Cognitive function with long-term risperidone in children and adolescents with disruptive behavior disorder.

OBJECTIVE: The aim of this study was to evaluate cognitive effects from long-term risperidone treatment for disruptive behavior disorders (DBDs) in children and adolescents. METHODS: Patients 5-17 years old with DBDs and an intelligence quotient (IQ) > or =54 were randomized to flexibly dosed risperidone or placebo in a 6-month recurrence prevention trial. Cognitive function was assessed with a modified California Verbal Learning Test for Children (MVLT-C) and Continuous Performance Test (CPT), which assessed vigilance through computer testing with both an easy and a hard test. Somnolence was also evaluated throughout treatment. Clinically meaningful treatment effects were assessed as changes of > or =0.5 or > or =1.0 standard deviation (SD) from baseline. RESULTS: A total of 284 subjects participating in 6-month maintenance treatment had both baseline and end point cognition assessments and were included in this analysis. Significant improvements from baseline occurred in risperidone-treated subjects for CPT hard hit rates and discrimination ability (Pr) (p < 0.05 for both), and in placebo subjects for CPT easy false alarms rates (p < 0.001) and hard Pr (p < 0.05). Both the easy and hard CPTs correct mean response time worsened with placebo. The MVLT-C short-delay free recall improved significantly for both risperidone and placebo. After adjusting for country, somnolence, age, IQ, and baseline scores, no significant differences were noted in cognition between treatment groups. Clinically meaningful changes were generally similar for risperidone and placebo patients. Mild to moderate somnolence occurred in only 2% of patients treated with either risperidone or placebo. The change in cognitive testing was not different in subjects experiencing somnolence as an adverse event (AE) compared with subjects not experiencing somnolence. CONCLUSIONS: Risperidone treatment resulted in no decline in cognitive function among children and adolescents. These results extend on previous results from risperidone studies in DBD in patients with lower IQ.

Randomized, double-blind, placebo-controlled study of paliperidone extended-release and quetiapine in inpatients with recently exacerbated schizophrenia.

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.

One-week dose titration of extended release galantamine in patients with Alzheimer's disease.

BACKGROUND: Our purpose was to assess the safety and tolerability of extended-release galantamine (GAL-ER), using a 1-week dose titration in Alzheimer's patients. METHODS: An open-label, 12-week, multicenter study was performed (n = 82). Results were compared with findings from a placebo-controlled trial using a 4-week titration of GAL-ER and immediate-release galantamine. The primary analysis compared incidences of adverse events (AEs). RESULTS: Although not statistically significant, more patients in the 1-week titration study experienced an AE. More patients with a 1-week titration had at least one prespecified gastrointestinal (GI) AE. These findings correlated with a higher baseline incidence of GI disturbances. Four patients experienced serious AEs; no deaths occurred. Mean Mini-Mental State Examination scores improved by 1.8 and 1.9 points at weeks 4 and 12, respectively. CONCLUSIONS: A 1-week titration of GAL-ER was generally safe and well tolerated, with a potential risk of more GI side effects. A 1-week titration may permit dosing flexibility and promote increased adherence to medication regimens.

Psychotic symptoms in patients with bipolar mania.

BACKGROUND: Psychosis has been identified in as many as 68% of patients with bipolar mania. This analysis identified psychotic symptoms in these patients. METHODS: Data were from two placebo-controlled, 3-week studies in patients with an acute episode of bipolar mania. Symptoms were identified by the 30-item Positive and Negative Syndrome Scale (PANSS; item ratings, 1 = absent to 7 = extremely severe), the Young Mania Rating Scale, and the Global Assessment Scale. RESULTS: Psychotic features at study entry were diagnosed in 264 (51.3%) of the 515 patients. At baseline, these patients had significantly more severe scores on the PANSS, Young Mania Rating Scale, and Global Assessment Scale than patients without psychotic features. Patients with psychotic features had mean (+/-SD) scores of mild (3) or greater on six PANSS items: grandiosity (4.5+/-1.4), delusions (4.4+/-1.4), lack of judgment/insight (4.1+/-1.5), excitement (3.9+/-1.3), suspiciousness/persecution (3.1+/-1.6), and hostility (3.1+/-1.5). Grandiosity symptoms of delusional proportions (scores > or = 4) were noted in 205 (78%) of patients with a diagnosis of psychotic features and in 113 (45%) patients without the diagnosis. LIMITATIONS: The study was not specifically designed to assess patients with psychotic features and the PANSS was developed to evaluate symptoms of schizophrenia. CONCLUSIONS: These findings support prior reports indicating high rates of psychosis in patients with bipolar mania and identify the most prominent symptoms in these patients.

