Once-daily Extended Release Quetiapine Fumarate Research Articles

Impact of once-daily extended-release quetiapine fumarate on hospitalization length in patients with acute bipolar mania.

Evaluate the impact of quetiapine extended release (XR) versus quetiapine immediate release (IR) on hospitalization length in acute bipolar mania using Truven Health Analytics MarketScan Hospital Drug Database. Generalized linear model analyses were used, adjusting for patient and hospital characteristics. Using data from 3088 discharges, quetiapine XR reduced hospitalization length by 6.7% versus quetiapine IR (p = 0.11; no statistically significant differences between groups), corresponding to 0.6 fewer days in hospital. Excluding the outlier, quetiapine XR significantly reduced hospitalization length by 9.6% versus quetiapine IR (p = 0.02), corresponding to 0.9 days. Inpatient use of quetiapine XR in acute bipolar mania may be associated with reduced hospitalization length (7-10%), possibly owing to the faster titration schedule versus quetiapine IR.

Efficacy of once-daily extended release quetiapine fumarate in patients with different levels of severity of generalized anxiety disorder

This study is a pooled, post-hoc analysis evaluating once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in patients with generalized anxiety disorder (GAD). Three previously reported positive, 8-week, randomized, double-blind, placebo-controlled studies evaluated quetiapine XR therapy (50, 150, 300 mg/day) in patients with GAD [Hamilton Anxiety Rating Scale (HAM-A) total score ≥ 20]. Patients were stratified by baseline severity: HAM-A total score ≥ 22, ≥ 24, < 26, ≥ 26, ≥ 28. We report HAM-A total score change, response (≥ 50% reduction in HAM-A total score), and remission (HAM-A total score ≤ 7 and ≤ 9). Quetiapine XR significantly improved HAM-A total scores compared with placebo at Weeks 1 and 8 in the HAM-A ≥ 22, ≥ 24, and ≥ 26 cohorts (all doses), at Week 1 (all doses) and Week 8 (quetiapine XR 150 mg/day) in the < 26 cohort, and at Week 1 (all doses) and Week 8 (quetiapine XR 50 and 150 mg/day) in the HAM-A ≥ 28 group (P<0.05). Week 8 effect sizes for 50, 150, and 300 mg/day were as follows: 0.29, 0.47, 0.17 (HAM-A ≥ 22); 0.35, 0.55, 0.22 (HAM-A ≥ 24); 0.18, 0.32, 0.10 (HAM-A < 26); 0.41, 0.59, 0.24 (HAM-A ≥ 26); 0.60, 0.64, 0.22 (HAM-A ≥ 28), respectively. Acute quetiapine XR monotherapy significantly improves anxiety compared with placebo in patients with moderate or severe GAD, with symptom improvements seen as early as Week 1.

A randomized, double-blind study of the efficacy and tolerability of extended-release quetiapine fumarate (quetiapine XR) monotherapy in patients with major depressive disorder.

ObjectivesTo evaluate the efficacy and tolerability of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in patients with major depressive disorder (MDD).Patients and methodsThis was a 10-week (8-week active treatment/2-week post-treatment) randomized, double-blind, placebo- and active-controlled study (D1448C00004). Patients received quetiapine XR 150 mg/day, escitalopram 10 mg/day, or placebo; patients with an inadequate response (<20% improvement in Montgomery–Åsberg Depression Rating Scale [MADRS] total score) at week two received double-dose treatment. The primary end point was week eight change from randomization in MADRS total score. Secondary end points included MADRS response (≥50% improvement) and remission (score ≤8); Hamilton Rating Scale for Depression total and item 1; Hamilton Rating Scale for Anxiety total, psychic, and somatic; Clinical Global Impressions – Severity of Illness total; Pittsburgh Sleep Quality Index (PSQI) global; and Quality of Life Enjoyment and Satisfaction Questionnaire – Short Form percentage maximum total scores. Tolerability was assessed throughout.ResultsA total of 471 patients was randomized. No significant improvements in MADRS total score were observed at week eight (last observation carried forward) with either active treatment (quetiapine XR, −17.21 [P=0.174]; escitalopram, −16.73 [P=0.346]) versus placebo (−15.61). There were no significant differences in secondary end points versus placebo, with the exception of week-eight change in PSQI global score (quetiapine XR, −4.96 [P<0.01] versus placebo, −3.37). Mixed-model repeated-measures analysis of observed-case data suggested that the primary analysis may not be robust. Most commonly reported adverse events included dry mouth, somnolence, and dizziness for quetiapine XR, and headache and nausea for escitalopram.ConclusionIn this study, neither quetiapine XR (150/300 mg/day) nor escitalopram (10/20 mg/day) showed significant separation from placebo. Both compounds have been shown previously to be effective in the treatment of MDD; possible reasons for this failed study are discussed. Quetiapine XR was generally well tolerated, with a profile similar to that reported previously.

