = 156), the Paroxetine group (N = 151) showed significantly greater reduction of PTSD symptoms on both of the primary and all of the secondary outcome measures. Significantly greater improvement on the CAPS-2 total score was observed for Paroxetine compared with placebo from week 4 (p < .05), and significantly greater proportions of Paroxetine-treated patients achieved response (p < .001) and remission (p = .008) by week 12. The improvement in PTSD symptoms was similar in male and female patients. Functional improvement at the study endpoint was significantly greater (p < .05) in the Paroxetine group in all 3 domains of the SDS (work, social life, family life). Treatment with Paroxetine was well tolerated, with the frequency and type of adverse events recorded for the Paroxetine group corresponding to the known safety profile of this medication. CONCLUSION Paroxetine in doses of 20 to 50 mg once daily is effective as a treatment for chronic PTSD. Improvement is obtained for all 3 symptom clusters (reexperiencing, avoidance/numbing, hyperarousal) and is associated with significant reduction in disability after 12 weeks of treatment.
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Paroxetine in the treatment of generalized anxiety disorder results of a placebo controlled flexible dosage trial
2001Co-Authors: Mark H Pollack, Rocco Zaninelli, Kevin M Bellew, Andrew W Goddard, James P Mccafferty, Daniel B Burnham, Malini K IyengarAbstract:BACKGROUND: The objective of this randomized, double-blind, placebo-controlled study was to investigate the efficacy and safety of Paroxetine in outpatients with generalized anxiety disorder (GAD). METHOD: Male and female outpatients 18 years and older who met DSM-IV criteria for GAD and had baseline scores of at least 20 on the Hamilton Rating Scale for Anxiety (HAM-A) were randomly assigned to treatment with Paroxetine (20-50 mg/day) or placebo for 8 weeks. The primary efficacy variable was the mean change from baseline in the total score of the HAM-A. Additional key efficacy variables were the change from baseline in the scores of the HAM-A items anxious mood and tension, the anxiety subscale of the Hospital Anxiety and Depression Scale, and the Sheehan Disability Scale (SDS). The proportions of patients fulfilling response and remission criteria at week 8 were also determined. RESULTS: The intent-to-treat population included 324 patients. At week 8, compared with the placebo group (N = 163), the Paroxetine group (N = 161) had a significantly greater reduction of GAD symptoms on all of the above-mentioned efficacy variables. On the HAM-A anxious mood item, which encompasses the cardinal symptoms of GAD, significantly greater efficacy was observed from week 1 and on the SDS significantly greater improvement was documented in the domain "social life" as early as week 4 for Paroxetine compared with placebo. In both the last-observation-carried-forward and completer data sets, significantly greater proportions of Paroxetine-treated patients achieved response or remission by week 8. Treatment with Paroxetine was well tolerated, and the number and type of adverse events recorded in the Paroxetine group correspond to the known safety profile of this medication. CONCLUSION: Paroxetine in doses of 20 to 50 mg once daily is effective in the treatment of patients with GAD. Improvement of core symptoms of GAD occurs early and is associated with significant reduction in disability after only 8 weeks of treatment.
Karen Dineen Wagner - One of the best experts on this subject based on the ideXlab platform.
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Paroxetine treatment in children and adolescents with obsessive compulsive disorder a randomized multicenter double blind placebo controlled trial
2004Co-Authors: David J Carpenter, Daniel A Geller, Karen Dineen Wagner, Graham J Emslie, Tanya K Murphy, Erica Wetherhold, Phil PereraAbstract:ABSTRACT Objective: To assess the efficacy and safety of Paroxetine for the treatment of pediatric obsessive-compulsive disorder. Method: Children (7–11 years of age) and adolescents (12–17 years of age) meeting DSM-IV criteria for obsessive-compulsive disorder were randomized to Paroxetine (10–50 mg/day) or placebo for 10 weeks. The primary efficacy measure was change from baseline in the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) total score at week 10 last observation carried forward end point. Safety was assessed primarily through adverse event monitoring. Results: A total of 207 patients were randomized to treatment. Of these, 203 were included in the intention-to-treat population. Adjusted mean changes from baseline at week 10 observation carried forward end point in CY-BOCS total score for patients receiving Paroxetine and placebo were −8.78 (SE = 0.82) and −5.34 points (SE = 0.77), respectively. The adjusted mean difference, −3.45 in favor of Paroxetine, was statistically significant (95% confidence interval=−5.60 to −1.29, p = .002). Adverse events were generally mild to moderate in intensity. A total of 10.2% (10/98) of patients in the Paroxetine group and 2.9% (3 of 105) in the placebo group discontinued treatment because of adverse events. Conclusions: Paroxetine is an effective and generally well-tolerated treatment for obsessive-compulsive disorder in children and adolescents.
