Long-term mood/antidepressant effects of quetiapine extended-release formulation: an open-label, non-controlled extension study in Japanese patients with bipolar depression.

BACKGROUND: In an 8-week, randomized, placebo-controlled, double-blind study, an extended-release formulation of quetiapine, quetiapine XR, demonstrated efficacy and safety in Japanese patients with bipolar depression. Bipolar disorder is a chronic disease requiring continuous treatment. METHODS: This was a long-term (52-week), open-label, non-controlled extension study to evaluate the long-term safety and efficacy of quetiapine XR in Japanese patients with bipolar depression who had previously completed the initial 8-week double-blind study. Efficacy was determined by the Montgomery-Åsberg Depression Rating Scale (MADRS), Hamilton Depression Scale 17-item (HAM-D17), and Clinical Global Impressions-Bipolar scale (CGI-BP). Safety evaluations included analysis of adverse events, clinical laboratory measures, vital signs, Drug-induced Extrapyramidal Symptoms Scale, Young Mania Rating Scale, and the Columbia Suicide Severity Rating Scale. RESULTS: The mean (SD) MADRS total score decreased from 30.9 (6.9) at baseline to 16.1 (10.6) at week 8, and eventually to 9.1 (8.7) at week 52. The sustained efficacy of quetiapine XR treatment was also shown using HAM-D17 total scores, CGI-BP-Severity and Change evaluations. The most common adverse events were somnolence, nasopharyngitis, and thirst. Long-term treatment with quetiapine XR caused no substantial changes in the safety profiles, including clinical laboratory parameters, and no new safety concerns were identified. CONCLUSIONS: The efficacy of quetiapine XR was sustained long-term and no new safety concerns were identified in Japanese patients with bipolar depression. TRIAL REGISTRATION: ClinicalTrials.gov Registration: NCT01725308. Date of registration; 12th November 2012 (retrospectively registered).

A controlled trial of quetiapine XR coadministration treatment of SSRI-resistant panic disorder.

BACKGROUND: Open-label quetiapine coadministration with SSRI therapy, in a diagnostically mixed sample of comorbid anxiety patients, offered additional anxiolytic benefit. Therefore, we designed the following controlled trial to confirm these findings in a comorbid, SSRI-resistant, panic disorder (PD) patient sample. METHODS: This was a single-site, double-blind, placebo-controlled (PLAC), randomized, parallel group (2 groups), 8-week, quetiapine extended release (XR) coadministration trial. SSRI resistance was determined either historically or prospectively. Patients were randomized if they remained moderately ill (CGI-S score ≥ 4). Change in the PDSS scale total score was the primary efficacy outcome measure. Responders were identified as those with a ≥50 % decrease from their baseline PDSS score. In the early weeks of therapy, XR was flexibly and gradually titrated from 50 to 400 mg/day. RESULTS: 43 patients were screened in total, and 26 of these were randomized and evaluable. 21 patients (78 % of the randomized group) completed the trial (10 XR; 11 PLAC). The endpoint quetiapine XR mean daily dose ± SD was 150 ± 106 mg. While, in the sample as a whole, there was improvement in PDSS scores across the 8-week trial (ANOVA main effect of time, F = 10.9, df 8,192, p < 0.0001), the treatment × time interaction effect was not statistically significant (F = 0.8, df 8,192, p = 0.61). There was no between-group difference in responder frequency at endpoint. CONCLUSIONS: This proof-of-concept RCT did not support the efficacy of this treatment strategy for SSRI-resistant PD. Quetiapine XR was generally well-tolerated. Important limitations were the small sample size, and the relatively low average dose of quetiapine XR used. ClinicalTrials.gov ID#: NCT00619892.

[The place of quetiapine extended release in the treatment of mental disorders]. / Miejsce kwetiapiny o przedluzonym uwalnianiu w terapii osób z zaburzeniami psychicznymi.