Sexual functioning in patients with major depressive disorder in randomized placebo-controlled studies of extended release quetiapine fumarate

We evaluated sexual functioning from 6 acute, randomized, placebo-controlled studies (6-10 weeks) of once-daily extended release quetiapine fumarate (quetiapine XR) 50, 150, or 300 mg/day as monotherapy (Studies 1-4) or adjunct therapy (Studies 6-7) in major depressive disorder (MDD). We present a pre-planned, non-inferiority analysis of quetiapine XR monotherapy versus placebo using Changes in Sexual Functioning Questionnaire (CSFQ) total score change (Studies 1-4). Post hoc analyses evaluated CSFQ total and domain scores for fixed-dose monotherapy (Studies 1-2), modified fixed-dose (Studies 3-4), and adjunct therapy studies (Studies 6-7). CSFQ data for active comparators (duloxetine [Study 2], escitalopram [Study 4]) are reported. Quetiapine XR monotherapy was non-inferior to placebo for sexual functioning (least squares mean [LSM] difference in CSFQ score change versus placebo, 0.16 [95% confidence interval: -0.59, 0.92]); LSM change in CSFQ score: 1.90, quetiapine XR (all doses) and 1.73, placebo. LSM differences versus placebo (95% confidence interval): 0.18 (-1.40, 1.75), duloxetine (Study 2); 0.16 (-1.77, 2.10), escitalopram (Study 4). LSM differences with adjunct quetiapine XR 150 mg/day (0.52; p = 0.338) or 300 mg/day (0.22; p = 0.679) were comparable with placebo plus antidepressants. Post hoc all-patient and gender-specific analyses were comparable for CSFQ total scores versus placebo with quetiapine XR 50, 150, or 300 mg/day, duloxetine, and escitalopram. Discussion Lack of negative effects on sexual functioning in patients with MDD may improve treatment acceptability. Quetiapine XR (monotherapy or adjunct therapy) had an impact on sexual function that was comparable with placebo.

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

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 (50-300mg/d) monotherapy studies (D1448C00001; D1448C00002; D1448C00003; D1448C00004) were analysed. Primary efficacy end-point was change from randomization in Montgomery Åsberg 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 (50-300mg/d) monotherapy improved symptoms of sleep disturbance vs. placebo in patients with MDD, including those with either high or low baseline sleep disturbance levels.

Extended-release quetiapine fumarate (quetiapine XR) monotherapy and quetiapine XR or lithium as add-on to antidepressants in patients with treatment-resistant major depressive disorder

BackgroundPatients with treatment-resistant major depressive disorder (MDD) remain a common clinical challenge. MethodsThis 6-week, randomised, open-label, rater-blinded trial evaluated once-daily extended-release quetiapine fumarate (quetiapine XR; 300mg/day) as add-on to ongoing antidepressant and quetiapine XR monotherapy (300mg/day) compared with add-on lithium (0.6–1.2mmol/L) in patients with treatment-resistant MDD. Primary efficacy measure: change in Montgomery Åsberg Depression Rating Scale (MADRS) total score from randomisation to week 6 with a pre-specified non-inferiority limit of 3 points on the MADRS. ResultsAt week 6, both add-on quetiapine XR (n=231) and quetiapine XR monotherapy (n=228) were non-inferior to add-on lithium (n=229); least squares means (LSM) differences (97.5% CI) in MADRS total score changes were −2.32 (−4.6, −0.05) and −0.97 (−3.24, 1.31), respectively. LSM MADRS total score change was numerically greater at day 4 for both quetiapine XR groups (add-on and monotherapy; p<0.01) compared with add-on lithium. At week 6, the differences between groups for the secondary endpoints of MADRS response (≥50% reduction in total score), MADRS remission (total score ≤10, add-on quetiapine XR only) and Clinical Global Impressions (‘much’/‘very much’ improved) were numerically similar. Overall tolerability was consistent with the known profiles of both treatments. LimitationsLimitations included the open-label study design (although MADRS and laboratory measurements were performed by treatment-blinded raters) and relatively short study duration with no assessments in the continuation phase. ConclusionsAdd-on quetiapine XR (300mg/day) and quetiapine XR monotherapy (300mg/day) are non-inferior to add-on lithium in the management of patients with treatment-resistant MDD.

