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Background: Inadequate efficacy of current intranasal steroids in chronic rhinosinusitis (CRS) is attributable to ineffective and/or inconsistent drug delivery to target anatomic sites. A new exhalation delivery system with fluticasone (EDS‐FLU) may improve outcomes by significantly increasing superior/posterior corticosteroid delivery. A study was conducted to assess the long‐term efficacy and safety outcomes of EDS‐FLU in individuals with CRS. Methods: This was a 12‐month, multicenter, single‐arm study evaluating the safety and efficacy of EDS‐FLU 372 μg twice daily in CRS patients (with [n = 34] or without [n = 189] nasal polyps [NP]). Efficacy assessments by serial nasal endoscopy and patient report included: 22‐item Sino‐Nasal Outcome Test (SNOT‐22), NP grade, standardized surgical indicator assessment, Lund‐Kennedy score, and Patient Global Impression of Change. Adverse event (AE) evaluations included nasal endoscopy. Additional safety and efficacy outcomes were assessed. Results: Of 223 patients who received EDS‐FLU, 96% reported prior corticosteroid use and 29% prior sinus surgery. The EDS‐FLU AE profile was similar to conventional intranasal steroids studied in similar populations. Most patients (87%) reported symptom improvement. Through 12 months, mean SNOT‐22 scores improved by −21.5 and −21.1 for CRS with and without NP, respectively. Among patients with NP, 54.2% had polyp elimination in at least 1 nostril and 83.3% had ≥1‐point improvement in polyp grade. Conclusion: Over 1 year of treatment in CRS with and without NP, EDS‐FLU 372 μg twice daily was well tolerated and produced improvements across a broad range of objective and subjective measures. EDS‐FLU may be a desirable new option for patients with this condition. [ABSTRACT FROM AUTHOR]

Objective: The authors compared paliperidone extended-release and quetiapine in patients with recently exacerbated schizophrenia requiring hospitalization. Method: In a 6-week double-blind study, inpatients with a recent exacerbation of schizophrenia were randomly assigned to treatment with paliperidone extended-release, quetiapine, or placebo. A 2-week monotherapy phase was followed by a 4-week additive-therapy phase. Target doses were at the upper end of recommended ranges: paliperidone extended-release, 9 or 12 mg/day, and quetiapine, 600 or 800 mg/day. The primary endpoint was the difference in mean total change score on the Positive and Negative Syndrome Scale (PANSS) between paliperidone extended-release and quetiapine at the 2-week monotherapy phase endpoint. Results: Six-week completion rates were 77.5% (124/160) with paliperidone extended-release, 66.7% (106/159) quetiapine, and 63.8% (51/80) placebo. Improvement in mean PANSS total change score was greater with paliperidone extended-release than with quetiapine from day 5 (-11.4 versus -8.2) through the monotherapy phase endpoint (-23.4 versus -17.1). only paliperidone extended-release showed significantly greater PANSS improvement compared with placebo at 2 weeks. At the 6-week study endpoint, there was a significantly greater improvement with paliperidone extended-release compared with quetiapine despite similar use of additive therapy (predominantly other antipsychotics). Common adverse events with paliperidone extended-release, quetiapine, and placebo, respectively, were tremor (13.9%, 5.0%, 7.5%), somnolence (8.9%, 11.9%, 1.3%), insomnia (10.1%, 9.4%, 11.3%), and headache (12.0%, 7.5%, 13.8%). Six-week adverse event-related discontinuation rates were 6.3%, 10.1%, and 6.3%, respectively, in the paliperidone extended-release, quetiapine, and placebo groups. Conclusions: Compared with quetiapine, paliperidone extended-release improved symptoms earlier and to a greater degree in patients with recently exacerbated schizophrenia requiring hospitalization, with no unexpected tolerability findings. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder has high prevalence, morbidity, and mortality. Inadequate results with antidepressants have prompts addition of a nonstandard treatment (augmentation therapy).Objective: To assess whether augmentation therapy with risperidone reduces symptoms and increases response to antidepressant therapy and remission of depression in adults.Design: Multicenter, double-blind, placebo-controlled, randomized trial conducted from 19 October 2004 to 17 November 2005.Setting: 75 primary care and psychiatric centers.Patients: 274 outpatient adults with major depressive disorder that was suboptimally responsive to antidepressant therapy.Intervention: After a 4-week run-in period to ensure insufficient response to standard antidepressants, patients were randomly assigned to receive risperidone, 1 mg/d, or placebo for 6 weeks. After 4 weeks, the dosage of risperidone was increased to 2 mg/d in some cases.Measurements: Symptoms were measured by using the 17-item Hamilton Rating Scale for Depression (HRSD-17). Other outcomes were response to therapy, remission of depression, and various clinician- and patient-rated assessments.Results: Of the intention-to-treat population (268 patients), 81% (111 of 137) who received risperidone and 87.8% (115 of 131) who received placebo completed 6 weeks of double-blind treatment. Mean (+/-SE) HRSD-17 scores improved more in the risperidone augmentation group than in the placebo group (13.4 +/- 0.54 vs. 16.2 +/- 0.53; difference, -2.8 +/- 0.72 [95% CI, -4.2 to -1.4]; P <0.001). More risperidone recipients than placebo recipients experienced remission of depression (24.5% [26 of 106] vs. 10.7% [12 of 112]; P = 0.004) and had a response (46.2% [49 of 106] vs. 29.5% [33 of 112]; P = 0.004). Headache (8.8% of risperidone recipients vs. 14.5% of placebo recipients), somnolence (5.1% vs. 1.5%), and dry mouth (5.1% vs. 0.8%) were the most frequently reported adverse events.Limitations: Patients were receiving many different antidepressants, and the duration of augmentation therapy was limited.Conclusion: Risperidone augmentation produced a statistically significant mean reduction in depression symptoms, substantially increased remission and response, and improved other patient- and clinician-rated measures. ClinicalTrials.gov registration number: NCT00095134. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder has high prevalence, morbidity, and mortality. Inadequate results with antidepressants have prompts addition of a nonstandard treatment (augmentation therapy). Objective: To assess whether augmentation therapy with risperidone reduces symptoms and increases response to antidepressant therapy and remission of depression in adults. Design: Multicenter, double-blind, placebo-controlled, randomized trial conducted from 19 October 2004 to 17 November 2005. Setting: 75 primary care and psychiatric centers. Patients: 274 outpatient adults with major depressive disorder that was suboptimally responsive to antidepressant therapy. Intervention: After a 4-week run-in period to ensure insufficient response to standard antidepressants, patients were randomly assigned to receive risperidone, 1 mg/d, or placebo for 6 weeks. After 4 weeks, the dosage of risperidone was increased to 2 mg/d in some cases. Measurements: Symptoms were measured by using the 17-item Hamilton Rating Scale for Depression (HRSD-17). Other outcomes were response to therapy, remission of depression, and various clinician- and patient-rated assessments. Results: Of the intention-to-treat population (268 patients), 81% (111 of 137) who received risperidone and 87.8% (115 of 131) who received placebo completed 6 weeks of double-blind treatment. Mean (±SE) HRSD-17 scores improved more in the risperidone augmentation group than in the placebo group (13.4 ±0.54 vs. 16.2± 0.53; difference, -2.8 ± 0.72 [95% CI, ±4.2 to ±1.4]; P ±0.001). More risperidone recipients than placebo recipients experienced remission of depression (24.5% [26 of 106] vs. 10.7% [12 of 112]; P ± 0.004) and had a response (46.2% [49 of 106] vs. 29.5% [33 of 112]; P= 0.004). Headache (8.8% of risperidone recipients vs. 14.5% of placebo recipients), somnolence (5.1% vs. 1.5%), and dry mouth (5.1% vs. 0.8%) were the most frequently reported adverse events. Limitations: Patients were receiving many different antidepressants, and the duration of augmentation therapy was limited. Conclusion: Risperidone augmentation produced a statistically significant mean reduction in depression symptoms, substantially increased remission and response, and improved other patient- and clinician-rated measures. [ABSTRACT FROM AUTHOR]