This article presents a summary of available data on the use of quetiapine extended release (QUE-XR). QUE-XR is an example of an atypical antipsychotic drug that can be used in a single dose, thereby simplifying the treatment regimen. From the therapeutic standpoint, this issue is of paramount importance, since approximately 50% of patients have adherence issues. Therefore, availability of the drug which is comfortable in administration can significantly improve treatment outcomes. Due to its antipsychotic, antidepressive, mood stabilizing and anxiolytic efficacy, QUE-XR seems to be a promising drug with potentially broad spectrum of indications (in patients with schizophrenia, bipolar disorder, major depression and some anxiety disorders - both in the acute phase of treatment, and the maintenance treatment). Notably, QUE-XR seems to ameliorate sleep disturbances, and it may also improve patients' quality of life (as suggested by some studies). Due to the simple dosing regimen of QUE-XR, conducting therapy with this drug may contribute to the improvement of compliance. Yet, the primary clinical criterion for selection of the type of formulation of quetiapine should be the individual preferences of the patient, and the knowledge and experience of the treating physician.

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

OBJECTIVES: 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). DESIGN: An 11-week (9-week randomized; 2-week posttreatment phase), double-blind, placebo-controlled, Phase III study (D1448C00014). SETTING: A total of 53 centers in Argentina, Estonia, Finland, Russia, Ukraine, and the United States. PARTICIPANTS: 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). INTERVENTION: Patients were randomized to quetiapine XR (n = 166; flexible-dosing 50-300 mg/day) or placebo (n = 172). MEASUREMENTS: Primary outcome was Montgomery Åsberg Depression Rating Scale (MADRS) total score change from randomization at Week 9. RESULTS: 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. CONCLUSION: 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.

Multi-center, randomized, double-blind, placebo-controlled study of quetiapine extended-release formulation in Japanese patients with bipolar depression.

RATIONALE: Quetiapine fumarate is an atypical antipsychotic indicated for various mental disorders, but it has not been studied in Japanese patients with bipolar depression. OBJECTIVES: To evaluate the efficacy and safety of quetiapine XR (extended release) in Japanese patients with bipolar depression. METHODS: In this multi-center, randomized, double-blind, placebo-controlled, fixed-dose study of 431 Japanese adults with bipolar I or II disorder, efficacy was determined by analyzing the mean change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Secondary end points included MADRS response and remission rates, Hamilton Depression Scale 17-Item (HAM-D17), and Clinical Global Impressions-Bipolar (CGI-BP) scale scores. Safety was determined by monitoring adverse events and clinical assessments. RESULTS: This study revealed a statistically significantly greater decrease in MADRS total score after 8 weeks of quetiapine XR 300 mg/day monotherapy compared with placebo (- 12.6 vs. - 10.1; p = 0.034). There were also improvements in MADRS response (44.1 vs. 35.6%) and remission (38.0 vs. 26.6%) rates as well as in HAM-D17 and CGI-BP scale scores compared with placebo. In the subgroup analysis of patients with bipolar I or II disorder, the adjusted mean changes in MADRS total score compared to placebo were - 2.3 and - 2.1, respectively. Adverse events occurred in 149 patients (83.2%) receiving quetiapine XR 300 mg/day and in 81 patients (45.8%) receiving placebo. The most common adverse events were somnolence and thirst, which is consistent with the previously reported safety profile. CONCLUSIONS: Once-daily monotherapy with quetiapine XR is an effective and well-tolerated treatment for bipolar depression in Japanese patients.

A 6-week, multicenter, double-blind, double-dummy, chlorpromazine-controlled non-inferiorityrandomized phase iiitrial to evaluate the efficacy and safety of quetiapine fumarate (SEROQUEL) extended-release (XR) in the treatment of patients with schizophrenia and acute episodes.

