Quetiapine XR Group Research Articles

Change in daytime sleepiness and cognitive function in a 6-month, double-blind study of lurasidone and quetiapine XR in patients with schizophrenia

Daytime sleepiness is a commonly reported adverse effect associated with psychotropic agents that may impair cognitive performance and functioning. The objective of this post-hoc analysis was to evaluate the long-term effects of lurasidone and quetiapine XR on daytime sleepiness and neurocognitive performance during a 6-month, double-blind continuation study, in subjects who completed an initial 6-week, randomized, placebo-controlled trial comparing these agents. Daytime sleepiness, cognitive performance, and health-related quality of life were assessed with the Epworth Sleepiness Scale (ESS), CogState computerized battery, and the Quality of Well-Being (QWB-SA) Scale, respectively. Treatment with flexible-dose lurasidone 40–160mg/d, administered once daily in the evening, was associated with significantly reduced daytime sleepiness compared with flexibly dosed quetiapine XR 200–800mg/d (p=0.03, effect size=0.36) at week 32 (month 6 of the continuation study endpoint). Incidence of markedly high sleepiness (ESS >10) was significantly higher in the quetiapine XR (200–800mg/d) group compared with the lurasidone (40–160mg/day) group at both months 3 and 6 visits (p<0.05). Lurasidone (40–160mg/d) significantly improved neurocognitive performance compared to quetiapine XR (200–800mg/d) before (effect size=0.49) and after adjustment (effect size=0.45) for sleepiness effect (p=0.008 and 0.010, respectively). Increased daytime sleepiness was significantly associated with reduced neurocognitive performance (p=0.019) and quality of well-being (p=0.05). Our findings suggest that clinicians should actively monitor patients for the presence of daytime sleepiness due in part to its potential impact on neurocognitive performance and well-being.

Weight change during long-term treatment with lurasidone: pooled analysis of studies in patients with schizophrenia.

The objective of this analysis was to evaluate the effect of 12 months of treatment with lurasidone on weight in patients with schizophrenia. Post-hoc, observed-case analysis included pooled data from six studies on 40–160 mg/day lurasidone; two studies included active comparators (2–6 mg/day risperidone or 200–800 mg/day quetiapine XR). Overall, 593 patients completed 12 months of treatment (N=471 lurasidone, N=89 risperidone, N=33 quetiapine XR). The mean baseline weight was 72.8, 80.8, and 72.4 kg in the lurasidone, risperidone, and quetiapine XR groups, respectively. The mean weight change at month 12 was −0.4 kg with lurasidone, +2.6 kg with risperidone, and +1.2 kg with quetiapine XR. Weight gain of at least 7% from study baseline was observed in 16.0, 25.8, and 15.2% of patients, and weight loss of at least 7% was seen in 18.5, 6.7, and 9.1% of patients treated with lurasidone, risperidone, and quetiapine XR, respectively. A shift from normal/underweight baseline BMI status to overweight/obese at month 12 occurred in 10.2, 27.6, and 15.0% of patients in the lurasidone, risperidone, and quetiapine XR groups, respectively. Conversely, 14.3, 1.7, and 7.7% of patients, respectively, shifted from overweight/obese to normal/underweight. In summary, a low potential for clinically significant weight gain was observed in patients with schizophrenia treated continuously with lurasidone for 12 months.

Long-term Lurasidone Treatment is Not Associated with Clinically Significant Elevations of Prolactin- or Hyperprolactinaemia-related Adverse Events: a Post-HOC Analysis