Dimensions of psychosis in patients with bipolar mania as measured by the positive and negative syndrome scale.

BACKGROUND: Psychosis is present in 50% or more of patients with bipolar mania and is commonly evaluated in clinical research by means of the Positive and Negative Syndrome Scale (PANSS). The aim of the present analysis was to investigate the psychotic dimensions of bipolar disorder and its contributing symptoms based on a factor analysis of baseline PANSS scores and to compare them with those identified in studies of patients with schizophrenia and bipolar disorder. SAMPLING AND METHODS: Baseline data were analyzed from two 3-week, double-blind, placebo-controlled studies of risperidone monotherapy for acute mania associated with bipolar I disorder (n = 535). Inclusion criteria were a DSM-IV diagnosis of bipolar I disorder with manic features, with or without psychotic features, age > or =18 years, and mean baseline Young Mania Rating Scale scores > or =20. A principal component analysis of the 30 PANSS item scores of the 535 patients with a diagnosis of a manic episode at baseline was conducted. RESULTS: Five factors were extracted by the analysis: anxiety (13.4% of the variance), negative symptoms (12.3%), depression (10.5%), excitement (10.3%), and positive symptoms (8.7%). Similar factors, in particular the negative, excitement, and positive factors, have been identified in patients with schizophrenia. There was an absence of a cognitive factor supporting the notion that bipolar patients may present fewer cognitive symptoms. CONCLUSION: The results of the present analysis and those of other studies indicate similarities in psychotic symptom domains, as measured by the PANSS, in patients with bipolar mania and schizophrenia. Future analyses will address the effects of treatment on the identified factors.

Effects of galantamine on measures of attention: results from 2 clinical trials in Alzheimer disease patients with comparisons to donepezil.

Deficits in attention are present early in the course of Alzheimer disease (AD). Acetylcholine receptors are appealing molecular targets for intervention as cholinergic pathways are involved in the neurobiology of attention. For this reason, measures of attention were included in 2 independent, multicenter, randomized, parallel, controlled trials in subjects with AD comparing the effects of galantamine, an acetylcholinesterase inhibitor and postulated nicotinic receptor modulator, and donepezil, an acetylcholinesterase inhibitor. The attention battery of the Cognitive Drug Research computerized assessment system was used in both trials. Small magnitude, positive signals were observed for simple and choice reaction times for both compounds. Attention task performance tended to improve early for galantamine-treated subjects. A consistent temporal pattern of improvement was not observed in donepezil-treated subjects. Quantitative findings appeared more pronounced in subjects with moderate AD. Galantamine's proposed action as a nicotinic receptor modulator may bear on these findings. Improved attention may have positive effects on cognitive and functional outcomes for AD patients, although this hypothesis requires further study and validation.

Ethnic heterogeneity in glucoregulatory function during treatment with atypical antipsychotics in patients with schizophrenia.

