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Hans Eriksson - One of the best experts on this subject based on the ideXlab platform.
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pooled analysis of adjunct extended release Quetiapine fumarate in patients with major depressive disorder according to ongoing ssri or snri treatment
International Clinical Psychopharmacology, 2014Co-Authors: Michael Bauer, Nizar Elkhalili, Johan Szamosi, Willie Earley, Koen Demyttenaere, Michael E Thase, George I Papakostas, Hans ErikssonAbstract:This pooled analysis evaluated the efficacy of extended-release Quetiapine fumarate (Quetiapine XR) adjunct to selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) in patients with major depressive disorder (MDD). Pooled data were analyzed from two 6-week, double-blind, randomized, placebo-controlled trials of adjunct Quetiapine XR (150 and 300 mg/day) in patients with MDD and inadequate response to initial antidepressant monotherapy. This post-hoc analysis included evaluation of change from randomization at week 6 in Montgomery Asberg Depression Rating Scale (MADRS) total scores (primary endpoint), and week 6 MADRS response and remission rates for Quetiapine XR as an adjunct to ongoing SSRI or SNRI. In total, 189, 178, and 202 patients received Quetiapine XR 150 mg/day+SSRI, 300 mg/day+SSRI, and placebo+SSRI, respectively, whereas 82, 90, and 76 patients, respectively, received Quetiapine XR 150 mg/day+SNRI, 300 mg/day+SNRI, and placebo+SNRI. At week 6, Quetiapine XR 150 mg/day+SSRI and 300 mg/day+SSRI reduced the MADRS total score from randomization versus placebo+SSRI [least squares mean (LSM) change, -14.70 (P<0.05) -14.72 (P<0.05) vs. -12.59, respectively]. Quetiapine XR 150 mg/day+SNRI (LSM change, -14.68, P<0.01) and 300 mg/day+SNRI (LSM change, -14.99, P<0.01) also reduced the MADRS total score from randomization at week 6 versus placebo+SNRI (-10.77). In conclusion, in patients with MDD and inadequate response to ongoing antidepressant, adjunct Quetiapine XR (150 and 300 mg/day) was effective in both SSRI and SNRI subgroups.
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evaluation of the effects of extended release Quetiapine fumarate monotherapy on sleep disturbance in patients with major depressive disorder a pooled analysis of four randomized acute studies
The International Journal of Neuropsychopharmacology, 2013Co-Authors: Madhukar H. Trivedi, Johan Szamosi, Willie Earley, Borwin Bandelow, Koen Demyttenaere, George I Papakosts, Hans ErikssonAbstract:Effects of once-daily extended-release Quetiapine fumarate (Quetiapine XR) monotherapy on sleep quality and disturbance in patients with major depressive disorder (MDD) were evaluated. Pooled data from four 6- or 8-wk placebo-controlled Quetiapine XR (50-300 mg/d) monotherapy studies (D1448C00001; D1448C00002; D1448C00003; D1448C00004) were analysed. Primary efficacy end-point was change from randomization in Montgomery Asberg Depression Rating Scale (MADRS) score. Post hoc analyses of secondary end-points were conducted for change from randomization in: MADRS item 4 (reduced sleep); Hamilton Rating Scale for Depression (HAMD) items 4 (insomnia-early), 5 (insomnia-middle), 6 (insomnia-late) and sleep disturbance factor (items 4 + 5+6) scores; Pittsburgh Sleep Quality Index (PSQI) global scores. MADRS total score change was also evaluated in patients experiencing high and low baseline sleep disturbance (HAMD sleep disturbance factor scores ⩾4 and < 4, respectively). In total, 1808 patients were randomized to Quetiapine XR or placebo across four studies. At last assessment, Quetiapine XR reduced MADRS item 4, HAMD items 4, 5 and 6, HAMD sleep disturbance factor score and PSQI global scores from baseline vs. placebo (p < 0.001). For those experiencing high sleep disturbance (n = 865, Quetiapine XR; n = 514, placebo), Quetiapine XR improved MADRS total score vs. placebo at all visits (p < 0.001). For those with low sleep disturbance (n = 252, Quetiapine XR; n = 121, placebo), Quetiapine XR improved MADRS total score vs. placebo at weeks 2 (p < 0.001), 4 and 6 (both p < 0.05). In conclusion, Quetiapine XR (50-300 mg/d) monotherapy improved symptoms of sleep disturbance vs. placebo in patients with MDD, including those with either high or low baseline sleep disturbance levels.
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efficacy and tolerability of extended release Quetiapine fumarate Quetiapine xr monotherapy in major depressive disorder a placebo controlled randomized study
Journal of Affective Disorders, 2011Co-Authors: Brian Bortnick, Nizar Elkhalili, Catherine Datto, Willie Earley, Michael Banov, David E Adson, Shane Raines, Hans ErikssonAbstract:Background Evaluate the efficacy and tolerability of extended release Quetiapine fumarate (Quetiapine XR) once-daily monotherapy for patients with major depressive disorder (MDD). Methods In this 10-week, (8-week active treatment phase and 2-week drug-discontinuation/tapering phase), multicenter, parallel-group, placebo-controlled, double-blind, randomized, Phase III study (D1448C00003: Opal), patients initially received Quetiapine XR 150 mg/day or placebo. At Week 2, inadequate responders (< 20% reduction in MADRS total score) were up-titrated to 300 mg/day Quetiapine XR or matching placebo for the final 6 weeks. Primary endpoint: change from randomization to Week 8 in MADRS total score. Secondary endpoints included: MADRS response (≥ 50% reduction in total score from randomization) and changes from randomization to Week 8 in HAM-D and CGI-S. Results 310 patients were randomized. At Week 8, Quetiapine XR significantly reduced mean MADRS total score versus placebo (−16.49 vs −13.10, respectively; p 10% any group during the randomized phase) for Quetiapine XR and placebo, respectively were dry mouth (32.9% and 6.5%), sedation (21.7% and 1.9%), somnolence (20.4% and 5.2%), and headache (10.5% and 10.3%). Limitations The study was not designed to compare Quetiapine XR 150 mg/day and 300 mg/day; it was intended to reflect dose titration that might occur in clinical practice. Conclusions Quetiapine XR monotherapy is effective in patients with MDD, with symptom improvement seen as early as Week 1, and tolerability results consistent with the known profile of Quetiapine.
