Assessing the Reliability and Validity of the Sheehan Irritability Scale in Patients With Major Depressive Disorder.

OBJECTIVE: Irritability is a significant component in the clinical manifestation of major depressive disorder (MDD). The Sheehan Irritability Scale (SIS) was developed to assess irritability-related symptoms in patients with psychiatric disorders. Data from a phase 2 clinical trial (June 2008-July 2009) was utilized to evaluate the psychometric properties of the SIS. The trial population included patients diagnosed with MDD, according to DSM-IV and confirmed via the MINI diagnostic scale, who had inadequate response to citalopram. METHOD: The secondary analyses included 586 patients from the United States and India. Data from the SIS, depression severity measures (17-item Hamilton Depression Rating Scale [HDRS-17], Montgomery-Asberg Depression Rating Scale [MADRS], Quick Inventory of Depressive Symptomatology-Self-Report [QIDS-SR]), and other measures (Sheehan Disability Scale [SDS], Clinical Global Impressions-Severity of Illness scale [CGI-S]) were used in the psychometric evaluation. All statistical tests used a significance level of .05 unless otherwise noted. RESULTS: Internal consistency (0.92-0.99) and test-retest reliability (0.83 to 0.98) were excellent. Concurrent validity was demonstrated through strong correlations between the SIS total score and HDRS-17, QIDS-SR, SDS, CGI-S, and MADRS scores. SIS total scores were significantly different by clinical severity level (P < .001). Minimally important difference estimates suggest that a 7- to 8-point change in the SIS total score may be clinically meaningful. CONCLUSIONS: The SIS has excellent reliability, acceptable validity, and good responsiveness, making the SIS appropriate for use in clinical research and practice. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00692445.

Content validity of the Sheehan Irritability Scale in patients with major depressive disorder.

The Sheehan Irritability Scale (SIS) measures the frequency, severity, and impairment associated with irritability in psychiatric patients. The content validity of the SIS in patients with major depressive disorder (MDD) has not been evaluated. A cross-sectional, qualitative research study was conducted to assess the content validity of the SIS among patients with MDD. One-on-one interviews were conducted, starting with open-ended questions to evaluate the consistency of the SIS content with patient experiences of irritability. Participants then completed the SIS and cognitive interviews around the comprehension of the SIS content (instructions, items, response options). Participants included 24 patients diagnosed with MDD who had an inadequate response to an antidepressant treatment. The sample was: 50.4 mean years, 66.7% female, and 91.7% white racial background. All concepts on the SIS were spontaneously mentioned by at least one participant, and when probed about the symptoms, the majority of participants (66.7-100%) reported the concepts being part of their experience. The majority of participants (70.8-100%) understood the SIS instructions, items, and response scales. This study provides evidence of content validity of the SIS in patients diagnosed with MDD, supporting the use as a measure of irritability in patients with 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.

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.

Economic and humanistic burden of illness in generalized anxiety disorder: an analysis of patient survey data in Europe.

BACKGROUND: Whilst studies suggest that generalized anxiety disorder (GAD) represents a considerable health care burden in Europe, there is a paucity of published evidence. This study investigated the burden of illness associated with GAD across five European countries (France, Germany, Italy, Spain, and the UK). METHODS: Information from the 2008 European National Health and Wellness Survey database was analyzed. Bivariate, multivariate, and cost analyses were used to compare patients with GAD and propensity-matched controls. RESULTS: Compared with non-GAD controls, patients with GAD had more comorbidities and were more likely to smoke but less likely to be employed, use alcohol, or take exercise. They also had significantly worse health-related quality of life, and significantly greater work impairment and resource use, which increased as GAD severity increased. Within-country analyses demonstrated results similar to those for the five European countries overall, with the largest differences in resource use between patients with GAD and non-GAD controls documented in France and Germany. The average mean differences in direct costs were relatively small between the GAD groups and controls; however, indirect costs differed substantially. Costs were particularly high in Germany, mainly due to higher salaries leading to higher costs associated with absence from work. The limitation of this study was that the data were from a self-reported Internet survey, making them subject to reporting bias and possibly sample bias. CONCLUSION: Across all five European countries, GAD had a significant impact on work impairment, resource use, and economic costs, representing a considerable individual and financial burden that increased with severity of disease. These data may help us to understand better the burden and costs associated with GAD.

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.

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

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: Quetiapine XR (monotherapy or adjunct therapy) had an impact on sexual function that was comparable with placebo.

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.

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.

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

BACKGROUND: Major 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. METHODS: Prospectively 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 50-300 mg/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. RESULTS: In 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). LIMITATIONS: Lack of active-comparator arm, flexible-dose design, acute treatment period. CONCLUSIONS: Quetiapine XR monotherapy improved QoL and sleep in elderly patients with MDD.

Quetiapine XR monotherapy in major depressive disorder: a pooled analysis to assess the influence of baseline severity on efficacy.