OBJECTIVE: Atypical antipsychotics induce weight gain and are linked to increased diabetes risk, but their relative impact on factors that elevate disease risk are unknown. METHODS: We performed a 6-month, randomized, double-blind study to evaluate the effects of risperidone and olanzapine in patients with schizophrenia. At baseline and weeks 6 and 24, we quantified: (1) total adiposity by DEXA, (2) visceral adiposity by abdominal CT, and (3) insulin sensitivity (SI) and (4) pancreatic function ("disposition index", DI) by intravenous glucose tolerance test. RESULTS: At baseline, groups (risperidone: n=28; olanzapine: n=31) were overweight or obese by body mass index (risperidone: 28.4+/-5.4, olanzapine: 30.6+/-7.0kg/m2). Both drugs induced weight gain (p<0.004). Total adiposity was increased by olanzapine at 6 weeks (p=0.0006) and by both treatments at 24 weeks (p<0.003). Visceral adiposity was increased by olanzapine and risperidone by 24 weeks (p<0.003). S(I) did not deteriorate appreciably, although a downward trend was observed with risperidone. Given known ethnic differences in adiposity and S(I), we performed secondary analysis in African American and Hispanic subjects. In this subset, olanzapine expanded both total and visceral adiposity (p<0.02); no increase was observed with risperidone. There were modest downward trends for SI with both treatments. By week 24, olanzapine-treated subjects exhibited diminished DI (p=0.033), indicating inadequate pancreatic compensation for insulin resistance. CONCLUSIONS: This is the first prospective study in psychiatric patients that quantified antipsychotic effects on the multiple metabolic processes that increase diabetes risk. Results indicate that ethnic minorities may have greater susceptibility to antipsychotic-induced glucoregulatory complications.

Incidence and costs of polypharmacy: data from a randomized, double-blind, placebo-controlled study of risperidone and quetiapine in patients with schizophrenia or schizoaffective disorder.

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.

Evaluating movement disorders in pediatric patients receiving risperidone: a comparison of spontaneous reports and research criteria for TD.

BACKGROUND: Movement disorders (MD) in children are relatively common and may be associated with medication use. Objective methods (ie rating scales) and specific research criteria may be helpful in identifying MD-related adverse events that would otherwise not be apparent from spontaneous reports. We assessed whether more stringent and rigorous criteria would provide MD rates similar to those derived subjectively from spontaneous reports. METHODS: MDs were assessed in children with disruptive behavior disorders (DBDs) and subaverage intelligence receiving risperidone. Data were from three 1-year, open-label studies in subjects 4-14 years old. Dyskinesia severity was rated by the Extrapyramidal Symptom Rating Scale (ESRS) dyskinesia subscale. Tardive dyskinesia (TD) was defined: mild dyskinesia (scores 2, 3) in two anatomical areas; or moderate dyskinesia (score >or= 4) in one area for >or= 4 weeks in subjects without dyskinesia at baseline (scores 0, 1). RESULTS: The mean (+/- SD) age of subjects was 9.4 +/- 2.4 years, the mean (+/- SD) risperidone dose was 1.6 +/- 0.7 mg/day, and the mean (+/- SD) exposure was 317.8 +/- 104.5 days. ESRS data were available for 668 subjects. Mean ESRS scores were low throughout the study. At baseline, 655 subjects had no dyskinetic symptoms. One subject met predefined TD criteria after a risperidone dose reduction. Symptoms persisted for 4 weeks, resolving with continued treatment and no dosage change. Two different subjects had TD by spontaneous adverse-event reports, with dyskinetic symptoms at 1-2 visits, and symptoms that resolved after treatment discontinuation. Thirteen subjects had dyskinesia at baseline; their mean ESRS dyskinesia scores decreased at endpoint. CONCLUSION: Using objective rating scales and research criteria, low-dose risperidone was associated with low risk of TD and other MDs in children with DBDs in three large 1-year studies. Careful, objective evaluation of emergent MDs during all stages of treatment is essential for identifying treatment-emergent TD.

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.

The efficacy and safety of risperidone in the treatment of psychosis of Alzheimer's disease and mixed dementia: a meta-analysis of 4 placebo-controlled clinical trials.