Introduction Elevation of prolactin level is a known adverse effect of antipsychotics. Long-standing hyperprolactinaemia may inhibit reproductive function by impairing gonadal steroidogenesis and is associated with a number of adverse effects such as galactorrhoea, amenorrhoea, gynecomastia, impotence and decreased bone mineral density. Lurasidone is a recently approved atypical antipsychotic agent for the treatment of schizophrenia. Aims/Objectives To compare the incidence of treatment-emergent adverse events (TEAEs) related to hyperprolactinaemia in patients treated with lurasidone or active comparators. Methods Pooled data from two 52-week studies that evaluated the long-term safety and efficacy of lurasidone compared with quetiapine XR or risperidone in patients with schizophrenia were reviewed post-hoc for prolactin levels and TEAEs considered to be related to hyperprolactinaemia. Results Prolactin levels decreased marginally in the lurasidone group (median -8.00 pmol/L, N=624) and quetiapine XR group (median -17.39 pmol/L, N=85), and increased in the risperidone group (median 385.00 pmol/L, N=199) (LOCF). The incidence of markedly abnormally high prolactin values (≥5× upper limit of normal) was 2.0%, 1.4% and 4.0% in the three groups, respectively. The hyperprolactinaemia-related TEAEs breast mass, gynecomastia, breast enlargement, breast tenderness, hypogonadism, infertility, pituitary tumors and mammary gland tumors were absent from all groups. Low rates (≤2.5%) of galactorrhoea, amenorrhoea and erectile dysfunction were seen in the lurasidone and risperidone groups, while no TEAEs were recorded in the quetiapine XR group. Conclusions This post-hoc review shows that long-term treatment with lurasidone was not associated with a clinically significant increase in prolactin levels and the incidence of associated TEAEs was low.

Efficacy and safety of extended-release quetiapine fumarate in youth with bipolar depression: an 8 week, double-blind, placebo-controlled trial.

Quetiapine is an atypical antipsychotic with demonstrated efficacy in the treatment of adolescent schizophrenia and pediatric bipolar mania. Large, placebo-controlled studies of interventions in pediatric bipolar depression are lacking. The current study investigated the efficacy and safety of quetiapine extended-release (XR) in patients 10-17 years of age, with acute bipolar depression. This multicenter, double-blind, randomized, placebo-controlled study investigated quetiapine XR (dose range, 150-300 mg/day) in pediatric outpatients with an American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) diagnosis of bipolar I or bipolar II disorder (current or most recent episode depressed) treated for up to 8 weeks (ClinicalTrials.gov identifier: NCT00811473). The primary study outcome was mean change in Children's Depression Rating Scale-Revised (CDRS-R) total score. Secondary efficacy outcomes included CDRS-R-based response and remission rates. Of 193 patients randomized to treatment, 144 patients completed the study (75.3% of quetiapine XR group [n=70]; 74.0% of placebo group [n=74]). Least squares mean changes in CDRS-R total score at week 8 were: -29.6 (SE, 1.65) with quetiapine XR and -27.3 (SE, 1.60) with placebo, a between-treatment group difference of -2.29 (SE, 1.99; 95% CI, -6.22, 1.65; p=0.25; mixed-model for repeated measures analysis). Rates of response and remission did not differ significantly between treatment groups. The safety profile of quetiapine XR was broadly consistent with the profile reported previously in adult studies of quetiapine XR and pediatric studies of quetiapine immediate-release (IR). Potentially clinically significant elevations in clinical chemistry values included triglycerides (9.3%, quetiapine XR; 1.4%, placebo group) and thyroid stimulating hormone (4.7%, quetiapine XR; 0%, placebo group). An adverse event potentially related to diabetes mellitus occurred in 3.3% of the quetiapine XR versus no adverse events in the placebo group. Quetiapine XR did not demonstrate efficacy relative to placebo in this 8 week study of pediatric bipolar depression. Quetiapine XR was generally safe and well tolerated.