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a pooled analysis of two randomised placebo controlled studies of extended release Quetiapine fumarate adjunctive to antidepressant therapy in patients with major depressive disorder
Journal of Affective Disorders, 2010Co-Authors: Michael Bauer, Nizar Elkhalili, Catherine Datto, Johan Szamosi, Hans ErikssonAbstract:Abstract Background Two positive studies evaluated adjunctive extended release Quetiapine fumarate (Quetiapine XR) in patients with major depressive disorder (MDD) showing inadequate response to antidepressant treatment. This preplanned, pooled analysis provides an opportunity for subgroup analyses investigating the influence of demographic and disease-related factors on observed responses. Additional post hoc analyses examined the efficacy of Quetiapine XR against specific depressive symptoms including sleep. Methods Data were analysed from two 6-week, multicentre, double-blind, randomised, placebo-controlled studies, prospectively designed to be pooled. Patients received once-daily Quetiapine XR 150 mg/day (n = 309), 300 mg/day (n = 307) or placebo (n = 303) adjunctive to ongoing antidepressant therapy. The primary endpoint was change from randomisation to Week 6 in MADRS total score. Other assessments included MADRS response (≥ 50% decrease in total score) and remission (total score ≤ 8), change from randomisation in HAM-D, HAM-A, PSQI global and CGI-S scores. Results Quetiapine XR (150 and 300 mg/day) reduced MADRS total scores vs placebo at every assessment including Week 6 (− 14.5, − 14.8, − 12.0; p Limitations Fixed dosing; lack of active comparator. Conclusions Adjunctive Quetiapine XR is effective in patients with MDD and an inadequate response to antidepressant therapy, with improvement in depressive symptoms seen as early as Week 1.
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extended release Quetiapine fumarate Quetiapine xr as adjunctive therapy in major depressive disorder mdd in patients with an inadequate response to ongoing antidepressant treatment a multicentre randomized double blind placebo controlled study
The International Journal of Neuropsychopharmacology, 2010Co-Authors: Nizar Elkhalili, Catherine Datto, Mark Joyce, Sarah Atkinson, Robert Buynak, Petter Lindgren, Hans ErikssonAbstract:This study evaluated once-daily extended-release Quetiapine fumarate (Quetiapine XR) as adjunctive therapy in patients with major depressive disorder (MDD) with inadequate response to ongoing antidepressant treatment. In this 8-wk (6-wk active treatment/2-wk post-treatment drug-discontinuation/follow-up), multicentre, double-blind, placebo-controlled, Phase III study, 446 patients were randomized to Quetiapine XR 150 mg/d, 300 mg/d, or placebo adjunct to ongoing antidepressant treatment. The primary endpoint was the change from randomization to week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) total score. At week 6, MADRS total scores significantly improved with Quetiapine XR 300 mg/d vs. placebo (-14.7 vs. -11.7, p or = 50% total score reduction) 58.9% vs. 46.2%, p 10%) with Quetiapine XR were dry mouth, somnolence, sedation, dizziness, constipation, nausea, insomnia, headache, and fatigue. In this study, Quetiapine XR 300 mg/d as adjunctive therapy in patients with MDD with an inadequate response to ongoing antidepressant treatment was effective at week 6. However, the difference from placebo for Quetiapine XR 150 mg/d at week 6 was not statistically significant. Both doses studied (150 and 300 mg/d) were effective at week 1 and generally well tolerated.
Martin Brecher - One of the best experts on this subject based on the ideXlab platform.
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a double blind placebo controlled study of Quetiapine and paroxetine as monotherapy in adults with bipolar depression embolden ii
The Journal of Clinical Psychiatry, 2010Co-Authors: Susan L Mcelroy, Martin Brecher, Bjorn Paulsson, Richard H Weisler, William Chang, Bengt Olausson, Vasavan Agambaram, Charles H Merideth, Arvid Nordenhem, Allan H YoungAbstract:Objective The aim of this study was to evaluate the efficacy and tolerability of Quetiapine and paroxetine monotherapy for major depression in bipolar disorder. Method 740 patients (478 bipolar I, 262 bipolar II) with major depressive episodes (DSM-IV) were randomly assigned to Quetiapine 300 mg/d (n = 245), Quetiapine 600 mg/d (n = 247), paroxetine 20 mg/d (n = 122), or placebo (n = 126) for 8 weeks. The primary end point was the change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score. The study was conducted from May 2005 to May 2007. Results Mean MADRS score change from baseline at 8 weeks was -16.19 for Quetiapine 300 mg, -16.31 for Quetiapine 600 mg, -13.76 for paroxetine, and -12.60 for placebo (P Conclusions Quetiapine (300 or 600 mg/d), but not paroxetine, was more effective than placebo for treating acute depressive episodes in bipolar I and II disorder. Quetiapine treatment was generally well tolerated. Trial registration clinicaltrials.gov Identifier: NCT00119652.
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a double blind placebo controlled study of Quetiapine and lithium monotherapy in adults in the acute phase of bipolar depression embolden i
The Journal of Clinical Psychiatry, 2010Co-Authors: Allan H Young, Michael Bauer, Bjorn Paulsson, Susan L Mcelroy, William Chang, Bengt Olausson, Nabil Philips, Martin BrecherAbstract:OBJECTIVE The aim of this study was to compare the efficacy and tolerability of Quetiapine and lithium monotherapy with that of placebo for a major depressive episode in bipolar disorder. METHOD 802 patients with DSM-IV-defined bipolar disorder (499 bipolar I, 303 bipolar II) were randomly allocated to Quetiapine 300 mg/d (n = 265), Quetiapine 600 mg/d (n = 268), lithium 600 to 1800 mg/d (n = 136), or placebo (n = 133) for 8 weeks. Primary endpoint was the change in Montgomery-Asberg Depression Rating Scale (MADRS) total score. The study was conducted from August 2005 to May 2007. RESULTS Mean MADRS total score change from baseline at week 8 was -15.4 for Quetiapine 300 mg/d, -16.1 for Quetiapine 600 mg/d, -13.6 for lithium, and -11.8 for placebo (P < .001 for both Quetiapine doses, P = .123 for lithium, vs placebo). Quetiapine 600 mg/d was significantly more effective than lithium in improving MADRS total score at week 8 (P = .013). Quetiapine-treated (both doses), but not lithium-treated, patients showed significant improvements (P < .05) in MADRS response and remission rates, Hamilton Depression Rating Scale (HDRS), Clinical Global Impressions-Bipolar-Severity of Illness and -Change, and Hamilton Anxiety Rating Scale (HARS) scores at week 8 versus placebo. Both Quetiapine doses were more effective than lithium at week 8 on the HDRS and HARS. The most common adverse events were somnolence, dry mouth, and dizziness with Quetiapine (both doses) and nausea with lithium. CONCLUSIONS Quetiapine (300 or 600 mg/d) was more effective than placebo for the treatment of episodes of acute depression in bipolar disorder. Lithium did not significantly differ from placebo on the main measures of efficacy. Both treatments were generally well tolerated. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00206141.