BACKGROUND: Dementia typically includes behavioral and psychological symptoms of dementia (BPSD) as well as cognitive decline. Psychosis of Alzheimer's disease (AD) is a specific component of AD, characterized by delusions, misidentifications, and hallucinations. METHODS: This study is a meta-analysis of patients with psychosis of AD from four large placebo-controlled clinical trials of risperidone in dementia. Three trials included patients diagnosed with heterogeneous symptoms of BPSD (those with psychosis of AD were included in this analysis), while one trial included only those diagnosed with psychosis of AD. Efficacy was measured using the Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD) Psychosis subscale and Clinical Global Impression (CGI). RESULTS: Primary analyses in the psychosis of AD population demonstrated that risperidone significantly improved scores on the BEHAVE-AD Psychosis subscale and CGI scale compared with placebo. Secondary analyses demonstrated that patients with more severe symptoms showed a more pronounced response to treatment with risperidone compared with placebo than those patients with less severe symptoms. Extrapyramidal symptoms and somnolence were more frequent with risperidone than placebo (p=0.04). Cerebrovascular adverse events and all-cause mortality were observed more frequently, although not statistically significantly, with risperidone versus placebo. CONCLUSIONS: This meta-analysis of psychosis of AD showed improvement in psychotic symptoms and general clinical improvement in patients with psychosis of AD treated with risperidone compared with placebo. The benefits of treatment were most significant in patients with severe symptoms. The safety profile of risperidone in this psychosis of AD population was similar to the more general BPSD population.

Maintenance therapy with once-monthly administration of long-acting injectable risperidone in patients with schizophrenia or schizoaffective disorder: a pilot study of an extended dosing interval.

BACKGROUND: Several clinical studies have established the efficacy, safety, and tolerability of long-acting risperidone administered once every 2 weeks in patients with schizophrenia or schizoaffective disorder. This report evaluates preliminary efficacy, safety, tolerability, and pharmacokinetic data for a novel (once-monthly) administration of long-acting injectable risperidone 50 mg in patients with schizophrenia or schizoaffective disorder. METHODS: Clinically stable patients participated in a 1-year, open-label, single-arm, multicenter pilot study. During the 4-week lead-in phase, patients received long-acting risperidone 50 mg injections every 2 weeks, with 2 weeks of oral risperidone supplementation. Injections of long-acting risperidone 50 mg every 4 weeks followed for up to 48 weeks, without oral supplementation. The primary endpoint was relapse; other assessments included PANSS, CGI-S, adverse event reports, and determination of risperidone and 9-hydroxyrisperidone plasma concentrations. RESULTS: Twelve patients in the intent-to-treat population (n = 67) met relapse criteria (17.9%). Relapse risk at 1 year was estimated as 22.4%. Non-statistically significant improvements in symptoms (PANSS) and clinical status (CGI-S) at endpoint were observed. The most common adverse events included schizophrenia aggravated not otherwise specified (19.5%), anxiety (16.1%), insomnia (16.1%), and headache (11.5%). There were no unexpected safety and tolerability findings. Mean plasma concentrations for risperidone and 9-hydroxyrisperidone were generally stable during the study. CONCLUSION: Once-monthly dosing of long-acting risperidone was well tolerated, associated with a relatively low relapse rate (similar to that reported with other antipsychotics), and maintained the clinically stable baseline status of most patients. Although the results suggest that some symptomatically stable patients with schizophrenia or schizoaffective disorder might be safely managed with long-acting risperidone 50 mg once monthly, these findings alone do not identify which patients will have a sufficient therapeutic benefit nor do they quantify comparative effects of standard and altered dosing. Study limitations (the open-label pilot study design, small sample size, and lack of a concurrent biweekly treatment arm) prevent broad interpretations and extrapolations of results. Controlled studies would be required to support a recommendation for alternative dosing regimens.

Risperidone improves behavioral symptoms in children with autism in a randomized, double-blind, placebo-controlled trial.