The efficacy of quetiapine XR was investigated in patients with major depressive disorder and differing levels of baseline severity. Pooled data from four placebo-controlled monotherapy studies of quetiapine XR (50-300 mg/day) were analyzed. Post-hoc analyses were carried out to assess change from baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) total score at endpoint (week 6 or 8) to week 1, and response (≥50% reduction in MADRS total score) and remission (MADRS total score≤10) rates at endpoint for all patients and six baseline severity cohorts (MADRS total score ≥24, ≥26, ≥28, ≥30, ≥32, and ≥34). In total, 1752 patients (all patients) were evaluated (MADRS score at baseline: ≥24, n=1601; ≥26, n=1467; ≥28, n=1269; ≥30, n=1038; ≥32, n=745; and ≥34, n=500). At endpoint, quetiapine XR reduced MADRS total score in all patients (P<0.001) and each severity cohort (≥24, ≥26, ≥28, ≥30, and ≥32, P<0.001; ≥34, P<0.01) versus placebo. Quetiapine XR also improved MADRS total score at week 1, response rates for each severity cohort, and remission rates in five out of six severity cohorts, versus placebo. Quetiapine XR monotherapy showed antidepressant effects in patients with major depressive disorder across different levels of baseline severity.

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

BACKGROUND: We evaluated the effects of once-daily extended-release quetiapine fumarate (quetiapine XR) on patient-reported outcomes in generalized anxiety disorder (GAD). METHODS: This 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). RESULTS: The 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. CONCLUSION: Quetiapine 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.

Cost effectiveness of quetiapine in patients with acute bipolar depression and in maintenance treatment after an acute depressive episode.

BACKGROUND: Bipolar disorder has a significant impact upon a patient's quality of life, imposing a considerable economic burden on the individual, family members and society as a whole. Several medications are indicated for the acute treatment of mania and depression associated with bipolar disorder as well as for maintenance therapy; however, these have varying efficacy, tolerability and costs. OBJECTIVE: The objective of this study was to develop a new discrete-event simulation model to analyse the long-term consequences of pharmacological therapy for the management of bipolar I and II disorders (acute treatment of episodes of mania and depression as well as maintenance therapy). METHODS: Probabilities of remission and relapse were obtained from clinical trial data and meta-analyses. Costs (year 2011 values) were assessed from a UK healthcare payer's perspective, and included pharmacological therapy and resource use associated with the treatment of mood events and selected adverse events. The health effects were measured in terms of QALYs. RESULTS: For a patient starting with acute depression or in remission at 40 years of age (which was the average age in the clinical trials), quetiapine 300 mg/day was a cost-effective strategy compared with olanzapine 15 mg/day over a 5-year time frame. With acute bipolar depression as a starting episode, the 5-year medical costs were £323 higher and QALYs were 0.038 higher for quetiapine compared with olanzapine, corresponding to a cost-effectiveness ratio of £8600 per QALY gained. CONCLUSION: Compared with olanzapine, the results suggest that quetiapine is cost effective as a maintenance treatment for bipolar depression.

Understanding the relationships between health outcomes in generalized anxiety disorder clinical trials.

BACKGROUND AND AIMS: The Wilson-Cleary health outcomes model is a hypothesized pathway linking traditional clinical variables to health-related quality of life (HRQL). This study tested the application of the Wilson-Cleary model to a patient population with generalized anxiety disorder (GAD) using longitudinal clinical trial data. METHODS: These secondary analyses pooled data from three similar 8-week, placebo-controlled, double-blind, randomized, multicenter trials of quetiapine XR therapy in GAD. Relevant health assessments for the model concepts included the Clinical Global Impression-Severity of Illness, Hamilton Rating Scale for Anxiety, the Pittsburgh Sleep Quality Index and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form. A lagged path model tested whether the hypothesized relationships at baseline and week 8 between the concepts of the adapted Wilson-Cleary model were consistent with the observed data. RESULTS: The resulting model fit the data (RMSEA = 0.077; CFI = 0.98; NFI = 0.96) and explained 56% of the variance in overall quality of life assessment at baseline and 69% of the variance in this assessment at week 8. Moderate to strong relationships between the adjacent hypothesized concepts support the specified model. CONCLUSION: This adapted Wilson-Cleary model for health outcomes validated in GAD should improve the understanding and usefulness of health status measurements in this condition and increase the applications of this model to other clinical trial data.

Assessment of quality of life enjoyment and satisfaction questionnaire-short form responder thresholds in generalized anxiety disorder and bipolar disorder studies.

Interpretation of change over time in patient-reported outcomes requires appropriate responder definitions. This study compares responder definitions for the short-form version of the Quality of Life Enjoyment and Satisfaction Questionnaire [Q-LES-Q(SF)] in populations with generalized anxiety disorder (GAD) and bipolar disorder. A review of the Q-LES-Q(SF) literature published in English from 1993 through May 2009 identified publications using the Q-LES-Q(SF) in GAD or bipolar disorder clinical trials. In six relevant articles reporting Q-LES-Q(SF) responder definitions in GAD or bipolar disorder, two methods for defining responders emerged: (i) return to a score within 10% of community norms for the Q-LES-Q(SF); and (ii) a change score at or greater than the condition-specific mean change achieved by patients with minimal improvement on the Clinical Global Impression-Improvement (CGI-I) at study endpoint or a 1-point decrease on the CGI-Severity scale between baseline and study endpoint. The magnitude of the CGI-I based responder thresholds differed across mental health conditions. Use of the Q-LES-Q(SF) community norms as a responder definition is discouraged. A responder definition needs to be investigated within each condition or disease using appropriate anchors, and may not be generalizable from one condition or disease to another.