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extended release Quetiapine fumarate monotherapy in major depressive disorder a placebo and duloxetine controlled study
The Journal of Clinical Psychiatry, 2009Co-Authors: Andrew J Cutler, S A Montgomery, David Feifel, Arthur Lazarus, Mikael Astrom, Martin BrecherAbstract:Objective: To evaluate the efficacy and tolerability of once-daily extended release Quetiapine fumarate (Quetiapine XR) as monotherapy treatment for major depressive disorder (MDD). Method: This 8-week (6-week active-treatment, randomized phase; 2-week posttreatment drug-discontinuation/tapering phase), multicenter, double-blind, randomized, parallel-group, placebo- and active-controlled, phase 3 study was conducted between April 2006 and May 2007. In total, 612 patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)-defined MDD were randomly assigned to Quetiapine XR 150 mg/day or 300 mg/day, duloxetine 60 mg/day (active control), or placebo. The primary endpoint was the change from baseline to week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) total score. Results: At week 6, both doses of Quetiapine XR (p <.001) and duloxetine (p <.01) significantly reduced mean MADRS total score versus placebo. A significant reduction was seen at week 1 with Quetiapine XR 150 mg/day and 300 mg/day versus placebo (p <.01), but not with duloxetine. Response rates (≥ 50% reduction in MADRS total score) at week 6 were significantly higher for both doses of Quetiapine XR (p <.01) and duloxetine (p <.05) versus placebo. Remission rates (MADRS score ≤ 8) were significantly higher for Quetiapine XR 300 mg/day and duloxetine versus placebo (p <.05), but not for Quetiapine XR 150 mg/day. Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, and Clinical Global Impressions-Severity of Illness total scores and the proportion of patients with Clinical Global Impressions-Improvement scores of 1 or 2 ("much/very much improved") were significantly improved with both doses of Quetiapine XR and duloxetine versus placebo. The most common adverse events reported were dry mouth, sedation, and somnolence for Quetiapine XR and nausea, headache, dizziness, and dry mouth for duloxetine. Conclusion: Quetiapine XR monotherapy (150 mg/day and 300 mg/day) is effective, with safety and tolerability consistent with the known profile of Quetiapine XR, in the treatment of patients with MDD, with onset of symptom improvement demonstrated at week 1.
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extended release Quetiapine as adjunct to an antidepressant in patients with major depressive disorder results of a randomized placebo controlled double blind study
The Journal of Clinical Psychiatry, 2009Co-Authors: Michael Bauer, Johan Szamosi, Willie Earley, Herman W Pretorius, Eric Constant, Martin BrecherAbstract:Objective: This 6-week, randomized, double-blind study evaluated efficacy and safety of adjunctive extended-re lease (XR) Quetiapine in patients with major depressive disorder (MDD) and an inadequate response to >= 1 antidepressant. Method: Male or female patients aged 18 to 65 years with DSM-IV-TR MDD were randomly assigned to receive Quetiapine XR (150 or 300 mg/day) or placebo adjunctive to continuing antidepressant. Primary endpoint was change from randomization to week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) total score. Secondary variables included MADRS response (>= 50% reduction in score from randomization) at weeks 1 and 6, MADRS remission (<= 8 total score) at week 6, and week 6 change in Hamilton Rating Scale for Depression and Hamilton Rating Scale for Anxiety total scores. Safety was assessed throughout the study. The study was conducted between May 8, 2006, and April 7, 2007. Results: Four hundred ninety-three patients were randomly assigned. Mean change from randomization to week 6 in MADRS score was -15.26 and -14.94 for Quetiapine XR 150 mg/day and 300 mg/day, respectively (both p <.01 vs. placebo [-12.21]). Quetiapine XR showed separation from placebo in MADRS score from week 1 (p < .001) onward. The MADRS response rates were 55.4%, 57.8%, and 46.3% for Quetiapine XR 150 mg/day (p = .107 vs. placebo), 300 mg/day (p < .05), and placebo, respectively; MADRS remission rates were 36.1% (p < .05 vs. placebo), 31.1% (p = .126), and 23.8% for Quetiapine XR 150 mg/day, 300 mg/day, and placebo, respectively. Withdrawal rates due to adverse events were 6.6%, 11.7%, and 3.7% with Quetiapine XR 150 mg/day, 300 mg/day, and placebo, respectively. The most common adverse events were dry mouth (20.4%, 35.6%, and 6.8%) and somnolence (16.8%, 23.3%, and 3.1%). Conclusions: Adjunctive Quetiapine XR (150 mg/day and 300 mg/day) was effective in patients with MDD who had shown an inadequate response to antidepressant treatment. Significant reduction of depressive symptoms occurred as early as week 1. Findings were consistent with the known safety and tolerability profile of Quetiapine.