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a multicenter randomized double blind placebo controlled trial of Paroxetine in children and adolescents with social anxiety disorder
2004Co-Authors: Karen Dineen Wagner, David J Carpenter, Erica Wetherhold, Ray M F Berard, Murray B Stein, Phillip Perera, Michelle Gee, Katherine Davy, Andrea MachinAbstract:Background Social anxiety disorder is a debilitating, highly prevalent disorder in children and adolescents. If left untreated, it can interfere with emotional, social, and school functioning. Objective To evaluate the efficacy and tolerability of Paroxetine in children and adolescents with social anxiety disorder. Design and Setting Multicenter, 16-week, randomized, double-blind, placebo-controlled, flexible-dose, parallel-group, outpatient study. Patients A total of 322 children (8-11 years of age) and adolescents (12-17 years of age) with social anxiety disorder as their predominant psychiatric illness. Intervention Eligible patients were randomized (1:1) to receive Paroxetine (10-50 mg/d) or placebo. Results Four hundred twenty-five patients were screened, and 322 were randomized to treatment. Of these, 319 were included in the intention-to-treat population (Paroxetine, n = 163; placebo, n = 156). At the week 16 last observation carried forward end point, the odds of responding (Clinical Global Impression-Improvement score of 1 or 2) were statistically significantly greater for Paroxetine (77.6% response [125/161]) than for placebo (38.3% response [59/154]) (adjusted odds ratio, 7.02; 95% confidence interval, 4.07 to 12.11; P Conclusion Paroxetine is an effective, generally well-tolerated treatment for pediatric social anxiety disorder.
Andrea Machin - One of the best experts on this subject based on the ideXlab platform.
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a multicenter randomized double blind placebo controlled trial of Paroxetine in children and adolescents with social anxiety disorder
2004Co-Authors: Karen Dineen Wagner, David J Carpenter, Erica Wetherhold, Ray M F Berard, Murray B Stein, Phillip Perera, Michelle Gee, Katherine Davy, Andrea MachinAbstract:Background Social anxiety disorder is a debilitating, highly prevalent disorder in children and adolescents. If left untreated, it can interfere with emotional, social, and school functioning. Objective To evaluate the efficacy and tolerability of Paroxetine in children and adolescents with social anxiety disorder. Design and Setting Multicenter, 16-week, randomized, double-blind, placebo-controlled, flexible-dose, parallel-group, outpatient study. Patients A total of 322 children (8-11 years of age) and adolescents (12-17 years of age) with social anxiety disorder as their predominant psychiatric illness. Intervention Eligible patients were randomized (1:1) to receive Paroxetine (10-50 mg/d) or placebo. Results Four hundred twenty-five patients were screened, and 322 were randomized to treatment. Of these, 319 were included in the intention-to-treat population (Paroxetine, n = 163; placebo, n = 156). At the week 16 last observation carried forward end point, the odds of responding (Clinical Global Impression-Improvement score of 1 or 2) were statistically significantly greater for Paroxetine (77.6% response [125/161]) than for placebo (38.3% response [59/154]) (adjusted odds ratio, 7.02; 95% confidence interval, 4.07 to 12.11; P Conclusion Paroxetine is an effective, generally well-tolerated treatment for pediatric social anxiety disorder.