Assessing health-related quality of life in generalized anxiety disorder using the Quality Of Life Enjoyment and Satisfaction Questionnaire.

Generalized anxiety disorder (GAD) is a chronic illness that leads to substantial impairments in quality of life. This post-hoc analysis used combined data from three 8-week quetiapine extended-release trials to investigate the reliability, validity, and responsiveness of the Short Form of the Quality of Life Enjoyment and Satisfaction Questionnaire [Q-LES-Q (SF)] in 2588 patients with GAD. The baseline Q-LES-Q (SF) score showed a Cronbach's alpha value of 0.86, indicative of reliability. Validity analyses for Q-LES-Q (SF) identified significant correlations with clinical efficacy measures (r>0.34 at week 8; P<0.001) and significant discrimination between patient groups categorized by symptom severity (P<0.001). Responsiveness was shown by significant differences in mean changes in Q-LES-Q (SF) scores at week 8 between patients defined according to the Hamilton Rating Scale for Anxiety response or remission criteria (P<0.001). The minimum clinically important Q-LES-Q (SF) score change was identified to be 6.80 points. Using this definition, response rates were significantly greater with quetiapine extended-release 150 mg versus placebo in individual trials and the combined population (P < or = 0.02). This analysis shows the overall reliability, validity, and responsiveness of the Q-LES-Q (SF) as a measure of overall quality of life and satisfaction in patients with GAD.

Long-acting risperidone in young adults with early schizophrenia or schizoaffective illness.

BACKGROUND: Treatment with long-acting injectable risperidone was evaluated in young adults likely to be in the early stages of schizophrenia or schizoaffective disorder. METHOD: An open-label 50-week trial included young adults (men aged 18-25 years and women aged 18-30 years). RESULTS: Sixty-six young adults received at least 1 injection of long-acting risperidone (25 or 50 mg) every two weeks; 64% of the patients completed the 50-week trial. A mode dose of 25 mg/14 days was received by 23 patients and 50 mg/14 days by 43 patients. Mean PANSS scores improved significantly from baseline at each time point, with 64% of the patients showing clinical improvement (>or=20% reduction in PANSS total scores) at endpoint. Patient-rated quality of life (SF-36 scores) improved and patients' attitudes toward the medication were positive (DAI scores). Severity of movement disorders (ESRS) and injection-site pain ratings were low throughout the trial. Results were similar in the population of other (older) patients. CONCLUSIONS: Long-acting risperidone was associated with clinical benefits in stable young adults with early schizophrenia or schizoaffective illness.

Cost effectiveness of long-acting risperidone injection versus alternative antipsychotic agents in patients with schizophrenia in the USA.

The availability of long-acting risperidone injection may increase adherence and lead to improved clinical and economic outcomes for individuals with schizophrenia. The objective of this study was to assess the cost effectiveness of long-acting risperidone, oral risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, and haloperidol depot in patients with schizophrenia over 1 year from a healthcare system perspective. Published medical literature, unpublished data from clinical trials and a consumer health database, and a clinical expert panel were utilized to populate a decision analytical model comparing the seven treatment alternatives. The model captured rates of patient compliance, the rates, frequency and duration of relapse, incidence of adverse events, and healthcare resource utilization and associated costs. Primary outcomes were expressed in terms of percentage of patients relapsing per year, number of relapse days per year (number and duration of relapses per patient per year), and total direct 2003 medical cost per patient per year. On the basis of model projections, the proportions of patients experiencing a relapse requiring hospitalization in 1 year were 66% for haloperidol depot, 41% for oral risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole, and 26% for long-acting risperidone, whereas the proportions of patients with an exacerbation not requiring hospitalization were 60% for haloperidol depot, 37% for oral risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole, and 24% for long-acting risperidone. The mean number of days of relapse requiring hospitalization per patient per year were 28 for haloperidol depot, 18 for oral risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole, and 11 for long-acting risperidone, whereas the mean number of days of exacerbation not requiring hospitalization were eight for haloperidol depot, five for oral risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole, and three for long-acting risperidone. This would translate into direct medical cost savings with long-acting risperidone compared with oral risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, and haloperidol depot of US dollars 161, 1425, 508, 259, 1068, and 8224, respectively. These findings were supported by sensitivity analyses. The utilization of long-acting risperidone is predicted to result in better clinical outcomes and lower total healthcare costs than its comparators, oral risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, and haloperidol depot. Long-acting risperidone may therefore be a cost saving therapeutic option for patients with schizophrenia.