Effects of once-daily extended release quetiapine fumarate (quetiapine XR) on quality of life and sleep in elderly patients with major depressive disorder

BackgroundMajor depressive disorder (MDD) is frequently associated with reduced quality of life (QoL) and sleep disturbance. We investigated the effects of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy on QoL and sleep in elderly patients with MDD. MethodsProspectively planned analysis of patient-reported data from an 11-week (9-week randomized; 2-week post-treatment), double-blind, placebo-controlled, Phase III study. Elderly patients (≥66 years; DSM-IV MDD; Hamilton Rating Scale for Depression [HAM-D] total score ≥22, HAM-D Item 1 score ≥2) were randomized to quetiapine XR (flexible dosing 50–300mg/day) or placebo. Primary outcome: MADRS total score change from randomization at Week 9. Patient-reported outcomes: Quality of Life, Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) % of maximum total score (Items 1–14), Q-LES-Q-SF Item 15 (‘satisfaction with medication’), Q-LES-Q-SF Item 16 (‘overall life satisfaction’), and Pittsburgh Sleep Quality Index (PSQI) global score. ResultsIn total, 338 patients were randomized (166 quetiapine XR; 172 placebo). At Week 9, quetiapine XR significantly reduced MADRS total score (−16.33; difference: −7.54; 95% CI: −9.23, −5.85; p<0.001) versus placebo (−8.79). Quetiapine XR significantly improved Q-LES-Q-SF % of maximum total score (16.86; difference: 7.69; 95% CI: 4.99, 10.39; p<0.001) versus placebo (9.17), with numerical improvement in Q-LES-Q-SF Item 15 and improvement in Item 16. Improvement in PSQI global score was observed with quetiapine XR (-6.42; difference: −3.52; 95% CI: −4.26, −2.79; p<0.001) versus placebo (−2.89). LimitationsLack of active-comparator arm, flexible-dose design, acute treatment period. ConclusionsQuetiapine XR monotherapy improved QoL and sleep in elderly patients with MDD.

Randomized, Double-Blind Study of the Efficacy and Tolerability of Extended Release Quetiapine Fumarate (Quetiapine XR) Monotherapy in Elderly Patients with Major Depressive Disorder

This study assessed the efficacy and tolerability of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in elderly patients with major depressive disorder (MDD). An 11-week (9-week randomized; 2-week posttreatment phase), double-blind, placebo-controlled, Phase III study (D1448C00014). A total of 53 centers in Argentina, Estonia, Finland, Russia, Ukraine, and the United States. A total of 338 patients (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of MDD, age≥66 years, Hamilton Rating Scale for Depression [HAM-D] total score≥22, HAM-D Item 1 [depressed mood] score≥2) were randomized (mean age: 71.3 years). Patients were randomized to quetiapine XR (n= 166; flexible-dosing 50-300 mg/day) or placebo (n= 172). Primary outcome was Montgomery Åsberg Depression Rating Scale (MADRS) total score change from randomization at Week9. At Week 9, quetiapine XR (least squares [LS] means:-16.33, standard error [SE]: 0.95; mean change:-16.0, standard deviation [SD]: 9.3) significantly reduced MADRS total score from randomization versus placebo (LS means [SE]:-8.79 [0.94]; mean [SD]:-9.0 [9.9]); significant improvements were also seen at Week 1 (LS means [SE]:-4.65 [0.53] versus-2.56 [0.53], respectively; mean [SD]:-4.3 [5.1] versus-2.4 [3.7], respectively). At Week 9, secondary outcome variables significantly improved with quetiapine XR versus placebo, including MADRS response (≥50% reduction in total score); MADRS remission (total score≤8); HAM-D total, HAM-A total, HAM-A psychic and somatic cluster, and Clinical Global Impressions-Severity of Illness (CGI-S) total scores; proportion of patients with CGI-Improvement score of 2 or less; Q-LES-Q-SF% maximum total, Pittsburgh Sleep Quality Index global, and pain Visual Analog Scale scores. Common adverse events (>10% patients with quetiapine XR) were somnolence, headache, dry mouth, and dizziness. In elderly patients with MDD, quetiapine XR monotherapy (50-300 mg/day, flexibly dosed) is effective at improving depressive symptoms, with symptom improvement observed as early as Week 1. Overall tolerability and safety were consistent with the known profile of quetiapine.