Subgroup analysis of children (5-12 years) with autism enrolled in an 8-week, double-blind, placebo-controlled trial of risperidone for pervasive developmental disorders. The primary efficacy measure was the Aberrant Behavior Checklist-Irritability (ABC-I) subscale. Data were available for 55 children given risperidone (n=27) or placebo (n=28); mean baseline ABC-I ( +/- SD) was 20.6 (8.1) and 21.6 (10.2). Risperidone [mean dose ( +/- SD): 1.37 mg/day (0.7)] resulted in significantly greater reduction from baseline to endpoint in ABC-I versus placebo [mean change ( +/- SD): -13.4 (1.5) vs. -7.2 (1.4), P<0.05; ES=-0.7]. The most common adverse effect with risperidone was somnolence (74% vs. 7% with placebo). Risperidone treatment was well tolerated and significantly improved behavioral problems associated with autism.

Patient-based and clinician-based support for the remission criteria in schizophrenia.

This analysis characterizes patients with schizophrenia or schizoaffective disorder treated with risperidone who met remission criteria. In a 50-week, open-label trial, stable patients received long-acting injectable risperidone every 2 weeks. Remission criteria included severity (absent-mild ratings on core symptoms of the Positive and Negative Syndrome Scale) and duration (> or =6 months) components. The patients not remitted (severity component only) at baseline (n=394) are the subjects of this report. Measures applied included the PANSS, Clinical Global Impressions-Severity, patient-rated mental health status (Short Form-36), and Drug Attitude Inventory. Among patients who met remission criteria during the study (n=82), mean scores for all 30 PANSS items reflected absent-mild ratings at endpoint. The highest items represented an 'interpersonal' cluster, although mean ratings were still minimal to mild. Remitted patients experienced substantial improvements in Short Form-36 and Drug Attitude Inventory scores at endpoint. Although improvement occurred, it was less robust in patients who remained nonremitted (n=312). Logistic regression analysis found that remission (severity component only) was associated with a 97.1% probability of a 'not ill' rating on the Clinical Global Impressions-Severity. These remission criteria identified patients who differed from the nonremitted population on symptoms of psychopathology, medication attitude, health status, and overall clinical status, supporting the clinical validity of the remission criteria.

Reduction in psychotic symptoms as a predictor of patient satisfaction with antipsychotic medication in schizophrenia: data from a randomized double-blind trial.

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.

A double-blind comparison of risperidone, quetiapine and placebo in patients with schizophrenia experiencing an acute exacerbation requiring hospitalization.

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.

Post hoc comparison of daily rates of nausea and vomiting with once- and twice-daily galantamine from a double-blind, placebo-controlled, parallel-group, 6-month study.