Quetiapine Fumarate Extended‐Release for the Treatment of Major Depression With Comorbid Fibromyalgia Syndrome: A Double‐Blind, Randomized, Placebo‐Controlled Study

Fibromyalgia and major depressive disorder (MDD) frequently co-occur. Quetiapine fumarate extended-release (quetiapine XR) has demonstrated efficacy in the treatment of MDD and has been shown to have analgesic properties in patients with depression. The primary objectives of this study were to evaluate the effects of quetiapine XR on depressive and pain symptoms in patients with MDD and comorbid fibromyalgia, and to assess its safety and tolerability. This was an 8-week, single-center, double-blind, randomized, controlled trial. A total of 120 nonpsychotic adult outpatients who fulfilled the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnostic criteria for MDD and whose diagnosis of fibromyalgia was confirmed according to the American College of Rheumatology criteria were enrolled. The primary end point was the mean change from baseline to week 8 on the 17-item Hamilton Depression Rating (HAM-D) scale. Secondary end points included other depression-rating scores, pain scores, fibromyalgia scores, measures of quality of life and global functioning, and adverse events. The mean change in the HAM-D score from baseline to week 8 was significantly greater in the quetiapine XR group compared with the placebo group (-10.0 versus -5.8; P = 0.001). Improvements in most secondary outcomes were also significantly greater in the quetiapine XR group. Quetiapine XR was generally well tolerated. This study is the first to demonstrate that measures of depression, pain, and quality of life are significantly improved with quetiapine XR compared with placebo in patients with a dual diagnosis of MDD and fibromyalgia.

Quetiapine extended-release (Seroquel-XR) versus amitriptyline monotherapy for treating patients with fibromyalgia: a 16-week, randomized, flexible-dose, open-label trial

Previous open-label studies have suggested that quetiapine could be a valuable alternative for treating fibromyalgia. This study aims to compare the efficacy and tolerability of extended-release quetiapine with amitriptyline for treating fibromyalgia. This study was a randomized, open-label, flexible-dose, non-inferiority trial. Patients with fibromyalgia were randomized to receive quetiapine extended-release (XR) (N = 45) (50 to 300 mg daily) or amitriptyline (N = 45) (10 to 75 mg daily) for 16 weeks. The primary endpoint was the change from baseline to endpoint in the Fibromyalgia Impact Questionnaire (FIQ) total score; the non-inferiority threshold was established at 8 points. The secondary outcomes included sleep quality, anxiety, depression, and quality of life. Twenty-two (49%) patients in the quetiapine group and 34 (76%) patients in the amitriptyline group completed the study. We found a reduction of 9.8 points in the total FIQ score at the endpoint for the quetiapine-treated patients compared to 13.9 points for the amitriptyline-treated patients, for a difference of 4.14 points (80% confidence interval (CI) -0.70 to 8.98). No significant differences were found between the quetiapine XR and amitriptyline groups for any of the secondary outcomes. The proportion of patients discontinuing treatment due to adverse events was higher in the quetiapine group (n = 14, 31.1%) than the amitriptyline group (n = 3, 6.6%). Our results appear to indicate that quetiapine XR does not provide similar efficacy to amitriptyline for treating patients with fibromyalgia. Quetiapine XR had a worse tolerability than amitriptyline in this population, possibly due to a relatively high starting dose.

Effect of quetiapine XR on depressive symptoms and sleep quality compared with lithium in patients with bipolar depression

BackgroundBipolar depression is one of the most serious psychiatric conditions. In addition, sleep disturbance in bipolar disorder is common, and therapeutic agents restoring sleep disturbances in bipolar disorder patients will be clinically beneficial. In the current study, we compared the effect of quetiapine XR with lithium on depressive symptoms and sleep in bipolar depression patients during 8 weeks of trial. MethodsAn open-label, randomized comparison of sleep-activity and depressive symptoms between 8-week quetiapine XR monotherapy and lithium monotherapy for bipolar depression was conducted. Each assessment consisted of HDRS-17, Clinical Global Impression-severity (CGI-S), and self-reported Pittsburgh Sleep Quality Index (PSQI). Actigraphy-measured sleep parameters were assessed. ResultsA total of 42 patients (35.7±10.9 years; gender: male 15, female 27) with bipolar depression were screened out. Out of 42 patients, six patients were excluded before randomization. After randomization, seven patients were withdrawn. Twenty-nine patients with more than two visits after randomization (lithium group: 17, quetiapine XR group: 12, mean age: 36.1±10.4, gender: male 13, female 16) were included in the final analysis. In both groups, Hamilton Depression Rating Scale (HDRS) scores were significantly decreased at weeks 1, 2, 4, 6, and 8 compared with baseline. Remission rate (HDRS≤7) in the quetiapine XR was significantly higher than that of the lithium group. In the quetiapine XR group, PSQI scores at weeks 1, 2, 4, 6, and 8 was significantly decreased compared with baseline. Sleep efficiency at weeks 6 and 8 was significantly increased. WASO at week 8 was significantly decreased. LimitationsFirst, the present study was conducted with the relatively small number of study subjects. Second, bias could have affected the study results due to its open-label design. Third, study subjects were made up of high proportion of bipolar II disorder patients. ConclusionsQuetiapine XR monotherapy was more effective in treating bipolar depression than lithium. In particular, quetiapine XR treatment improved both subjective and objective sleep quality in patients with bipolar depression. However, relationship between favorable sleep quality and depressive symptom improvement were limited.