EXTENDED RELEASE QUETIAPINE FUMARATE IN MAJOR DEPRESSIVE DISORDER: ANALYSIS IN PATIENTS WITH ANXIOUS DEPRESSION

A pooled analysis was performed on data from two studies evaluating the efficacy of once-daily extended-release quetiapine fumarate (quetiapine XR) monotherapy for patients with major depressive disorder. Through these analyses (based on Hamilton Rating Scale for Depression (HAM-D) and Hamilton Rating Scale for Anxiety (HAM-A) measures), we aim to further evaluate the efficacy of quetiapine XR in depressed patients with high levels of anxiety symptoms. Secondary analyses were conducted of pooled individual patient data from two 8-week (6-week randomized phase, 2-week drug discontinuation phase), double-blind, placebo-controlled studies of quetiapine XR (50-300 mg/day). Outcomes included change from randomization at Week 6 in Montgomery Åsberg Depression Rating Scale (MADRS) total score for patients with anxious and nonanxious depression. Of 968 patients included in the analysis, 788 (81.4%) were classified as anxious depressed (defined as HAM-D anxiety/somatization factor score ≥ 7) and 180 (18.6%) were nonanxious. For patients with anxious depression and nonanxious depression, statistically significant differences versus placebo in MADRS total score were recorded for quetiapine XR 150 mg/day (-3.24, P < .001 and -4.82, P < .01, respectively) and 300 mg/day (-3.57, P < .001 and -3.39, P < .05, respectively) at Week 6. In the second analysis using an alternate definition of anxious depression (baseline HAM-A total score ≥ 20), quetiapine XR 150 and 300 mg/day resulted in significant differences versus placebo in MADRS total score reduction in patients with high and lower levels of anxiety. The adverse event (AE) profile was similar irrespective of baseline anxiety levels, although patients with anxious depression reported a somewhat greater incidence of AEs. Quetiapine XR monotherapy improved symptoms of depression in patients with higher and lower levels of anxiety.

Efficacy and tolerability of extended release quetiapine fumarate monotherapy in the acute treatment of generalized anxiety disorder

The main objective of this study was to evaluate efficacy and tolerability of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in generalized anxiety disorder (GAD). This was a 8 week randomized, 2-week follow-up, double-blind, placebo-controlled, and active-controlled study. Patients were randomized to quetiapine XR 150 (n=219) or 300 mg/day (n=207); escitalopram, 10 mg/day (n=213); or placebo (n=215). The primary endpoint was the change from randomization at week 8 in Hamilton Anxiety Rating (HAM-A) total score. Week 8 mean HAM-A total score was significantly reduced from randomization with quetiapine XR 150 mg/day (-13.9, P<0.001), 300 mg/day (-12.3, P<0.05) and escitalopram (-12.3, P<0.05) versus placebo (-10.7); significant improvements with quetiapine XR (150 and 300 mg/day) versus placebo (P<0.001) were also shown at day 4. At week 8, significant improvements versus placebo were observed in HAM-A psychic [quetiapine XR (both doses) and escitalopram] and somatic (quetiapine XR 150 mg/day and escitalopram) cluster scores and HAM-A response and remission rates (quetiapine XR 150 mg/day). Most common adverse events were dry mouth, somnolence and sedation (quetiapine XR), headache, and nausea (escitalopram). In patients with GAD, quetiapine XR (150 and 300 mg/day) demonstrated significant efficacy at week 8 with symptom improvement as early as day 4. We concluded that quetiapine XR safety and tolerability results were consistent with the known profile of quetiapine.

Effects of once-daily extended release quetiapine fumarate on patient-reported outcomes in patients with generalized anxiety disorder.