This study aimed to evaluate the efficacy and safety of quetiapine fumarate extended-release (XR) in the treatment of Chinese patients with acute schizophrenia. Multicenter, double-blind, double-dummy, active-controlled non-inferiority randomized study in Chinese patients (n = 388) with schizophrenia randomly assigned to quetiapine XR or chlorpromazine for 6 weeks. Primary outcome was the change from baseline in Positive and Negative Syndrome Scale (PANSS) total score at the end of treatment. Safety objectives included adverse event (AE) monitoring, laboratory test results, and electrocardiograms. Changes in PANSS total score were -33.4 for quetiapine XR and -35.9 for chlorpromazine (P > 0.05). Least squares mean changes were: positive subscale, -9.9 ± 0.53 and -11.1 ± 0.51; negative subscale, -5.9 ± 0.50 and -6.7 ± 0.48; general psychopathology subscale, -12.9 ± 0.74 and -13.9 ± 0.71; aggression and hostility cluster scores, -4.8 ± 0.33 and -5.4 ± 0.32; and depression cluster scores, -1.8 ± 0.18 and -1.7 ± 0.18, for quetiapine XR and chlorpromazine, respectively. For quetiapine XR, AEs were constipation, dizziness, insomnia, and agitation, and nine patients (4.6%) discontinued due to AEs. For chlorpromazine, AEs were extrapyramidal symptoms, constipation, insomnia, dizziness, and agitation, and 17 patients (8.9%) discontinued due to AEs; two patients reported serious AEs. Quetiapine XR monotherapy was not inferior to chlorpromazine for treating acute schizophrenia in Chinese patients and was well tolerated.

Insight and Treatment Outcomes in Schizophrenia: Post-hoc Analysis of a Long-term, Double-blind Study Comparing Lurasidone and Quetiapine XR.

Objective: The objective of this post-hoc analysis was to evaluate the effect of lurasidone and quetiapine extended-release (XR) on insight and judgment and assess the longitudinal relationships between improvement in insight and cognitive performance, functional capacity, quality of well-being, and depressive symptoms in patients with schizophrenia. Design: Clinically unstable patients with schizophrenia (N=488) were randomized to once-daily, fixed-dose treatment with lurasidone 80mg, lurasidone 160mg, quetiapine XR 600mg, or placebo, followed by a long-term, double-blind, flexible-dose continuation study involving these agents. Results: Significantly greater improvement in insight and judgment (assessed by the Positive and Negative Syndrome Scale G12 item) for the lurasidone and quetiapine XR groups, compared to the placebo group, was observed at Week 6. Over a subsequent six-month continuation period, the flexible dose lurasidone group showed significantly greater improvement in insight from acute phase baseline compared to the flexible-dose quetiapine XR group (QXR-QXR) (p=0.032). Improvement in insight was significantly correlated with improvement in cognition (p=0.014), functional capacity (p=0.006, UPSA-B), quality of well-being (p=0.033, QWB), and depressive symptoms (p=0.05, Montgomery-Åsberg Depression Rating Scale [MADRS] score) across treatment groups and study periods. Conclusion: In this post-hoc analysis, flexibly dosed lurasidone 40 to 160mg/d was found to be associated with significantly greater improvement in insight compared to flexibly dosed quetiapine XR 200 to 800mg/d over long-term treatment in patients with schizophrenia. Across treatment groups, improvement in insight and judgment was significantly associated with improvement in cognition, functional capacity, quality of well-being, and depressive symptoms over time.

Efficacy and safety of quetiapine extended release monotherapy in bipolar depression: a multi-center, randomized, double-blind, placebo-controlled trial.

RATIONALE: Quetiapine extended release (XR) has been used to treat various psychiatric disorders, including depressive episodes associated with bipolar I and II disorders. Quetiapine XR is the first approved drug in China for the treatment of bipolar disorder. OBJECTIVES: The study evaluated the efficacy and safety of short-term quetiapine XR monotherapy in the treatment of depressive episodes of bipolar I and II disorders. METHODS: This was an 8-week multi-center, randomized, double-blind, placebo-controlled, fixed-dose phase 3 study. The primary endpoint was the mean change of the Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Secondary endpoints included Clinical Global Impressions-Bipolar (CGI-BP) and remission rates. RESULTS: The study recruited 279 adult bipolar I or II patients currently experiencing depression from 11 Chinese provinces. Of these, 139 received quetiapine XR (300 mg/day) and 140 received placebo for 8 weeks. The mean change in the MADRS total score was significantly greater in the quetiapine XR group than in the placebo group (-19.00 ± 7.88 vs. -16.20 ± 9.32; p = 0.004). Adverse events occurred in 96 patients (65.3 %) in the quetiapine XR group and 72 (49.0 %) in the placebo group. The incidence of serious adverse events did not differ significantly between the groups (p = 0.247). CONCLUSIONS: This study, which is the first to evaluate 300 mg/day quetiapine XR monotherapy for depression in Chinese patients with bipolar disorders, found that this drug was superior to the placebo. Quetiapine XR was generally safe and well tolerated (ClinicalTrials.gov number, NCT01256177).