EPA-0419 – Effect of 12 months of treatment on weight in subjects with schizophrenia: a comparison of lurasidone, risperidone, and quetiapine XR

Introduction The prevalence of obesity and associated cardiometabolic comorbidity is significantly higher among patients diagnosed with schizophrenia compared to the general population (Mitchell et al. Schizophr Bull 2013;39:306-18) Objectives To evaluate the effect of 12 months of treatment with lurasidone, risperidone, or quetiapine XR (QXR) on weight and body mass index (BMI) in subjects with schizophrenia. Methods A post-hoc, observed case (OC) analysis was performed on pooled data from 6 clinical studies that evaluated the safety of 12 months of treatment with lurasidone (40–120 mg/day; n=471), risperidone (n=89), and QXR (n=33). Results The mean weight at baseline in the lurasidone, risperidone and QXR groups was 72.8, 80.8, and 72.4 kg; with 18.5%, 32.6%, and 15.2%, respectively, meeting standard BMI criteria for obesity. The mean change in weight (kg) in the lurasidone, risperidone and QXR groups, respectively, was −0.5, +1.7, and +1.5 at 3 months; −0.4, +2.2, and +1.5 at 6 months; and −0.4, +2.6, and +1.2 at 12 months. A clinically significant increase in weight (≥7%) occurred in the lurasidone, risperidone and QXR groups in 15.7%, 25.0%, and 15.2% of subjects, respectively, at 12 months; and a decrease of ≥7% in weight occurred in 18.6%, 6.8%, and 9.1% of subjects, respectively at 12 months. Similar changes in BMI were observed at 12 months. Conclusions The results of this pooled analysis of subjects with schizophrenia who completed 12 months of treatment suggest that lurasidone is associated with a low potential for clinically significant weight gain.

Treatment Patterns, HealthCare Resource Utilization and Costs in Patients with Bipolar Disorder, Newly Treated with Extended Release or Immediate Release Quetiapine Fumarate using US Healthcare Administrative Claims Data