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a 24 week multicenter open label randomized study to compare changes in glucose metabolism in patients with schizophrenia receiving treatment with olanzapine Quetiapine or risperidone
The Journal of Clinical Psychiatry, 2009Co-Authors: John W Newcomer, D Meulien, Robert E Ratner, Jan W Eriksson, Robin Emsley, Frank Miller, Julia Leonovaedlund, Ronald W Leong, Martin BrecherAbstract:Objective This randomized, 24-week, flexible-dose study compared changes in glucose metabolism in patients with DSM-IV schizophrenia receiving initial exposure to olanzapine, Quetiapine, or risperidone. Method The hypothesized primary endpoint was change (baseline to week 24) in area under the curve (AUC) 0- to 2-hour plasma glucose values during an oral glucose tolerance test (OGTT); primary analysis: olanzapine versus Quetiapine. Secondary endpoints included mean change in AUC 0- to 2-hour plasma insulin values, insulin sensitivity index, and fasting lipids. The first patient enrolled on April 29, 2004, and the last patient completed the study on October 24, 2005. Results Mean weight change (kg) over 24 weeks was +3.7 (Quetiapine), +4.6 (olanzapine), and +3.6 (risperidone). Based on data from 395 patients (Quetiapine, N = 115 [mean dose = 607.0 mg/day], olanzapine, N = 146 [mean dose = 15.2 mg/day], and risperidone, N = 134 [mean dose = 5.2 mg/day]), mean change in AUC 0- to 2-hour glucose value (mg/dL x h) at week 24 was significantly lower for Quetiapine versus olanzapine (t = 1.98, df = 377, p = .048). Increases in AUC 0- to 2-hour glucose values were statistically significant with olanzapine (+21.9 mg/dL x h, 95% CI = 11.5 to 32.4 mg/dL x h) and risperidone (+18.8 mg/dL x h, 95% CI = 8.1 to 29.4 mg/dL x h), but not Quetiapine (+9.1 mg/dL x h, 95% CI = -2.3 to 20.5 mg/dL x h). AUC 0- to 2-hour insulin values increased statistically significantly with olanzapine (+24.5%, 95% CI = 11.5% to 39.0%), but not with Quetiapine or risperidone. Reductions in insulin sensitivity index were statistically significant with olanzapine (-19.1%, 95% CI = -27.9% to -9.3%) and risperidone (-15.8%, 95% CI = -25.1% to -5.4%), but not Quetiapine. Total cholesterol and low-density lipoprotein levels increased statistically significantly with olanzapine (+21.1 mg/dL, 95% CI = 13.0 to 29.2 mg/dL, and +20.5 mg/dL, 95% CI = 13.8 to 27.1 mg/dL, respectively) and Quetiapine (+13.1 mg/dL, 95% CI = 4.3 to 21.9 mg/dL, and +13.3 mg/dL, 95% CI = 6.1 to 20.5 mg/dL, respectively), but not risperidone. Statistically significant increases in triglycerides (+30.9 mg/dL, 95% CI = 10.9 to 51.0 mg/dL), total cholesterol/high-density lipoprotein (HDL) ratio (0.5, 95% CI = 0.2 to 0.8), and triglyceride/HDL ratio (0.3, 95% CI = 0.0 to 0.6) were observed with olanzapine only. Conclusion The results indicate a significant difference in the change in glucose tolerance during 6 months' treatment with olanzapine versus Quetiapine, with significant reductions on olanzapine and risperidone, but not Quetiapine; these differential changes were largely explained by changes in insulin sensitivity. Trial registration clinicaltrials.gov Identifier: NCT00214578.
Catherine Datto - One of the best experts on this subject based on the ideXlab platform.
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efficacy and tolerability of extended release Quetiapine fumarate Quetiapine xr monotherapy in major depressive disorder a placebo controlled randomized study
Journal of Affective Disorders, 2011Co-Authors: Brian Bortnick, Nizar Elkhalili, Catherine Datto, Willie Earley, Michael Banov, David E Adson, Shane Raines, Hans ErikssonAbstract:Background Evaluate the efficacy and tolerability of extended release Quetiapine fumarate (Quetiapine XR) once-daily monotherapy for patients with major depressive disorder (MDD). Methods In this 10-week, (8-week active treatment phase and 2-week drug-discontinuation/tapering phase), multicenter, parallel-group, placebo-controlled, double-blind, randomized, Phase III study (D1448C00003: Opal), patients initially received Quetiapine XR 150 mg/day or placebo. At Week 2, inadequate responders (< 20% reduction in MADRS total score) were up-titrated to 300 mg/day Quetiapine XR or matching placebo for the final 6 weeks. Primary endpoint: change from randomization to Week 8 in MADRS total score. Secondary endpoints included: MADRS response (≥ 50% reduction in total score from randomization) and changes from randomization to Week 8 in HAM-D and CGI-S. Results 310 patients were randomized. At Week 8, Quetiapine XR significantly reduced mean MADRS total score versus placebo (−16.49 vs −13.10, respectively; p 10% any group during the randomized phase) for Quetiapine XR and placebo, respectively were dry mouth (32.9% and 6.5%), sedation (21.7% and 1.9%), somnolence (20.4% and 5.2%), and headache (10.5% and 10.3%). Limitations The study was not designed to compare Quetiapine XR 150 mg/day and 300 mg/day; it was intended to reflect dose titration that might occur in clinical practice. Conclusions Quetiapine XR monotherapy is effective in patients with MDD, with symptom improvement seen as early as Week 1, and tolerability results consistent with the known profile of Quetiapine.
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a pooled analysis of two randomised placebo controlled studies of extended release Quetiapine fumarate adjunctive to antidepressant therapy in patients with major depressive disorder
Journal of Affective Disorders, 2010Co-Authors: Michael Bauer, Nizar Elkhalili, Catherine Datto, Johan Szamosi, Hans ErikssonAbstract:Abstract Background Two positive studies evaluated adjunctive extended release Quetiapine fumarate (Quetiapine XR) in patients with major depressive disorder (MDD) showing inadequate response to antidepressant treatment. This preplanned, pooled analysis provides an opportunity for subgroup analyses investigating the influence of demographic and disease-related factors on observed responses. Additional post hoc analyses examined the efficacy of Quetiapine XR against specific depressive symptoms including sleep. Methods Data were analysed from two 6-week, multicentre, double-blind, randomised, placebo-controlled studies, prospectively designed to be pooled. Patients received once-daily Quetiapine XR 150 mg/day (n = 309), 300 mg/day (n = 307) or placebo (n = 303) adjunctive to ongoing antidepressant therapy. The primary endpoint was change from randomisation to Week 6 in MADRS total score. Other assessments included MADRS response (≥ 50% decrease in total score) and remission (total score ≤ 8), change from randomisation in HAM-D, HAM-A, PSQI global and CGI-S scores. Results Quetiapine XR (150 and 300 mg/day) reduced MADRS total scores vs placebo at every assessment including Week 6 (− 14.5, − 14.8, − 12.0; p Limitations Fixed dosing; lack of active comparator. Conclusions Adjunctive Quetiapine XR is effective in patients with MDD and an inadequate response to antidepressant therapy, with improvement in depressive symptoms seen as early as Week 1.