BackgroundWe evaluated the effects of once-daily extended-release quetiapine fumarate (quetiapine XR) on patient-reported outcomes in generalized anxiety disorder (GAD).MethodsThis is a report of a pooled analysis from three acute 8-week, randomized, placebocontrolled, fixed-dose (50, 150, 300 mg/day) studies and a 52-week maintenance flexible dose (50–300 mg/day) study of quetiapine XR monotherapy in patients with GAD. Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) percent maximum total scores (items 1–14), item 15 (“satisfaction with medication”), item 16 (“overall life satisfaction”), and Pittsburgh Sleep Quality Index (PSQI) global scores are reported. Sheehan Disability Scale (SDS) total scores were also assessed (maintenance study only).ResultsThe acute studies showed significant improvements at week 8 in Q-LES-Q-SF percent maximum total score with quetiapine XR 150 mg/day (P < 0.001) and item 16 with quetiapine XR 50 (P < 0.05) and 150 mg/day (P < 0.001) versus placebo; PSQI global scores significantly improved with quetiapine XR 50, 150, and 300 mg/day versus placebo (P < 0.001). The maintenance study showed significant benefits versus placebo with quetiapine XR 50–300 mg/day in Q-LES-Q-SF percent total score, item 15 and item 16 scores, PSQI global score, and SDS total score.ConclusionQuetiapine XR 150 mg/day (acute studies) and 50–300 mg/day (maintenance study) improved quality of life, overall functioning, and sleep quality in patients with GAD.

Extended-Release Quetiapine as Monotherapy for the Treatment of Adults With Acute Mania: A Randomized, Double-Blind, 3-Week Trial

Background Bipolar disorder, a highly recurrent and chronic condition, often necessitates periods of hospitalization and requires lifelong treatment with medication. It is characterized by alternating episodes of mania and depression. Given the severity of mania, physicians must be able to control symptoms rapidly. Objective The purpose of this pivotal, Phase III trial was to evaluate the efficacy and tolerability of once-daily extended-release quetiapine fumarate (quetiapine XR) monotherapy in improving manic symptoms in patients with bipolar I disorder. Methods This was a 3-week, randomized, parallel-group, double-blind, placebo-controlled study. Patients aged 18 to 65 years with bipolar I disorder (most recent episode manic or mixed; with or without rapid cycling) were randomized to receive placebo or quetiapine XR monotherapy once daily (300 mg on day 1; 600 mg on day 2; flexible dosing, 400–800 mg, from day 3 through day 22 [study end point, week 3]). The primary outcome measure was the change from baseline to study end in the Young Mania Rating Scale (YMRS) total score. Secondary outcome measures included the Montgomery–Åsberg Depression Rating Scale (MADRS) total score, YMRS response (≥50% reduction in YMRS) and remission (YMRS score ≤12 at final visit) rates, and change from baseline to week 3 in Clinical Global Impression-Bipolar-Severity of Illness (CGI-BP-S) and CGI-BP-Change (CGI-BP-C) scores. Safety profile and tolerability evaluations included monitoring of adverse events, clinical laboratory values, vital signs, extrapyramidal symptoms (including akathisia), and electrocardiogram results. Results Compared with placebo (n = 159), quetiapine XR monotherapy (n = 149; mean daily dose, 604 mg) significantly improved manic symptoms starting at day 4 (first assessment; P < 0.001), with sustained improvement to study end (week 3; P < 0.001). MADRS scores showed greater improvement from baseline to study end with quetiapine XR than with placebo ( P = 0.004). Response and remission rates were significantly greater ( P < 0.01) with quetiapine XR than with placebo at study end. Quetiapine XR also resulted in significant improvements over placebo in CGI-BP-S and CGI-BP-C scores ( P < 0.001 and P < 0.001, respectively). Adverse events were mild to moderate in intensity; the most common ones associated with quetiapine XR were sedation, dry mouth, and somnolence. Conclusion This 3-week trial suggests that quetiapine XR (400–800 mg) once-daily monotherapy is efficacious (from day 4) and generally well tolerated in patients with manic or mixed episodes of bipolar I disorder. ClinicalTrials.gov identifier: NCT00422123.

PMH71 The Impact of Once-Daily Extended-Release Quetiapine Fumarate (Quetiapine XR) on Length and Costs of Hospitalisation of Patients with Schizophrenia or Bipolar Disorder

PMH71 The Impact of Once-Daily Extended-Release Quetiapine Fumarate (Quetiapine XR) on Length and Costs of Hospitalisation of Patients with Schizophrenia or Bipolar Disorder

PMH72 The Impact of Once-Daily Extended-Release Quetiapine Fumarate (Quetiapine XR) on Length of Hospitalisation of Patients with Acute Bipolar Mania