BackgroundDifferences in treatment patterns, health care resource use, and costs are expected among patients newly treated with quetiapine extended release (XR) or quetiapine immediate release (IR). ObjectiveTo compare treatment patterns, health care resource use, and costs in patients with bipolar disorder newly treated with quetiapine XR or quetiapine IR. MethodsThis was an observational, retrospective cohort study that used HealthCore Integrated Research Database–identified patients (age range, 18-64 years) with an International Classification of Disease, Ninth Revision diagnosis of bipolar disorder and ≥1 pharmacy claim for quetiapine XR or quetiapine IR between October 2, 2008, and July 31, 2010. Outcomes were as follows: patient characteristics at the index date (first claim for quetiapine XR or quetiapine IR); 12-month preindex clinical characteristics, health care resource use, and costs; and 12-month postindex treatment patterns, health care resource use, and costs, assessed using generalized linear models (adjusted for index date and preindex patient demographic characteristics, clinical characteristics, health care resource use, and costs). ResultsIn total, 3049 patients with bipolar disorder were analyzed (651 in the quetiapine XR group and 2398 in the quetiapine IR group). Of patients initiating treatment with quetiapine XR, 8.8% had no change in or discontinuation of their index therapy compared with 5.7% of patients treated with quetiapine IR (adjusted odds ratio, 1.44; 95% confidence interval, 1.03-2.00; P = 0.0317). The average daily dose (adjusted mean) of quetiapine XR was higher than quetiapine IR (225 vs 175 mg/d, P < 0.0001). An average daily dose of 300 to 800 mg was reached sooner (15.6 vs 30.8 days, P = 0.0049) and in more patients (44.2% vs 27.2%, P < 0.0001) who were taking quetiapine XR compared with patients taking quetiapine IR. No differences in total health care costs were found between the cohorts; however, patients taking quetiapine XR were less likely to be hospitalized for mental health–related reasons (12.1% vs 18.3%, P = 0.0022) and incurred lower mental health–related costs (US $6686 vs US $7577, P = 0.0063) compared with patients taking quetiapine IR. ConclusionsTreatment patterns and dosing differ in patients with bipolar disorder treated with quetiapine XR compared with those treated with quetiapine IR. Mental health–related hospitalizations and costs may be reduced in the 12 months after patients initiating treatment with quetiapine XR compared with initiating treatment with quetiapine IR.

Effect of lurasidone on neurocognitive performance in patients with schizophrenia: A short-term placebo- and active-controlled study followed by a 6-month double-blind extension

This double-blind study evaluated change in cognitive performance and functional capacity in lurasidone and quetiapine XR-treated schizophrenia patients over a 6-week, placebo-controlled study, followed by a 6-month, double-blind extension. Cognitive performance and functional capacity were assessed with the CogState computerized cognitive battery and the UPSA-B. Analyses were conducted for all subjects, as well as the subsample whose test scores met prespecified validity criteria. No statistically significant differences were found for change in the composite neurocognitive score for lurasidone (80mg/day and 160mg/day) groups, quetiapine XR and placebo in the full sample at week 6. For the evaluable sample (N=267), lurasidone 160mg was superior to both placebo and quetiapine on the neurocognitive composite, while lurasidone 80mg, quetiapine XR, and placebo did not differ. UPSA-B scores were superior to placebo at 6 weeks for all treatments. In the double-blind extension study, analysis of the full sample showed significantly better cognitive performance in the lurasidone (40–160mg) group compared to the quetiapine XR (200–800mg) group at both 3 and 6 months. Cognitive and UPSA-B total scores were significantly correlated at baseline and for change over time. This is the first study to date where the investigational treatment was superior to placebo on both cognitive assessments and a functional coprimary measure at 6 weeks, as well as demonstrated superiority to an active comparator on cognitive assessments at 6 weeks and at 6 months of extension study treatment. These findings require replication, but are not due to practice effects, because of the placebo and active controls.

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.

Effectiveness of lurasidone vs. quetiapine XR for relapse prevention in schizophrenia: A 12-month, double-blind, noninferiority study

ObjectiveTo evaluate the relapse prevention efficacy of lurasidone compared with quetiapine XR (QXR) in adults patients with schizophrenia. MethodThis double-blind study evaluated the relapse prevention efficacy of 12months of flexible-dose treatment with lurasidone (40–160mg/day) compared with QXR (200–800mg/day), in outpatients with an acute exacerbation of chronic schizophrenia who had recently completed a 6-week placebo-controlled trial of treatment with either lurasidone or QXR. The primary endpoint, time-to-relapse, was analyzed using a Cox proportional hazards model in this noninferiority trial. ResultsThe Kaplan–Meier estimate of the probability of relapse over 12months was 23.7% for subjects receiving lurasidone vs. 33.6% for QXR. The hazard ratio [95% CI] for probability of relapse was 0.728 [0.410, 1.295] (log-rank p=0.280). Since the upper limit of the hazard ratio (1.295) was smaller than the prespecified noninferiority margin (1.93), noninferiority of lurasidone compared with QXR was demonstrated in this study. The probability of hospitalization at 12months was lower for the lurasidone group compared with the QXR group (9.8% vs. 23.1%; log-rank p=0.049). A significantly higher proportion of lurasidone subjects achieved remission at study endpoint compared with the QXR group (61.9% vs. 46.3%; p=0.043). Discontinuation rates due to AEs were similar for lurasidone and QXR (7% vs. 5%). Treatment with lurasidone was not associated with clinically significant changes in weight or metabolic parameters. ConclusionsTwelve months of treatment with lurasidone met noninferiority criteria, and was associated with higher rates of remission, and reduced risk of hospitalization compared with QXR. No clinically significant effects on weight or metabolic parameters were observed during maintenance treatment with lurasidone.