BACKGROUND: A once-daily extended-release galantamine(GAL-ER) formulation has been designed to improve tolerability compared with twice-daily immediate-release galantamine (GAL-IR). OBJECTIVE: The aim of this study was to conduct a post hoc analysis of the clinical presentation of nausea and vomiting with GAL-ER compared with GAL-IR in subjects with mild to moderate Alzheimer's disease (AD). METHODS: This is the report of a post hoc analysis of a large, randomized, double-blind, placebo-controlled, multicenter trial of GAL-ER with GAL-IR as the active control in subjects with mild to moderate AD. Galantamine dose was titrated every 4 weeks by increments of 8 mg/d to a daily dose of 16 or 24 mg, based on tolerability. Daily rates of nausea and vomiting were compared for the GAL-ER and GAL-IR groups. AUCs of the daily percentage of subjects reporting nausea/vomiting during dose titration were calculated. Antiemetic use for nausea/vomiting was compared between GAL-ER and GAL-IR groups. RESULTS: Demographic characteristics were similar between the GAL-ER, GAL-IR, and placebo groups. Nausea was reported by 16.9% (54/319) of GAL-ER, 13.8% (45/326) of GAL-IR, and 5.0% (16/320) of placebo patients; vomiting was reported for 6.6% (21/319) of GAL-ER, 8.6% (28/326) of GAL-IR, and 2.2% (7/320) of placebo patients. The mean (SD) daily rate of nausea in the total population was 3.1 (13.43%) in the GAL-ER group and 5.2% (22.07%) in the GAL-IR group (P = NS); the mean (SD) daily rate of vomiting for the total population was 0.6% (4.14%) in the GAL-ER group and 1.6% (14.50%) in the GAL-IR group (P = NS). The mean (SD) daily rate of nausea or vomiting in the total population was 1.2 (8.46) and 0.4 (5.44) in the placebo group, respectively. For subjects reporting nausea, the mean (SD, SE) percentage of days with nausea was lower with GAL-ER than with GAL-IR (18.4% [28.22%, 5.31%] vs 38.0% [48.23%, 6.04%]; P = 0.014). AUC of the daily percentage of subjects reporting nausea/vomiting during dose titration was significantly higher in the GAL-IR group compared with the placebo group (320.9 vs 102.9; P = 0.01); there was no statistical difference between the GAL-ER group and placebo (171.1 vs 102.9; P = NS). Antiemetic use by subjects reporting nausea or vomiting was significantly lower in the GAL-ER group than the GAL-IR group (33.3% vs 53.4%; P = 0.028). CONCLUSIONS: In these subjects with AD, the daily percentage of subjects reporting nausea and vomiting, and the percentage of days with vomiting among subjects reporting vomiting, did not significantly differ between the GAL-ER and GAL-IR groups. However, GAL-ER was associated with a significantly lower percentage of days with nausea than GAL-IR among subjects reporting nausea. AUC of the daily percentage of subjects with nausea or vomiting during dose titration did not differ significantly between the GAL-ER and placebo groups but was significantly higher in the GAL-IR group than placebo. Subjects with nausea or vomiting who received GAL-ER reported significantly less antiemetic use than those treated with GAL-IR. These results suggest the need for additional studies to explore the potential differences in the tolerability of these formulations.

Insight and its relationship to clinical outcomes in patients with schizophrenia or schizoaffective disorder receiving long-acting risperidone.

Poor insight is common in schizophrenia, predictive of non-compliance, and an impediment to effective patient management. We hypothesized that long-acting risperidone would be associated with enhanced insight, contributing to improved quality of life measures. In an international, open-label 50-week study, stable patients received long-acting risperidone every 2 weeks. Assessments included the Positive and Negative Syndrome Scale [PANSS; item G12 rated 'impaired insight and judgment' from 1 (no impairment) to 7 (severe impairment)]; Clinical Global Impressions-Severity (CGI-S); and the Medical Outcomes Study Short-form 36-item Health Survey (SF-36) (patient-rated quality of life). Correlation and regression post-hoc analyses examined associations between insight and other measures. At baseline, 314 (51.1%; N=614) patients had impaired insight (G12=3-7) and 83 (26.4%) achieved normal or near normal ratings at endpoint (G12=1-2). Symptom severity corresponded with insight: baseline mean+/-SD PANSS total scores were 56.0+/-14.4 in patients without impaired insight (G12=1-2); 73.4+/-15.7 with mild-moderate impairment (G12=3-4); and 86.0+/-17.4 with severe impairment (G12=5-7). These scores improved significantly in each group at endpoint (P<0.001). Improved insight ratings correlated with improvements in CGI-S (r=0.37); PANSS disorganized thought (r=0.46); negative symptoms (r=0.32); and anxiety/depression (r=0.24; P<0.001 all comparisons), but not quality of life ratings. The change in insight did not contribute significantly to the variance in SF-36 scores; however, changes in negative symptoms, anxiety/depression and CGI-S scores did contribute significantly. Long-acting risperidone was associated with improvements in insight, symptom domains, clinical status and quality of life measures. Associations were noted between patient-rated quality of life and specific symptom domains, but not insight.