THE IMPACT OF ONCE-DAILY EXTENDED-RELEASE QUETIAPINE FUMARATE (QUETIAPINE XR) ON LENGTH OF HOSPITALISATION OF PATIENTS WITH ACUTE BIPOLAR MANIA Bonafede M1, Locklear JC2, Wahlqvist P3, Fajutrao L4, Szamosi J4, Pan K5, Eriksson H4 1Thomson Reuters, Andover, MA, USA, 2AstraZeneca Pharmaceuticals LP, Wilmington, DE, USA, 3AstraZeneca, Molndal, Sweden, 4AstraZeneca, Sodertalje, Sweden, 5Thomson Reuters, Cambridge, MA, USA OBJECTIVES: Rapid titration schedule of extended-release quetiapine fumarate (quetiapine XR) for acute bipolar mania means an effective dose can be reached by Day 2 (versus Day 5 with quetiapine immediate release [IR]). This study evaluates the impact of quetiapine XR on length of hospitalisation in patients with acute bipolar mania, compared with quetiapine IR, using Thomson Reuters MarketScan® Hospital Drug Database data. METHODS: Inpatient discharges with an ICD-9 diagnosis of acute bipolar mania (296.0x, 296.1x, 296.4x or 296.6x), receiving quetiapine XR or IR, were identified. The impact of the XR formulation on length of hospitalisation was assessed using a generalised linear model, adjusting for patient and hospital characteristics. Length of hospitalisation data were not normally distributed, therefore log-transformed data were included. A post hoc sensitivity analysis evaluated length of hospitalisation (excluding an outlier quetiapine XR patient, with a length of stay 3x higher than the second longest). RESULTS: In total, 3088 discharges between July 1, 2007 and August 31, 2010 were analysed. Modelled results showed that treatment with quetiapine XR reduced the length of hospitalisation by 6.7% compared with IR (p50.11), which corresponds to 0.6 fewer days in hospital (6.7% of 9.6 days), based on least squares mean estimations of length of hospitalisation in patients treated with quetiapine IR. With the outlier excluded, quetiapine XR significantly reduced the length of hospitalisation by 9.6% compared with IR (p50.02), corresponding to 0.9 days (9.6% of 9.6 days). CONCLUSIONS: Inpatient use of quetiapine XR in patients with acute bipolar mania may be associated with reduced length of hospitalisation, possibly due to the faster titration schedule for quetiapine XR versus IR. Given the high costs associated with hospitalisation, a reduction in length of stay of approximately 7 to 10% could represent a non-trivial cost reduction and potential savings.

A Randomized, Double-Blind Study of Once-Daily Extended Release Quetiapine Fumarate (Quetiapine XR) Monotherapy in Patients With Generalized Anxiety Disorder

This study evaluated once-daily, extended-release quetiapine fumarate (quetiapine XR) monotherapy in generalized anxiety disorder (GAD). This was a 10-week (8-week active treatment/2-week posttreatment drug-discontinuation/tapering phase), double-blind, randomized, placebo-controlled study (D1448C00009). Primary end point was change from randomization at week 8 in Hamilton Anxiety Rating Scale (HAM-A) total score. Overall, 951 patients with GAD were randomized (quetiapine XR: 50 mg/d, n = 234; 150 mg/d, n = 241; 300 mg/d, n = 241; placebo, n = 235). At week 8, HAM-A total scores significantly (P < 0.001) improved versus placebo (-11.10) with quetiapine XR 50 mg/d (-13.31) and 150 mg/d (-13.54), but not 300 mg/d (-11.87; P = 0.240). At week 1, HAM-A total scores significantly improved versus placebo (-5.94) with quetiapine XR 50 mg/d (-7.47; P < 0.01), 150 mg/d (-8.19; P < 0.001), and 300 mg/d (-7.23; P < 0.01). Versus placebo at week 8, quetiapine XR 50 and 150 mg/d significantly improved HAM-A psychic (P < 0.01 and P < 0.001, respectively) and somatic (P < 0.001; P < 0.01, respectively) cluster scores, HAM-A response (≥ 50% total score reduction; P < 0.05), and Clinical Global Impression-Improvement categorical changes (P < 0.05). For quetiapine XR 150 mg/d, significant (P < 0.05) improvements were seen for HAM-A remission (total score, ≤ 7) and Clinical Global Impression-Severity of Illness scores. For quetiapine XR 300 mg/d, improvements in these secondary variables were not significantly different versus placebo. Pittsburgh Sleep Quality Index global scores improved with all 3 doses (quetiapine: XR 50 mg/d, -4.07 [P < 0.05]; 150 mg/d, -4.38 [P < 0.05]; 300 mg/d, -3.97 [P < 0.05], versus -3.31 with placebo). Adverse events (>10% with quetiapine XR) were dry mouth, somnolence, sedation, dizziness, headache, and fatigue. Quetiapine XR (50/150 mg/d) monotherapy was effective at week 8 in patients with GAD; symptom improvement was seen at week 1 for all doses (50/150/300 mg/d). Safety and tolerability were consistent with the known profile of quetiapine.