Objective: The use of adjunctive psychotropics and the costs of polypharmacy in patients randomized to receive risperidone or quetiapine were compared in a placebo-controlled double-blind study conducted in India, Romania, and the United States.Methods: The efficacy and safety of risperidone, quetiapine, and placebo were compared in a 14-day monotherapy phase in patients experiencing an acute exacerbation of symptoms of schizophrenia or schizoaffective disorder. This was followed by a 28-day, additive-therapy phase during which addition of antipsychotics or other psychotropic medications was permitted. Risperidone was received by 153 patients in the monotherapy phase and 133 in the additive therapy phase, quetiapine by 156 and 122, respectively, and placebo by 73 and 53. Rates of polypharmacy were examined using the Cochran-Mantel-Haenszel, Kaplan-Meier, and Cox regression methods. Costs of polypharmacy were analyzed by non-parametric Wilcoxon 2-sample tests.Results: Primary study results have been reported elsewhere (Potkin et al., Schizophr Res 2006;85:254-65). Mean (+/-SD) doses at the additive-therapy baseline were 4.7 +/- 0.9 mg/day of risperidone and 579.0 +/- 128.9 mg/day of quetiapine. Additional psychotropics were received by 36% of the risperidone group, 58% of the quetiapine group (p < 0.01), and by 58% of the placebo group. Antipsychotics accounted for > 95% of the added psychotropics, the most common being olanzapine and haloperidol. The relative risk (quetiapine vs. risperidone) for antipsychotic polypharmacy was 1.90 (p = 0.001; 95% CI 1.29, 2.80). The mean projected cost of additional antipsychotics per randomized patient during the additive-therapy phase was $57.03 in the risperidone group and $101.64 in the quetiapine group (p < 0.01).Conclusions: The results confirm earlier reports of higher rates of polypharmacy with quetiapine than with risperidone. The findings also reveal substantial between-treatment differences in costs associated with polypharmacy. Limitations of the study include that the study was of short duration and that a high proportion of patients were recruited from countries other than the United States. [ABSTRACT FROM AUTHOR]

Abstract: Objective: This study compared the effects of atypical antipsychotics (risperidone or quetiapine) with placebo and with each other in recently exacerbated patients with schizophrenia requiring hospitalization. Methods: This international, randomized, double-blind study included a 2-week monotherapy phase followed by a 4-week additive therapy phase. Recently exacerbated patients with schizophrenia or schizoaffective disorder (DSM-IV) were randomized (2:2:1) to risperidone (n =153), quetiapine (n =156), or placebo (n =73). Target doses were 4 or 6 mg/day of risperidone and 400 or 600 mg/day of quetiapine by day 5, with the ability to increase to 600 or 800 mg/day of quetiapine on day 8. The main outcome measures were the total Positive and Negative Syndrome Scale (PANSS) and need for additional psychotropic medications. Results: Monotherapy Phase: The combined atypical antipsychotic group (n =308) reached borderline superiority to placebo (n =71) at the 2-week endpoint on mean change in total PANSS score (−24.1±1.2 and −20.2±2.0, respectively; p =0.067). The change in the atypical group was driven by the improvement with risperidone (−27.7±1.5 vs. −20.2±2.0 with placebo, p <0.01; and vs. −20.5±1.5 with quetiapine, p <0.01); the improvement with quetiapine was similar to placebo, p =0.879. Results were similar on other efficacy endpoints. Additive Therapy Phase: Additional psychotropics were prescribed to fewer (p <0.01) risperidone (36%) than quetiapine (53%) or placebo patients (59%). The overall discontinuation rate was 18%, 26%, and 38%, respectively. Risperidone, compared with placebo, was associated with more parkinsonism, akathisia, plasma prolactin changes, and weight gain; while quetiapine was associated with more somnolence, sedation, dizziness, constipation, tachycardia, thyroid dysregulation, and weight gain. Conclusion: While the combined atypical antipsychotic group did not experience greater improvements than the placebo group, risperidone, but not quetiapine, was significantly superior in all measured domains to placebo in the management of recently exacerbated hospitalized patients with schizophrenia or schizoaffective disorder, with no unexpected tolerability findings. [Copyright &y& Elsevier]