Self-Reported Sedation Profile of Quetiapine Extended-Release and Quetiapine Immediate-Release During 6-Day Initial Dose Escalation in Bipolar Depression: A Multicenter, Randomized, Double-Blind, Phase IV Study

A human-volunteer study reported lower sedation intensity during escalation of the extended-release formulation of quetiapine fumarate (quetiapine XR) than the immediate-release (IR) formulation. To test the hypothesis that the profile of initial tolerability, including sedation, differs between the extended-release (XR) and immediate-release (IR) formulations of quetiapine in patients with bipolar depression. In a randomized, double-blind, double-dummy, parallel-group, Phase IV study, male and female inpatients aged 18 to 50 years with a Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) diagnosis of bipolar I or II depression were randomized after washout to receive placebo on day 1 and quetiapine XR or IR at escalating doses of 50, 100, 200, 300, and 300 mg once daily on the evenings of days 2 to 6, with hospital discharge on day 7. Sedation intensity was assessed by a self-reported modified Bond-Lader visual analog scale (VAS) score. Of 139 randomized patients, 134 completed the study. Mean patient age was 39.0 years; mean weight, 91.3 kg; and mean body mass index (calculated as weight in kilograms divided by height in meters squared), 31.0. Sedation intensity 1 hour after administration of the 50-mg dose (the primary study measure) was statistically significantly lower with quetiapine XR versus IR (mean [SD] VAS score: 33.4 [26.92] vs 44.0 [31.76]; least squares mean difference: 12.55, P = 0.009; modified intention-to-treat population). Sedation intensity was found in secondary analyses to be significantly lower with quetiapine XR than with quetiapine IR 1, 2, and 3 hours after each dose on days 2 to 6 (P ≤ 0.05), with similar sedation intensity between the treatment groups 4 to 14 hours postdose. Rates of treatment-related adverse events were 47.1% with quetiapine XR versus 59.4% with quetiapine IR. Three serious adverse events (4.3%) occurred in the quetiapine XR group. Adverse events led to study discontinuation in 1 patient (1.4%) in the quetiapine XR group and in 2 patients (2.9%) in the IR group. During the initial dose-escalation period studied, patients with bipolar depression reported statistically significantly lower sedation intensity in the 1 to 3 hours after taking quetiapine XR compared with the IR formulation. Overall tolerability for both formulations was consistent with the known profile of quetiapine. ClinicalTrials.gov identifier: NCT00926393.

P-201 - Effectiveness of quetiapine xr vs. sertraline in acute bipolar depression as add-on therapy to previous mood stabilizer treatment: a pilot study