P03-242 - Efficacy and tolerability of quetiapine XR 400/600/800mg/day in acute schizophrenia: a post-hoc analysis of data from two pooled randomised studies

IntroductionData from two, identically designed, placebo-controlled, randomised, double-blind clinical trials (D1444C00132+D1444C00133) for once-daily extended-release quetiapine fumarate (QTP-XR) were pooled and analysed.ObjectiveEvaluate dose response, efficacy and safety for QTP-XR in schizophrenia.MethodsPost-hoc analysis of data from patients receiving QTP-XR 400, 600, 800 mg/day or placebo. Endpoints: least squares means (LSM) change from baseline to Day 42 in PANSS total and positive and negative subscale scores. No corrections for multiplicity were performed. Adverse events (AEs) were recorded.Results914 patients were included; PANSS scores were assessed in the MITT population (n = 889). LSM change from baseline in PANSS total score diverged significantly from placebo at: Day 14 for QTP-XR 800 mg/day (-15.3 vs -12.1 for placebo; p = 0.018); Day 21 for 600 mg/day (-17.3 vs -14.2; p = 0.039); Day 42 for 400 mg/day (-19.2 vs -15.4; p = 0.033).Jonckheere-Terpstra analysis of change in PANSS total score at Day 42 showed a significant QTP-XR dose response (p = 0.0196; p &lt; 0.001 with placebo). PANSS positive scores diverged by Day 21 for both QTP-XR 800 (-5.7 vs -4.8; p = 0.049) and 600 mg/day (-5.8 vs -4.8; p = 0.046). PANSS negative scores diverged by Day 21 (-4.0 vs -3.2; p = 0.040) and 42 (-4.8 vs -3.6; p = 0.009) for QTP-XR 800 and 600 mg/day, respectively. AEs occurred in 59.4%, 66.5%, 62.1% and 56.2% of patients in the QTP-XR 800, 600, 400 mg/day and placebo groups, respectively. Most common AEs were somnolence, dry mouth, sedation, insomnia, dizziness, headache, constipation and nausea.ConclusionsQTP-XR was generally well tolerated and demonstrated efficacy that increased with dose in schizophrenia.Financial support: AstraZeneca.

Safety and tolerability of once‐daily extended release quetiapine fumarate in acute schizophrenia: pooled data from randomised, double‐blind, placebo‐controlled studies

Extended release quetiapine fumarate (quetiapine XR) is a new formulation that allows once-daily dosing and a titration regimen that is simpler than that of immediate release quetiapine (quetiapine IR) and may potentially increase patients' adherence to their prescribed medication. The tolerability of quetiapine XR was examined in an analysis of pooled data from three Phase III, double-blind, placebo-controlled, randomised studies with quetiapine IR as a reference treatment. The overall incidence of adverse events (AEs) was similar for quetiapine XR (69.5%) and quetiapine IR (72.5%). Most AEs were mild to moderate in severity and in line with those observed with quetiapine IR. The more rapid dose titration of quetiapine XR did not produce any new safety concerns and was as well tolerated as the regimen for quetiapine IR. The results of this pooled analysis show that quetiapine XR administered once daily is generally as well tolerated as quetiapine IR given twice daily. These data, together with the simpler dose-titration of quetiapine XR that allowed therapeutically effective doses to be reached by Day 2, suggest that this formulation potentially may improve adherence in patients with schizophrenia.