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efficacy and tolerability of extended release Quetiapine fumarate monotherapy as maintenance treatment of major depressive disorder a randomized placebo controlled trial
Depression and Anxiety, 2010Co-Authors: M Michael D Liebowitz, Catherine Datto, W Raymond M D Lam, Ulla Lepola, Dennis Sweitzer, M Hans B A ErikssonAbstract:Background: Primary objective: evaluate the efficacy (time to recurrence of depressive symptoms) of once daily extended release Quetiapine fumarate (Quetiapine XR) as maintenance monotherapy treatment to prevent relapse for major depressive disorder (MDD). Methods: Time-to-event (maximum 52 weeks), double-blind, multicenter, randomized withdrawal, placebo-controlled study of Quetiapine XR (50–300 mg/day) comprising four treatment phases: enrollment (up to 28 days), open-label run-in (4–8 weeks), open-label stabilization (12–18 weeks), and randomization (up to 52 weeks). Seven hundred and seventy-six patients stabilized on Quetiapine XR were eligible for randomization (Montgomery–Asberg Depression Rating Scale [MADRS] score ≤12 and Clinical Global Impression-Severity of Illness [CGI-S] score ≤3); 391 received Quetiapine XR and 385 received placebo (same dose as last open-label visit). Primary endpoint: time to recurrence of depressive event from randomization. Secondary outcomes included changes from randomization in MADRS total, CGI-S, Pittsburgh Sleep Quality Index (PSQI) global, and Hamilton Anxiety Rating Scale (HAM-A) total scores. Adverse events were recorded throughout. Results: Risk of recurrence of depressive event was significantly (P 10% any group) during the randomized period were headache and insomnia. Conclusions: Quetiapine XR maintenance therapy significantly reduced the risk of a depressive event in patients with MDD stabilized on Quetiapine XR, with a safety and tolerability profile consistent with the known profile of Quetiapine. Depression and Anxiety, 2010. © 2010 Wiley-Liss, Inc.
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extended release Quetiapine fumarate Quetiapine xr as adjunctive therapy in major depressive disorder mdd in patients with an inadequate response to ongoing antidepressant treatment a multicentre randomized double blind placebo controlled study
The International Journal of Neuropsychopharmacology, 2010Co-Authors: Nizar Elkhalili, Catherine Datto, Mark Joyce, Sarah Atkinson, Robert Buynak, Petter Lindgren, Hans ErikssonAbstract:This study evaluated once-daily extended-release Quetiapine fumarate (Quetiapine XR) as adjunctive therapy in patients with major depressive disorder (MDD) with inadequate response to ongoing antidepressant treatment. In this 8-wk (6-wk active treatment/2-wk post-treatment drug-discontinuation/follow-up), multicentre, double-blind, placebo-controlled, Phase III study, 446 patients were randomized to Quetiapine XR 150 mg/d, 300 mg/d, or placebo adjunct to ongoing antidepressant treatment. The primary endpoint was the change from randomization to week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) total score. At week 6, MADRS total scores significantly improved with Quetiapine XR 300 mg/d vs. placebo (-14.7 vs. -11.7, p or = 50% total score reduction) 58.9% vs. 46.2%, p 10%) with Quetiapine XR were dry mouth, somnolence, sedation, dizziness, constipation, nausea, insomnia, headache, and fatigue. In this study, Quetiapine XR 300 mg/d as adjunctive therapy in patients with MDD with an inadequate response to ongoing antidepressant treatment was effective at week 6. However, the difference from placebo for Quetiapine XR 150 mg/d at week 6 was not statistically significant. Both doses studied (150 and 300 mg/d) were effective at week 1 and generally well tolerated.
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effectiveness of the extended release formulation of Quetiapine as monotherapy for the treatment of acute bipolar depression
Journal of Affective Disorders, 2010Co-Authors: Trisha Suppes, Catherine Datto, Arvid Nordenhem, Margaret Minkwitz, Chris Walker, Denis DarkoAbstract:Background To evaluate the effectiveness of Quetiapine extended release once daily in bipolar depression. Methods Double-blind, placebo-controlled study in acutely depressed adults with bipolar I or II disorder, with or without rapid cycling. Patients were randomized to 8 weeks of Quetiapine extended release (XR) 300 mg daily monotherapy or placebo. The primary outcome measure was change from baseline to Week 8 in MADRS total score. Results Quetiapine XR 300 mg once daily (N = 133) showed significantly greater improvement in depressive symptoms compared with placebo (N = 137) from Week 1 (p < 0.001) through to Week 8 (p < 0.001). Mean change in MADRS total score at Week 8 was -17.4 in the Quetiapine XR group and -11.9 in the placebo group (p < 0.001). Response (≥ 50 reduction in MADRS total score) and remission (MADRS total score ≤ 12) rates at Week 8 were significantly higher with Quetiapine XR (p < 0.001) compared with placebo (p < 0.05). Quetiapine XR improved core symptoms of depression. The most common adverse events associated with Quetiapine XR were dry mouth, somnolence, and sedation. Greater weight gain was observed in patients on Quetiapine XR relative to placebo. Limitations Fewer patients with bipolar II disorder included, only one fixed dose tested and the lack of an active comparator. Conclusions Quetiapine XR (300 mg) once daily monotherapy was significantly more effective than placebo for treating episodes of depression in bipolar I disorder, throughout the 8-week study, with significance observed as early as Day 7. Adverse events were consistent with the known effects of Quetiapine.
Bjorn Paulsson - One of the best experts on this subject based on the ideXlab platform.
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continuation of Quetiapine versus switching to placebo or lithium for maintenance treatment of bipolar i disorder trial 144 a randomized controlled study
The Journal of Clinical Psychiatry, 2011Co-Authors: Willem A Nolen, Richard H Weisler, Anders Neijber, Asa Hellqvist, Bjorn PaulssonAbstract:Objective: Quetiapine, combined with lithium or divalproex, demonstrates efficacy in the maintenance treatment of bipolar I disorder. This study investigated the efficacy and safety of Quetiapine monotherapy as maintenance treatment in bipolar I disorder compared with switching to placebo or lithium. Method: Patients aged >= 18 years with DSM-IV-diagnosed bipolar I disorder and a current or recent manic, depressive, or mixed episode received open-label Quetiapine (300-800 mg/d) for 4-24 weeks. Patients achieving stabilization were randomized to continue Quetiapine or to switch to placebo or lithium (0.6-1.2 mEq/L) for up to 104 weeks in a double-blind trial. Outcome measures included times to recurrence of any mood event (primary outcome measure), manic event, or depressive event. Safety assessments included adverse events and laboratory values. The study was terminated early after planned interim analysis provided positive results. The study was conducted between March 2005 and July 2007. Results: Of 2,438 patients starting open-label Quetiapine, 1,226(50.3%) were randomized to double-blind treatment, including 1,172 (95.6%) in the intent-to-treat population. Time to recurrence of any mood event was significantly longer for Quetiapine versus placebo (hazard ratio [HR] = 0.29; 95% CI, 0.23-0.38; P <.0001) and for lithium versus placebo (HR = 0.46; 95% CI, 1136-0.59; P <.0001). Quetiapine and lithium significantly increased time to recurrence of both manic events (Quetiapine: HR = 0.29; 95% CI, 0.21-0.40; P <.0001; lithium: HR = 0.37; 95% CI, 0.27-0.53; P <.0001) and depressive events (Quetiapine: HR = 0.30; 95% CI, 0.20-0.44; P <.0001; lithium: HR = 0.59; 95% CI, 0.42-0.84; P <.004) compared with placebo. Overall rates of adverse events were generally similar between treatment groups, and safety findings for Quetiapine were consistent with its known profile. Conclusions: In patients stabilized during acute Quetiapine treatment, continuation of Quetiapine significantly increased time to recurrence of any mood, manic, or depressive event compared with switching to placebo. Switching to lithium was also more effective than placebo for the prevention of manic and depressive events.