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 40-160 mg/d, administered once daily in the evening, was associated with significantly reduced daytime sleepiness compared with flexibly dosed quetiapine XR 200-800 mg/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 (200-800 mg/d) group compared with the lurasidone (40-160 mg/day) group at both months 3 and 6 visits (p < 0.05). Lurasidone (40-160 mg/d) significantly improved neurocognitive performance compared to quetiapine XR (200-800 mg/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.

A Randomized, Placebo-Controlled Pilot Study of Quetiapine-XR Monotherapy or Adjunctive Therapy to Antidepressant in Acute Major Depressive Disorder with Current Generalized Anxiety Disorder.

OBJECTIVES: To pilot efficacy and safety data of quetiapine-XR monotherapy or adjunctive therapy to antidepressant(s) in the acute treatment of MDD with current generalized anxiety disorder (GAD). METHODS: The Mini International Neuropsychiatric Interview was used to ascertain the diagnosis of DSM-IV Axis I disorders. Eligible patients were randomly assigned to quetiapine-XR or placebo for up to 8 weeks. Changes from baseline to endpoint in Hamilton Depression Rating Scale-17 items (HAMD-17), Hamilton Anxiety Rating Scale (HAM-A), Clinical Global Impression-Severity (CGI-S), Quick Inventory of Depression Symptomatology-16 items Self-Report (QIDS-16-SR) total scores, and other outcome measures were analyzed with the last observation carried forward strategy and/or mixed-effects modeling for repeated measures. RESULTS: Of the 34 patients screened, 23 patients were randomized to receive quetiapine-XR (n = 11) or placebo (n = 12), with 5 and 4 completing the study, respectively. The mean dose of quetiapine-XR was 154 ± 91 mg/d. The change from baseline to endpoint in the total scores of HAMD-17, HAM-A, QIDS-16-SR, and CGI-S were significant in the quetiapine-XR group, but only the change in HAM-A total score was significant in the placebo group. The differences in these changes between the two groups were only significant in CGI-S scores, with the rest of numerical larger in the quetiapine-XR group. The most common side effects from quetiapine-XR were dry mouth, somnolence/sedation, and fatigue. CONCLUSIONS: In this pilot study, quetiapine-XR was numerically superior to placebo in reducing depressive and anxiety symptoms in patients with MDD and current GAD. Large sample studies are warranted to support or refute these preliminary findings.

Cost-effectiveness of lurasidone vs quetiapine extended-release (XR) in patients with bipolar depression.

OBJECTIVE: Bipolar disorder imposes a high economic burden on patients and society. Lurasidone and quetiapine extended-release (XR) are atypical antipsychotic agents indicated for monotherapy treatment of bipolar depression. Lurasidone is also indicated as adjunctive therapy with lithium or valproate for depressive episodes associated with bipolar disorder. The objective of this analysis was to estimate the cost-effectiveness of lurasidone and quetiapine XR in patients with bipolar depression. METHODS: A cost-effectiveness model was developed to compare lurasidone to quetiapine XR. The model was based on a US third-party payer perspective over a 3-month time horizon. The effectiveness measure in the model was the percentage of patients achieving remission (Montgomery-Åsberg Depression Rating Scale [MADRS] total score ≤12 by weeks 6-8). The comparison of remission rates was made through an adjusted indirect treatment comparison of lurasidone and quetiapine XR pivotal trials using placebo as the common comparator. Resource utilization for remission vs no remission was estimated from published expert panel data, and resource costs were obtained from a retrospective database study of bipolar I depression patients. Drug costs were estimated using the mean dose from clinical trials and wholesale acquisition costs. RESULTS: Over the 3-month model time period, lurasidone and quetiapine XR patients, respectively, had similar mean numbers of emergency department visits (0.48 vs 0.50), inpatient days (2.1 vs 2.2), and office visits (9.3 vs 9.6). More lurasidone than quetiapine XR patients achieved remission (52.0% vs 43.2%) with slightly higher total costs ($4982 vs $4676), resulting in an incremental cost-effectiveness ratio of $3474 per remission. The probabilistic sensitivity analysis showed lurasidone had an 86% probability of being cost-effective compared to quetiapine XR at a willingness-to-pay threshold of $10,000 per remission. CONCLUSIONS: Lurasidone may be a cost-effective option when compared to quetiapine XR for the treatment of adults with bipolar depression.