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

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<0.01). Quetiapine XR 300 mg/d showed significant improvements vs. placebo for: MADRS total score from week 1 onwards; MADRS response [(> or = 50% total score reduction) 58.9% vs. 46.2%, p<0.05] and remission [(total score < or = 8) 42.5% vs. 24.5%, p<0.01] rates; Hamilton Depression Rating Scale (HAMD) (-13.53 vs. -10.80, p<0.01) and Clinical Global Impression-Severity of illness (CGI-S) change (-1.52 vs. -1.23, p<0.05) at week 6. For quetiapine XR 150 mg/d, improvements were not significantly different vs. placebo, except for MADRS (weeks 1 and 2) and HAMD (week 6) total scores. Withdrawal rates due to adverse events (AEs) were: quetiapine XR 150 mg/d 11.5%, 300 mg/d 19.5%, and placebo 0.7%. The most common AEs (>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.

PW01-03 - Evaluation of the effects of quetiapine XR monotherapy on sleep disturbance in patients with MDD

ObjectivesEvaluate the effects of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy on sleep disturbance in patients with major depressive disorder (MDD).MethodsPooled data from four 6- or 8-week placebo-controlled quetiapine XR (50-300mg/day, administered in the evening) monotherapy studies (D1448C00001, D1448C00002, D1448C00003, D1448C00004) were analysed. Primary endpoint: change from randomisation in Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Post-hoc analyses assessed changes in: MADRS item 4 (reduced sleep); Hamilton Rating Scale for Depression (HAM-D) items 4 (insomnia-early), 5 (insomnia-middle) and 6 (insomnia-late) and sleep disturbance factor (items 4+5+6); Pittsburgh Sleep Quality Index (PSQI) total and item scores. MADRS total score change was analysed for patients experiencing high (baseline HAM-D sleep disturbance factor score &gt;=4) and low (baseline HAM-D sleep disturbance factor score &lt; 4) sleep disturbance.ResultsIn total, 2,116 patients were randomised. At last assessment, quetiapine XR (all doses combined) significantly (p&lt; 0.001) reduced MADRS item 4, HAM-D sleep disturbance factor and items 4, 5 and 6 and PSQI total scores from baseline versus placebo. Quetiapine XR significantly (p&lt; 0.001) improved MADRS total score from baseline versus placebo at all time points in patients experiencing high sleep disturbance (n=865, quetiapine XR; n=514, placebo). Quetiapine XR improved MADRS total score versus placebo in patients with low sleep disturbance (n=252, quetiapine; n=121, placebo): difference significant at Weeks 2(p&lt; 0.001), 4(p&lt; 0.05) and 6(p&lt; 0.05).ConclusionsQuetiapine XR monotherapy improved symptoms of sleep disturbance in MDD and was effective against depressive symptoms in patients experiencing high and low sleep disturbance levels. AstraZeneca funded.

PW01-24 - Evaluation of the effects of quetiapine XR monotherapy according to MDD severity: pooled data from 4 placebo-controlled trials

ObjectivesEvaluate the effects of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in patients with major depressive disorder (MDD) according to disease severity.MethodsPooled data (quetiapine XR 50, 150 and 300mg/day doses combined) from four 6- or 8-week placebo-controlled quetiapine XR monotherapy studies (D1448C00001, D1448C00002, D1448C00003, D1448C00004) were analysed. Key inclusion criterion for all 4 studies: HAM-D total score ≥22. Primary endpoint: change from randomisation in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. A post-hoc analysis assessed change from randomisation in MADRS total score and MADRS response (≥ 50% reduction in MADRS total score) at endpoint (Week 6 or Week 8) in 6 severity cohorts (defined by a MADRS total score at randomisation ≥24, ≥26, ≥28, ≥30, ≥32 or ≥34).Results1752 patients (comprising the l’ all patients’ group) were evaluated (MADRS score ≥24 at randomisation, n=1601; ≥26, n=1467; ≥28, n=1269; ≥30, n=1038; ≥32, n=745; ≥34, n=500). Quetiapine XR significantly reduced mean MADRS total score at endpoint in lrsquo;all patients’ (p&lt; 0.001 vs placebo) and in all 6 severity cohorts (≥24, ≥26, ≥28, ≥30 and ≥32, p&lt; 0.001 vs placebo; ≥34, p&lt; 0.01 vs placebo). MADRS response rates were significantly higher in the quetiapine XR group vs placebo in the ‘all patients’ group (p&lt; 0.001 vs placebo) and in all 6 severity cohorts (≥24, ≥26, ≥28, ≥30 and ≥32, p&lt; 0.001 vs placebo; ≥34, p=0.001 vs placebo).ConclusionsQuetiapine XR monotherapy significantly improved depressive symptoms in patients with MDD irrespective of disease severity, including the most severe levels of depression.AstraZeneca funded