Even at therapeutic doses, mood stabilizers do not completely address symptoms in bipolar depression. Some guidelines recommend add-on antidepressant therapy or quetiapine. Early effectiveness of quetiapine extended release (quetiapine XR) vs. sertraline in adults with bipolar depression; treated with lithium or valproate at clinically therapeutic blood levels (change from baseline in the MADRS global score at week 2 (LOCF) endpoint). Others (secondary objectives) were measured at week 8. Prospective, open label, randomized study of 8 weeks follow-up (D1443L00058). 27 patients were randomized to quetiapine XR (14) or sertraline (13). Mean age was 46.07 years. 17 patients (62.96%) were male. 20 (74.07%) were diagnosed with bipolar disorder type I. Mean number of previous events were 9.74. Mean baseline MADRS score was 28.23 (SD 5.86) and 29.50 (SD 5.00) for sertraline and quetiapine XR groups, respectively (p = 0.59). Mean change in MADRS score (2 weeks from baseline) was: -6.62 (sertraline group) and -13.14 (quetiapine XR group) (p = 0.08). Final change from baseline was: -10.62 (sertraline) and -17.14 (quetiapine XR) (p = 0.1). Patients with at least one AE and one AE leading to study withdrawal were 12 and 3, respectively (quetiapine XR group); and 9 and 2, respectively (sertraline group). The most frequent AEs were somnolence, dry mouth (35.7%, 21.4%, respectively) (quetiapine XR group), and insomnia, diarrhea, dyspepsia (14.3% for each one) (sertraline group). Numeric differences (though not significant) in favour of quetiapine XR exist for the early effectiveness of quetiapine XR in bipolar depression. Sponsorship by AstraZeneca.

Tolerability of extended‐release quetiapine fumarate compared with immediate‐release quetiapine fumarate in older patients with Alzheimer's disease with symptoms of psychosis and/or agitation: a randomised, double‐blind, parallel‐group study

The objective of this study was to assess the safety and tolerability of extended-release quetiapine fumarate (quetiapine XR) compared with quetiapine immediate-release (quetiapine IR) in older patients with Alzheimer's disease with symptoms of psychosis and/or agitation. This was a 6-week, double-blind, double-dummy, randomised study. Of the 109 patients screened, 100 were randomised to receive quetiapine XR (n = 68) or quetiapine IR (n = 32), at doses of 50 and 25 mg/day, respectively. Treatment was escalated to 100 mg/day by Day 4. At Day 8, a flexible-dose (50-300 mg/day) period began when dose adjustment was made at the investigator's discretion. The primary variable was incidence and type of adverse events (AEs). Secondary variables included efficacy and other safety assessments. Mean daily doses were 143.6 and 142.0 mg in the quetiapine XR and quetiapine IR groups, respectively. Ninety patients completed the study; only one withdrew (in the quetiapine XR group) because of an AE. Laboratory evaluations identified severe neutropaenia (one patient), mild neutropaenia (three patients) and eosinophilia (five patients); however, these were not reported, as AEs and confounding factors, such as patient age, concomitant illness and medication, made it difficult to determine any relationship to quetiapine treatment. Numerical improvements from baseline were seen across both treatment groups in Neuropsychiatric Inventory frequency × severity total, Neuropsychiatric Inventory-Nursing Home version, Cohen-Mansfield Agitation Inventory, Clinical Global Impression-Severity of Illness and Clinical Global Impression-Improvement scores. Quetiapine XR dosed up to 300 mg/day was generally well tolerated, with a similar profile to that of quetiapine IR.

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

Effectiveness of the extended release formulation of quetiapine as monotherapy for the treatment of acute bipolar depression

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.

Self-reported sedation profile of immediate-release quetiapine fumarate compared with extended-release quetiapine fumarate during dose initiation: A randomized, double-blind, crossover study in healthy adult subjects