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

AIMS: 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. PATIENTS & METHODS: Generalized linear model analyses were used, adjusting for patient and hospital characteristics. RESULTS: 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. CONCLUSION: 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.

Characteristics of bipolar disorder patients treated with immediate- and extended-release quetiapine in a real clinical setting: a longitudinal, cohort study of 1761 patients.

OBJECTIVES: The objective of this work was to study characteristics and clinical treatment patterns of bipolar disorder (BD) patients admitted to hospital and treated with quetiapine (immediate-release [IR] or extended-release [XR] formulations). METHODS: BD patients admitted to hospital and prescribed quetiapine IR were followed by linking two Swedish nationwide registries; the hospitalization and drug dispense registries [ClinicalTrials.gov identifier: NCT01455961]. The study period was from 1 January 2008, to end of 31 December 2011. Data was primarily analysed using descriptive methods. RESULTS: Quetiapine IR was used in 1761 patients of whom 1303 subsequently switched to XR (switch XR) and 458 remained on IR (continuous IR). At baseline, Switch XR patients were younger (-3.3 years), more frequently employed (+7.1%), had higher prevalence of single depressive episodes (+6.7%) and anxiety disorders (+5.8%), lower mean daily IR dose (-19.3%) and fewer medications for somatic disorders (-7.5%) than continuous IR patients. During follow up, the number of concomitant psychiatric medications was lower in switch XR patients (-6%) and higher in continuous IR patients (+6%). Mean daily quetiapine dose was 21% higher in switch XR versus continuous IR patients. Prescriptions of lower quetiapine dosages calculated below 50 mg per day in the XR switch and IR continuous groups were seen in 8% versus 10% of the patients, respectively. CONCLUSIONS: Differential use of quetiapine XR and IR in bipolar disorder patients with different and important characteristics was demonstrated. Patients who were switched to quetiapine XR had a higher psychiatric disease burden, were younger and had a higher degree of employment. These differences demonstrate the heterogeneity among bipolar disorder patients and indicate the need in clinical practice for individualized treatment to reduce the risk for both patient and society related losses.

Lithium as add-on to quetiapine XR in adult patients with acute mania: a 6-week, multicenter, double-blind, randomized, placebo-controlled study.

Quetiapine extended release (XR) and lithium are treatments with proven efficacy in acute mania. This randomized study evaluated the efficacy and safety of lithium or placebo as add-on to quetiapine XR in adult patients with manic or mixed symptoms of bipolar I disorder. In this 6-week, double-blind study (Trial D144AC00003), adult patients with DSM-IV-TR-diagnosed bipolar I disorder (current episode manic or mixed), a Young Mania Rating Scale (YMRS) total score ≥20, and score ≥4 on two of four core YMRS items were administered quetiapine XR (400 to 800 mg/day) and randomly assigned to receive add-on lithium (600 to 1,800 mg/day) or placebo. The primary efficacy end point was change in the YMRS total score from baseline to day 43, analyzed using a mixed-model for repeated measures (MMRM) approach. Secondary efficacy and safety end points were also measured. Rating scales were administered by trained staff. Three hundred fifty-six patients treated with quetiapine XR were randomized to add-on lithium (n = 173) or placebo (n = 183). Two hundred ninety-one patients (81.7%) completed the study. At day 43, least squares mean change in YMRS total score was -22.8 for add-on lithium and -20.1 for add-on placebo, a statistically significant treatment group difference of -2.69 (p < 0.001). On secondary measures, add-on lithium was associated with significant improvements in response, remission, illness severity, and overall illness versus add-on placebo (p < 0.05). The number needed to treat was 9.1 for response and 7.9 for remission for add-on lithium compared with add-on placebo. Lithium in combination with quetiapine XR was generally well tolerated, with a similar profile to quetiapine XR in combination with placebo. The addition of lithium to quetiapine XR therapy was associated with significantly greater efficacy than placebo as add-on and was generally well tolerated in patients with acute bipolar I mania. This study was registered under Clinicaltrials.gov Identifier NCT00931723.