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a double blind placebo controlled study of Quetiapine and paroxetine as monotherapy in adults with bipolar depression embolden ii
The Journal of Clinical Psychiatry, 2010Co-Authors: Susan L Mcelroy, Martin Brecher, Bjorn Paulsson, Richard H Weisler, William Chang, Bengt Olausson, Vasavan Agambaram, Charles H Merideth, Arvid Nordenhem, Allan H YoungAbstract:Objective The aim of this study was to evaluate the efficacy and tolerability of Quetiapine and paroxetine monotherapy for major depression in bipolar disorder. Method 740 patients (478 bipolar I, 262 bipolar II) with major depressive episodes (DSM-IV) were randomly assigned to Quetiapine 300 mg/d (n = 245), Quetiapine 600 mg/d (n = 247), paroxetine 20 mg/d (n = 122), or placebo (n = 126) for 8 weeks. The primary end point was the change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score. The study was conducted from May 2005 to May 2007. Results Mean MADRS score change from baseline at 8 weeks was -16.19 for Quetiapine 300 mg, -16.31 for Quetiapine 600 mg, -13.76 for paroxetine, and -12.60 for placebo (P Conclusions Quetiapine (300 or 600 mg/d), but not paroxetine, was more effective than placebo for treating acute depressive episodes in bipolar I and II disorder. Quetiapine treatment was generally well tolerated. Trial registration clinicaltrials.gov Identifier: NCT00119652.
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a double blind placebo controlled study of Quetiapine and lithium monotherapy in adults in the acute phase of bipolar depression embolden i
The Journal of Clinical Psychiatry, 2010Co-Authors: Allan H Young, Michael Bauer, Bjorn Paulsson, Susan L Mcelroy, William Chang, Bengt Olausson, Nabil Philips, Martin BrecherAbstract:OBJECTIVE The aim of this study was to compare the efficacy and tolerability of Quetiapine and lithium monotherapy with that of placebo for a major depressive episode in bipolar disorder. METHOD 802 patients with DSM-IV-defined bipolar disorder (499 bipolar I, 303 bipolar II) were randomly allocated to Quetiapine 300 mg/d (n = 265), Quetiapine 600 mg/d (n = 268), lithium 600 to 1800 mg/d (n = 136), or placebo (n = 133) for 8 weeks. Primary endpoint was the change in Montgomery-Asberg Depression Rating Scale (MADRS) total score. The study was conducted from August 2005 to May 2007. RESULTS Mean MADRS total score change from baseline at week 8 was -15.4 for Quetiapine 300 mg/d, -16.1 for Quetiapine 600 mg/d, -13.6 for lithium, and -11.8 for placebo (P < .001 for both Quetiapine doses, P = .123 for lithium, vs placebo). Quetiapine 600 mg/d was significantly more effective than lithium in improving MADRS total score at week 8 (P = .013). Quetiapine-treated (both doses), but not lithium-treated, patients showed significant improvements (P < .05) in MADRS response and remission rates, Hamilton Depression Rating Scale (HDRS), Clinical Global Impressions-Bipolar-Severity of Illness and -Change, and Hamilton Anxiety Rating Scale (HARS) scores at week 8 versus placebo. Both Quetiapine doses were more effective than lithium at week 8 on the HDRS and HARS. The most common adverse events were somnolence, dry mouth, and dizziness with Quetiapine (both doses) and nausea with lithium. CONCLUSIONS Quetiapine (300 or 600 mg/d) was more effective than placebo for the treatment of episodes of acute depression in bipolar disorder. Lithium did not significantly differ from placebo on the main measures of efficacy. Both treatments were generally well tolerated. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00206141.
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efficacy and safety of Quetiapine in combination with lithium or divalproex for maintenance of patients with bipolar i disorder international trial 126
Journal of Affective Disorders, 2008Co-Authors: Eduard Vieta, Bjorn Paulsson, Trisha Suppes, I Eggens, Inger Persson, Martin BrecherAbstract:Background This study examined the efficacy and safety of Quetiapine in combination with lithium or divalproex compared with placebo with lithium or divalproex in the prevention of recurrent mood events in bipolar I patients, most recent episode mania, depression, or mixed. Methods Patients received open-label Quetiapine (400–800 mg/day; flexible, divided doses) with lithium or divalproex (target serum concentrations 0.5–1.2 mEq/L and 50–125 μg/mL, respectively) for up to 36 weeks to achieve at least 12 weeks of clinical stability. Patients were subsequently randomized to double-blind treatment with Quetiapine (400–800 mg/day) plus lithium/divalproex or placebo plus lithium/divalproex for up to 104 weeks. The primary endpoint was time to recurrence of any mood event. Results Treatment with Quetiapine in combination with lithium/divalproex significantly increased the time to recurrence of any mood event compared with placebo plus lithium/divalproex. The proportion of patients having a mood event was markedly lower in the Quetiapine than in the placebo group (18.5% versus 49.0%). The hazard ratio for time to recurrence of a mood event was 0.28 (P < 0.001), a mania event 0.30 (P < 0.001), and a depression event 0.26 (P < 0.001) corresponding to risk reductions of 72%, 70%, and 74%, respectively. During the randomization phase, the most common adverse events occurring in ≥ 5% in the Quetiapine group were somnolence, nasopharyngitis, and headache. Insomnia was more common in the placebo group. During the randomization phase, there was an increase in weight of 0.5 kg in the Quetiapine group and a reduction of 1.9 kg in the placebo group. The incidence and incidence density of a single emergent fasting blood glucose value ≥ 126 mg/dL was higher with Quetiapine than with placebo (9.3% versus 4.1%; 17.6 versus 9.5 patients per 100 patient-years). Limitations This was an enriched sample of patients with bipolar I disorder responding to treatment with Quetiapine plus lithium/divalproex. Conclusions Maintenance treatment with Quetiapine in combination with lithium/divalproex significantly increased time to recurrence of any event (mania, depression, or mixed) irrespective of the polarity of the index episode compared with placebo with lithium/divalproex. Long-term treatment with Quetiapine was generally well-tolerated. Quetiapine with lithium/divalproex can provide an effective long-term treatment option for bipolar I disorder to prevent recurrences not only of mania but also depression.