Background: Patient satisfaction with antipsychotic treatment is important. Limited evidence suggests that satisfaction is associated with symptom improvement and compliance. Predictors of patient satisfaction with antipsychotic medication were examined in a study of patients with a recent exacerbation of schizophrenia. Methods: Data are from a randomized, double-blind trial comparing risperidone (n = 152), quetiapine (n = 156), and placebo (n = 73). Medication Satisfaction Questionnaire (MSQ) was completed after 14 days of treatment and after 6 weeks at last study visit. Results: Medication satisfaction at both time points was significantly associated in multiple regression analysis with improvement on 3 Positive and Negative Syndrome Scale (PANSS) factor scores (positive symptoms p < .01; uncontrolled hostility/excitement, p < .0005; anxiety/depression, p < .04) and treatment with risperidone (p < .03); at day 14, significant association was also found with older age (p = .01). At both time points, predictor variables explained over 30% of the variance in medication satisfaction. Change in Hamilton Depression Scale, prolactin levels, sex, and reported adverse events of extrapyramidal symptoms, sedation, and movement disorders were not significant predictors of satisfaction. Lower level of medication satisfaction at day 14 was associated with earlier discontinuation in the trial at week 6 end point. A focused principal components analysis of PANSS factors and MSQ suggested that medication satisfaction relates to 3 groups of factors in descending order of magnitude: lower levels of (a) uncontrolled hostility/excitement, (b) positive symptoms, and (c) negative symptoms, disorganized thoughts, and anxiety/depression. Conclusion: Results give further support that treatment satisfaction is positively associated with symptom improvement, particularly psychotic symptoms, and suggest that satisfaction may also be related to compliance, as those who were more satisfied remained in the trial for a longer period of time. [ABSTRACT FROM AUTHOR]

Objective: The Readiness for Discharge Questionnaire (RDQ) was developed as an easy to use tool for assessing readiness for discharge, independent of socio-economic factors, for inpatients with schizophrenia. The psychometric properties of the RDQ are described. Methods: The RDQ consists of 6 items assessing suicidality/homicidality, control of aggression/impulsivity, activities of daily living, medication-taking, delusions/hallucinations interfering with functioning and global status. A final yes/no question assesses readiness for discharge. Data derived from 3 studies (500 patients in 3 countries) were used in analyzing inter-rater and test-retest reliability, content and construct validity, and sensitivity to change. Results: The inter-rater reliability was high for all items of the RDQ (reliability coefficients >0.9) and moderate to high for the readiness for discharge status (Session I: 84% agreement, kappa 0.39, polychoric correlation r=0.81; Session II: 89% agreement, kappa 0.63, polychoric correlation r=0.81. Test-retest reliability was also high for all items of the RDQ (reliability coefficients >0.9) and the readiness for discharge status (kappa=0.743; tetrachoric correlation r=0.819). Overall, 84% of the raters agreed (mean score=5.0 of possible 6.0) that the RDQ was useful in assessing a patient's readiness for discharge from the hospital. Evidence of good construct validity included significant correlations with PANSS total and factor scores, and a significant relationship with actual discharge. Significantly more patients with symptom improvement were judged ready for discharge (compared to those without symptom improvement), indicating that the RDQ was sensitive to change over time. Conclusions: The RDQ has favorable reliability and validity properties, and is an easy to use instrument in research studies for assessing readiness for discharge of inpatients with schizophrenia. Additional work in naturalistic settings is required to further validate the instrument for routine clinical use. [ABSTRACT FROM AUTHOR]