Impact of extended-release quetiapine fumarate on hospitalization length and cost in schizophrenia and bipolar disorder patients: a retrospective, hospital-based, US-cohort analysis.

AIM: The aim was to evaluate the impact of quetiapine extended release (XR) on hospitalization length and cost in schizophrenia or bipolar disorder, versus quetiapine immediate release (IR), using Premier Perspective™ inpatient hospital database data. METHODS: Inpatient discharges classified within diagnosis-related group 430 (psychoses), prescribed quetiapine XR or IR, were identified. Patients had International Classification of Disease-9 diagnosis of schizophrenia or bipolar disorder. The impact of the XR formulation on hospitalization length and costs was assessed using generalized linear model analyses. RESULTS: A total of 30,429 discharges between 1 January 2008 and 30 June 2009 were analyzed. Patients who received quetiapine XR had significantly reduced hospitalization length (10.73% estimated reduction; p = 0.001) and cost (9.52% estimated reduction; p < 0.001), versus IR. This corresponds to a 1.0-day reduction in hospitalization (10.73% of 9.2 days) and US$532 reduction in hospitalization cost (9.52% of US$5588) per patient, based on least squares mean estimations. Evaluation of patient subpopulations suggested the reduction in length of hospitalization for quetiapine XR versus IR was driven mainly by patients with bipolar disorder, whereas cost reduction was driven mainly by patients with schizophrenia. CONCLUSION: Inpatient use of quetiapine XR in schizophrenia or bipolar disorder is associated with reduced hospitalization length and cost, possibly due to the faster titration schedule versus quetiapine IR.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. LIMITATIONS: 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. CONCLUSIONS: 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.

Subjective well-being in schizophrenia: a randomised controlled open-label 12-month non-inferiority study comparing quetiapine XR with risperidone (RECOVER).

UNLABELLED: This randomised 12-month open study analysed the effectiveness of quetiapine XR (400-800 mg) versus risperidone (2-6 mg) on subjective well-being in schizophrenia (NCT00600756). Primary objective was to demonstrate non-inferiority of quetiapine XR to risperidone in 6-month responder rate using the Subjective Well-Being under Neuroleptics scale (SWN-K) (per-protocol at Month 6 [PP 6] population). Non-inferiority was defined as the lower limit of the 95% confidence interval (CI) greater than -9.7% for the adjusted difference between quetiapine XR and risperidone. Secondary objectives included non-inferiority of quetiapine XR versus risperidone (lower limit of 95% CI greater than -7.5 points) for SWN-K change from baseline to Month 12 (PP 12). 798 patients were randomised (quetiapine XR, n=395; risperidone, n=403); at Month 12, 212 (54%) and 227 (56%) patients, respectively, completed the study. At Month 6, SWN-K responder rate in the PP 6 population was 65% (136/210) with quetiapine XR and 68% (158/232) with risperidone (adjusted treatment difference: -5.7%; 95% CI: -15.1, 3.7); thus, non-inferiority could not be established. SWN-K change from baseline to Month 12 was 23.2 points for quetiapine XR and 21.1 points for the risperidone group; treatment difference was 2.1 (95% CI: -0.8; 5.0); non-inferiority was established (PP 12). CONCLUSION: SWN-K response at 6 months was comparable between the two antipsychotics. However, with a lower than expected responder rate and a lower than expected number of evaluable patients in the PP 6 population, non-inferiority was not demonstrated. A secondary objective (SWN-K total score) established non-inferiority of quetiapine XR to risperidone at Month 12.

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.

BACKGROUND: Differences 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). OBJECTIVE: To compare treatment patterns, health care resource use, and costs in patients with bipolar disorder newly treated with quetiapine XR or quetiapine IR. METHODS: This 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). RESULTS: In 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. CONCLUSIONS: Treatment 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.