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placebo level incidence of extrapyramidal symptoms eps with Quetiapine in controlled studies of patients with bipolar mania
Bipolar Disorders, 2006Co-Authors: Henry A Nasrallah, Martin Brecher, Bjorn PaulssonAbstract:Objectives: To evaluate extrapyramidal symptoms (EPS), including akathisia, with Quetiapine in patients with bipolar mania. Methods: Data were analyzed from four similarly designed, randomized, double-blind, 3- to 12-week studies. Two studies evaluated Quetiapine monotherapy (up to 800 mg/day) (n = 209) versus placebo (n = 198), with lithium or haloperidol monotherapy as respective active controls. Two studies evaluated Quetiapine (up to 800 mg/day) in combination with a mood stabilizer (lithium or divalproex, QTP + Li/DVP) (n = 196) compared to placebo and mood stabilizer (PBO + Li/DVP) (n = 203). Extrapyramidal symptoms were evaluated using the Simpson–Angus Scale (SAS), the Barnes Akathisia Rating Scale (BARS), adverse event reports and anticholinergic drug usage. Results: The incidence of EPS-related adverse events, including akathisia, was no different with Quetiapine monotherapy (12.9%) than with placebo (13.1%). Similarly, EPS-related adverse events with QTP + Li/DVP (21.4%) were no different than with PBO + Li/DVP (19.2%). Adverse events related to EPS occurred in 59.6% of patients treated with haloperidol (n = 99) monotherapy, whereas 26.5% of patients treated with lithium (n = 98) monotherapy experienced adverse events related to EPS. The incidence of akathisia was low and similar with Quetiapine monotherapy (3.3%) and placebo (6.1%), and with QTP + Li/DVP (3.6%) and PBO + Li/DVP (4.9%). Lithium was associated with a significantly higher incidence (p < 0.05) of tremor (18.4%) than Quetiapine (5.6%); cerebellar tremor, which is a known adverse effect of lithium, may have contributed to the elevated rate of tremor in patients receiving lithium therapy. Haloperidol induced a significantly higher incidence (p < 0.001) of akathisia (33.3% versus 5.9%), tremor (30.3% versus 7.8%), and extrapyramidal syndrome (35.4% versus 5.9%) than Quetiapine. No significant differences were observed between Quetiapine and placebo on SAS and BARS scores. Anticholinergic use was low and similar with Quetiapine or placebo. Conclusions: In bipolar mania, the incidence of EPS, including akathisia, with Quetiapine therapy is similar to that with placebo.
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pooled analysis of adjunct extended release Quetiapine fumarate in patients with major depressive disorder according to ongoing ssri or snri treatment
International Clinical Psychopharmacology, 2014Co-Authors: Michael Bauer, Nizar Elkhalili, Johan Szamosi, Willie Earley, Koen Demyttenaere, Michael E Thase, George I Papakostas, Hans ErikssonAbstract:This pooled analysis evaluated the efficacy of extended-release Quetiapine fumarate (Quetiapine XR) adjunct to selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) in patients with major depressive disorder (MDD). Pooled data were analyzed from two 6-week, double-blind, randomized, placebo-controlled trials of adjunct Quetiapine XR (150 and 300 mg/day) in patients with MDD and inadequate response to initial antidepressant monotherapy. This post-hoc analysis included evaluation of change from randomization at week 6 in Montgomery Asberg Depression Rating Scale (MADRS) total scores (primary endpoint), and week 6 MADRS response and remission rates for Quetiapine XR as an adjunct to ongoing SSRI or SNRI. In total, 189, 178, and 202 patients received Quetiapine XR 150 mg/day+SSRI, 300 mg/day+SSRI, and placebo+SSRI, respectively, whereas 82, 90, and 76 patients, respectively, received Quetiapine XR 150 mg/day+SNRI, 300 mg/day+SNRI, and placebo+SNRI. At week 6, Quetiapine XR 150 mg/day+SSRI and 300 mg/day+SSRI reduced the MADRS total score from randomization versus placebo+SSRI [least squares mean (LSM) change, -14.70 (P<0.05) -14.72 (P<0.05) vs. -12.59, respectively]. Quetiapine XR 150 mg/day+SNRI (LSM change, -14.68, P<0.01) and 300 mg/day+SNRI (LSM change, -14.99, P<0.01) also reduced the MADRS total score from randomization at week 6 versus placebo+SNRI (-10.77). In conclusion, in patients with MDD and inadequate response to ongoing antidepressant, adjunct Quetiapine XR (150 and 300 mg/day) was effective in both SSRI and SNRI subgroups.