Objectives: The primary study objective was to assess the time course and intensity of sedation after administration of immediate-release (IR) and extended-release (XR) quetiapine fumarate in healthy subjects during dose initiation. The tolerability of the 2 formulations was also evaluated. Methods: This was a randomized, double-blind, double-dummy, 2-period crossover study in healthy adult (age 18–50 years) subjects. It employed the dose-initiation schedule used in studies of the 2 quetiapine formulations in patients with bipolar depression: 50 mg on day 1, 100 mg on day 2, 200 mg on day 3, and 300 mg on days 4 and 5. Doses were administered in the morning. The primary end point was the level of sedation 1 hour after dosing on day 1, as rated by subjects using a visual analog scale (VAS) ranging from 0 = alert to 100 = drowsy. Secondary VAS end points included sedation over a 14-hour period on day 1, and on days 2 through 5. Blood was drawn on day 5 of both periods for determination of plasma drug concentrations by a liquid chromatography method with tandem mass-spectrometric detection. Adverse events (AEs) were recorded throughout the study. Results: Sixty-three subjects were enrolled in the study, comprising the safety population. The perprotocol population consisted of 58 subjects (79.0% male, 21.0% female; 67.2% black, 24.1% white; mean age, 31.8 years; mean weight, 80.7 kg). One hour after dosing on day 1, sedation was significantly greater with quetiapine IR than with quetiapine XR (mean VAS score, 33.2 vs 11.3, respectively; P < 0.001). There were no significant differences in sedation between formulations at 7 hours after dosing (64.5 and 53.6), 8 hours after dosing (46.9 and 50.8), or 14 hours after dosing (both, 12.7). On day 1, numerically more subjects had a VAS score>75 (substantial sedation) 1 hour after dosing in the quetiapine IR group than in the quetiapine XR group (14 vs 4 subjects). On day 5, the mean (95% CI) quetiapine C max for the IR and XR formulations was 689.19 (605.83–784.02) and 381.70 (341.40–426.76) ng/mL; the mean was AUC 0–11 was 2835.89 (2517.92–3194.02) and 2515.21 (2281.76-–2772.55) ng · h/mL; and the median T max was 2.0 and 5.0 hours. The incidence of any AEs was 21.7% with quetiapine IR and 9.8% with quetiapine XR. Conclusion: In these healthy subjects, quetiapine XR was associated with a lower intensity of self-reported sedation compared with quetiapine IR. ClinicalTrials.gov Identifier: NCT00702676; Astra Zenecaclinicaltrials.com Identifier: D1443C00033.

P.2.109 A double-blind placebo-controlled trial of risperidone in autistic disorder

Bipolar depression is one of the most serious psychiatric conditions. In addition, sleep disturbance in bipolar disorder is common, and therapeutic agents restoring sleep disturbances in bipolar disorder patients will be clinically beneficial. In the current study, we compared the effect of quetiapine XR with lithium on depressive symptoms and sleep in bipolar depression patients during 8 weeks of trial.An open-label, randomized comparison of sleep-activity and depressive symptoms between 8-week quetiapine XR monotherapy and lithium monotherapy for bipolar depression was conducted. Each assessment consisted of HDRS-17, Clinical Global Impression-severity (CGI-S), and self-reported Pittsburgh Sleep Quality Index (PSQI). Actigraphy-measured sleep parameters were assessed.A total of 42 patients (35.7±10.9 years; gender: male 15, female 27) with bipolar depression were screened out. Out of 42 patients, six patients were excluded before randomization. After randomization, seven patients were withdrawn. Twenty-nine patients with more than two visits after randomization (lithium group: 17, quetiapine XR group: 12, mean age: 36.1±10.4, gender: male 13, female 16) were included in the final analysis. In both groups, Hamilton Depression Rating Scale (HDRS) scores were significantly decreased at weeks 1, 2, 4, 6, and 8 compared with baseline. Remission rate (HDRS≤7) in the quetiapine XR was significantly higher than that of the lithium group. In the quetiapine XR group, PSQI scores at weeks 1, 2, 4, 6, and 8 was significantly decreased compared with baseline. Sleep efficiency at weeks 6 and 8 was significantly increased. WASO at week 8 was significantly decreased.First, the present study was conducted with the relatively small number of study subjects. Second, bias could have affected the study results due to its open-label design. Third, study subjects were made up of high proportion of bipolar II disorder patients.Quetiapine XR monotherapy was more effective in treating bipolar depression than lithium. In particular, quetiapine XR treatment improved both subjective and objective sleep quality in patients with bipolar depression. However, relationship between favorable sleep quality and depressive symptom improvement were limited.