Pooled analysis of sustained response rates for extended release quetiapine fumarate as monotherapy or adjunct to antidepressant therapy in patients with major depressive disorder.

BACKGROUND: Clinical trials are not generally powered to analyze outcomes such as sustained response. We evaluated sustained response rates for patients with major depressive disorder receiving quetiapine XR as monotherapy or adjunct therapy. METHOD: Post hoc analyses of pooled data from four previously reported randomized, placebo-controlled studies of quetiapine XR 150 and 300 mg/day as monotherapy or adjunct therapy to ongoing antidepressant. Sustained response rates (≥50% reduction in MADRS total score at specific timepoint and each subsequent visit until Week 6) were calculated at Weeks 1, 2, and 4; rates were compared using a Cochran-Mantel-Haenszel analysis. RESULTS: In the monotherapy studies, the proportion of patients experiencing sustained response was greater with quetiapine XR 150 mg/day versus placebo at Week 2 (20.0% vs. 13.3%; p<0.05) and Week 4 (33.3% vs. 23.3%; p<0.01) (observed cases [OC]). The corresponding sustained response rates for quetiapine XR 300 mg/day were 18.0% (p=0.104) and 29.7% (p=0.063), respectively (OC). The proportion of patients experiencing sustained response was greater in the adjunct studies versus placebo at Weeks 2 and 4 for quetiapine XR 150 (Week 2, 30.1% vs. 15.2%, p<0.001; Week 4, 40.1% vs. 32.0%, p<0.05) and 300 mg/day (Week 2, 29.0% vs. 15.2%, p<0.001; Week 4, 42.0% vs. 32.0%, p<0.05) (OC). LIMITATIONS: Post hoc analyses, acute treatment period; no active comparator. CONCLUSIONS: Quetiapine XR as monotherapy (150 mg/day at Weeks 2 and 4) or adjunct to ongoing antidepressant therapy (150 and 300 mg/day at Weeks 2 and 4) increased sustained response rates versus placebo.

Effects of extended-release quetiapine fumarate on long-term functioning and sleep quality in patients with Generalized Anxiety Disorder (GAD): data from a randomized-withdrawal, placebo-controlled maintenance study.

BACKGROUND: This analysis evaluated effects of quetiapine XR maintenance treatment on functioning and sleep in patients with GAD. METHODS: Analysis of patient-reported data from a randomized-withdrawal, double-blind, placebo-controlled study of quetiapine XR monotherapy in GAD. Following open-label run-in (4-8 weeks) and a 12-18-week stabilization phase (quetiapine XR 50, 150, or 300 mg/day), eligible patients were randomized to continue on quetiapine XR or receive placebo for up to 52 weeks. Primary variable was time to an anxiety event. Secondary variables included the Sheehan Disability Scale (SDS) and Pittsburgh Sleep Quality Index (PSQI). RESULTS: In total, 432 patients were randomized (quetiapine XR, N=216; placebo, N=216). The risk of an anxiety event was significantly reduced for quetiapine XR vs. placebo (HR 0.19; 95% CI 0.12, 0.31; p<0.001). Quetiapine XR was more effective than placebo at maintaining SDS total scores (LSM change: -0.19 vs. 1.01; p=0.017) and non-work-related SDS domain score 'family life/home responsibilities' (-0.13 vs. 0.32; p=0.011), but not 'social life' (0.05 vs. 0.34; p=0.114). Quetiapine XR was more effective than placebo at maintaining the work-related SDS domain score 'days lost' (-0.05 vs. 0.11; p=0.027), but not 'work/school' (-0.10 vs. 0.29; p=0.051) or 'days underproductive' (0.06 vs. 0.13; p=0.619). PSQI global scores were reduced from randomization with quetiapine XR vs. placebo (0.39 vs. 1.60; p<0.001). LIMITATIONS: Lack of active-comparator arm, exclusion of patients with comorbid depression. CONCLUSIONS: In patients with GAD, long-term treatment with quetiapine XR (50-300 mg/day) monotherapy was effective at maintaining improvements in functioning and sleep quality.