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evaluation of the effects of extended release Quetiapine fumarate monotherapy on sleep disturbance in patients with major depressive disorder a pooled analysis of four randomized acute studies
The International Journal of Neuropsychopharmacology, 2013Co-Authors: Madhukar H. Trivedi, Johan Szamosi, Willie Earley, Borwin Bandelow, Koen Demyttenaere, George I Papakosts, Hans ErikssonAbstract:Effects of once-daily extended-release Quetiapine fumarate (Quetiapine XR) monotherapy on sleep quality and disturbance in patients with major depressive disorder (MDD) were evaluated. Pooled data from four 6- or 8-wk placebo-controlled Quetiapine XR (50-300 mg/d) monotherapy studies (D1448C00001; D1448C00002; D1448C00003; D1448C00004) were analysed. Primary efficacy end-point was change from randomization in Montgomery Asberg Depression Rating Scale (MADRS) score. Post hoc analyses of secondary end-points were conducted for change from randomization in: MADRS item 4 (reduced sleep); Hamilton Rating Scale for Depression (HAMD) items 4 (insomnia-early), 5 (insomnia-middle), 6 (insomnia-late) and sleep disturbance factor (items 4 + 5+6) scores; Pittsburgh Sleep Quality Index (PSQI) global scores. MADRS total score change was also evaluated in patients experiencing high and low baseline sleep disturbance (HAMD sleep disturbance factor scores ⩾4 and < 4, respectively). In total, 1808 patients were randomized to Quetiapine XR or placebo across four studies. At last assessment, Quetiapine XR reduced MADRS item 4, HAMD items 4, 5 and 6, HAMD sleep disturbance factor score and PSQI global scores from baseline vs. placebo (p < 0.001). For those experiencing high sleep disturbance (n = 865, Quetiapine XR; n = 514, placebo), Quetiapine XR improved MADRS total score vs. placebo at all visits (p < 0.001). For those with low sleep disturbance (n = 252, Quetiapine XR; n = 121, placebo), Quetiapine XR improved MADRS total score vs. placebo at weeks 2 (p < 0.001), 4 and 6 (both p < 0.05). In conclusion, Quetiapine XR (50-300 mg/d) monotherapy improved symptoms of sleep disturbance vs. placebo in patients with MDD, including those with either high or low baseline sleep disturbance levels.
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pharmacokinetic profile of the extended release formulation of Quetiapine fumarate Quetiapine xr clinical implications
Current Medical Research and Opinion, 2013Co-Authors: Willie Earley, Svante NybergAbstract:AbstractObjectives:A series of studies were conducted to guide the development and characterise the pharmacokinetics of extended-release Quetiapine fumarate (Quetiapine XR), a once-daily formulation to control the release of the drug.Methods:Data from these studies are described and discussed herein.Results:Once-daily Quetiapine XR produced a similar area under the plasma concentration–time curve (AUC), minimum plasma concentration (Cmin) and a slightly lower maximum plasma concentration (Cmax) than the equivalent dose of immediate-release Quetiapine (Quetiapine IR) given twice daily. In a crossover, head-to-head study, total daily exposure, measured by AUC at steady state, was less variable with Quetiapine XR versus Quetiapine IR (percent coefficient of variation 39.2% versus 51.2%, respectively). Compared with fasting, a high-fat meal increased the AUC and Cmax for Quetiapine XR, whereas a light meal had no significant effect on these parameters. Quetiapine XR exhibits a less pronounced D2 receptor occu...
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efficacy and safety of Quetiapine in children and adolescents with mania associated with bipolar i disorder a 3 week double blind placebo controlled trial
The Journal of Clinical Psychiatry, 2013Co-Authors: Sanjeev Pathak, Willie Earley, Robert L Findling, Larisa D Acevedo, Jill Stankowski, Melissa P. DelbelloAbstract:OBJECTIVE To evaluate the efficacy and safety of Quetiapine monotherapy in children and adolescents with mania associated with bipolar I disorder. METHOD Patients aged 10 to 17 years, with a DSM-IV-TR diagnosis of a manic episode associated with bipolar I disorder and Young Mania Rating Scale (YMRS) total score ≥ 20 were randomized to 3 weeks of Quetiapine (400 or 600 mg/d) or placebo. The primary efficacy measure was change in YMRS total score. The study was conducted at 34 centers in the United States between August 2004 and July 2006. RESULTS The intent-to-treat population included 277 patients. Least squares mean change in YMRS score from baseline to end point by mixed-model, repeated-measures analysis was -14.25, -15.60, and -9.04 for Quetiapine 400 mg/d, Quetiapine 600 mg/d, and placebo, respectively (P < .001, each Quetiapine dose vs placebo). Significant improvement in YMRS score versus placebo was first observed at day 4 (P = .015) with Quetiapine 400 mg/d and day 7 (P < .001) with Quetiapine 600 mg/d. Mean changes in body weight at day 21 (observed cases) were 1.7 kg for both Quetiapine doses and 0.4 kg for placebo. Numerically larger mean increases in total cholesterol, low-density lipoprotein cholesterol, and triglycerides were observed with Quetiapine than placebo. Adverse events associated with Quetiapine were mostly mild to moderate in intensity. CONCLUSIONS In this 3-week study, Quetiapine was significantly more effective than placebo in improving manic symptoms in youth with mania associated with bipolar disorder. Treatment was generally well tolerated and adverse events were broadly consistent with the known profile of Quetiapine in adults with bipolar disorder. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT00090311.
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efficacy and tolerability of extended release Quetiapine fumarate Quetiapine xr monotherapy in major depressive disorder a placebo controlled randomized study
Journal of Affective Disorders, 2011Co-Authors: Brian Bortnick, Nizar Elkhalili, Catherine Datto, Willie Earley, Michael Banov, David E Adson, Shane Raines, Hans ErikssonAbstract:Background Evaluate the efficacy and tolerability of extended release Quetiapine fumarate (Quetiapine XR) once-daily monotherapy for patients with major depressive disorder (MDD). Methods In this 10-week, (8-week active treatment phase and 2-week drug-discontinuation/tapering phase), multicenter, parallel-group, placebo-controlled, double-blind, randomized, Phase III study (D1448C00003: Opal), patients initially received Quetiapine XR 150 mg/day or placebo. At Week 2, inadequate responders (< 20% reduction in MADRS total score) were up-titrated to 300 mg/day Quetiapine XR or matching placebo for the final 6 weeks. Primary endpoint: change from randomization to Week 8 in MADRS total score. Secondary endpoints included: MADRS response (≥ 50% reduction in total score from randomization) and changes from randomization to Week 8 in HAM-D and CGI-S. Results 310 patients were randomized. At Week 8, Quetiapine XR significantly reduced mean MADRS total score versus placebo (−16.49 vs −13.10, respectively; p 10% any group during the randomized phase) for Quetiapine XR and placebo, respectively were dry mouth (32.9% and 6.5%), sedation (21.7% and 1.9%), somnolence (20.4% and 5.2%), and headache (10.5% and 10.3%). Limitations The study was not designed to compare Quetiapine XR 150 mg/day and 300 mg/day; it was intended to reflect dose titration that might occur in clinical practice. Conclusions Quetiapine XR monotherapy is effective in patients with MDD, with symptom improvement seen as early as Week 1, and tolerability results consistent with the known profile of Quetiapine.
