quetiapine-fumarate and Cognition-Disorders

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Cognition Disorders; Cytoskeletal Proteins; Dibenzothiazepines; Dopamine; Dopamine Antagonists; Humans; Nerve Tissue Proteins; Olanzapine; Pirenzepine; Proto-Oncogene Proteins c-fos; Quetiapine Fumarate; Receptors, Dopamine D2; Receptors, Serotonin; Risperidone; Schizophrenia; Serotonin Antagonists

The syndrome of schizophrenia often includes negative symptoms and severe cognitive deficits that are resistant to change with conventional pharmacotherapy. The efficacy of clozapine in the reduction of the negative syndrome has prompted a series of studies implicating circumscribed cognitive improvements. Restrictions on the use of clozapine have encouraged the development and introduction of novel compounds with a clinical efficacy profile similar to clozapine that are hoped also to have beneficial cognitive effects. The present review summarizes studies of the cognitive efficacy of novel antipsychotic medications, particularly in regard to issues in experiment design and study implementation that might facilitate additional research. Although preliminary support exists for relatively circumscribed improvement of cognitive status with the use of clozapine and risperidone--and more general improvement with the use of olanzapine--specific inferences relating cognitive change to particular treatments will remain speculative until more sophisticated investigations are completed. The present review emphasises the most relevant design limitations in past studies to provide practical suggestions for the implementation of subsequent investigations Previous results have established the possibility of a medication-based change in cognitive status in schizophrenia Future research will determine the validity of these changes, the cerebral mechanism involved, and their significance to improved prognosis.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Cognition Disorders; Dibenzothiazepines; Humans; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risperidone; Schizophrenia; Severity of Illness Index

The neurocognitive impairment associated with schizophrenia has been well established. Such impairment may be present prior to the onset of the positive symptoms of schizophrenia and persist during periods of remission. Neurocognitive deficits predict multiple domains of outcome; treating such deficits is therefore regarded as highly important. Conventional antipsychotic agents do not appear to favorably affect cognitive function in schizophrenia. Indeed, their propensity to induce adverse effects such as extrapyramidal symptoms may further impair cognitive function. A growing body of evidence suggests that patients taking atypical antipsychotics perform better on some tests of neurocognitive ability than patients receiving conventional agents, with implications for adaptive functioning. The neurocognitive benefits of the atypical antipsychotic agents discussed in this article support their use as a first-line therapy for schizophrenia.

Topics: Adult; Antipsychotic Agents; Cognition Disorders; Dibenzothiazepines; Haloperidol; Humans; Male; Models, Psychological; Neuropsychological Tests; Psychometrics; Quetiapine Fumarate; Reproducibility of Results; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

The advent of the atypical antipsychotics marked a new era in the history of the treatment of psychotic disorders. To evaluate the published literature about the available atypical antipsychotics--clozapine, risperidone, olanzapine, and quetiapine--and select the most appropriate treatment for specific patients, physicians need to understand the outcome measures used in clinical studies, the pharmacologic differences that explain varying side effect profiles, and pharmacoeconomic assessments that are used in the decision-making process. While the atypical antipsychotics have established efficacy in the overall treatment of schizophrenia, they may differ in their effects on factors such as cognitive function, overall quality of life, adverse events, and hospitalization status. Each of these factors should be considered when weighing treatment options for an individual patient.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Cognition Disorders; Cost-Benefit Analysis; Dibenzothiazepines; Drug Approval; Health Care Costs; Health Status; Hospitalization; Humans; Meta-Analysis as Topic; Olanzapine; Outcome Assessment, Health Care; Pirenzepine; Quality of Life; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome; United States; United States Food and Drug Administration

Cognitive deficits are an integral feature of schizophrenia and have a deleterious effect on the ability of schizophrenic patients to work and function in a social environment. Drugs that bring about substantial cognitive improvement represent a major contribution in improving the quality of life in schizophrenia. Recent studies have suggested that the atypical antipsychotics may be more useful than conventional agents for improving cognition. There is evidence that scores on neuropsychological assessments have improved after treatment with clozapine, risperidone, and quetiapine. Future research is needed to characterize and quantify the cognitive effects of the atypical antipsychotics.

Topics: Antipsychotic Agents; Clinical Trials as Topic; Clozapine; Cognition Disorders; Dibenzothiazepines; Humans; Neuropsychological Tests; Quality of Life; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

We previously reported that treatment with 160mg/d of lurasidone improved cognitive performance in a manner superior to placebo, quetiapine XR 600mg/d, and lurasidone 80mg/d, based on a 6-week randomized trial of patients with an acute exacerbation of schizophrenia. The objective of this post-hoc analysis was to explore the cognitive and functional performance of patients whose final doses of lurasidone were 40/80mg/d, 120mg/d, and 160mg/d compared to quetiapine XR 200-800mg/d (QXR) during a 6-month, double-blind continuation study that followed a short-term trial. Subjects who received final doses of lurasidone 120mg/d (n=77) and 160mg/d (n=49) showed significantly greater improvement in overall cognitive performance compared to QXR (n=85) at week 32 (month 6 of the extension study), while those on last doses of 40/80mg/d (n=25) showed a trend towards significance at week 32. Mean changes in neurocognitive composite z-score from pre-treatment baseline were significant for the 3 lurasidone final dose groups at both weeks 19 and 32, with composite change scores of z=1.53, z=1.43, and z=1.34 for the lurasidone 40/80mg/d, 120mg/d, and 160mg/d, respectively, at week 32. In contrast, the composite change score was not statistically significant in the overall quetiapine group (z=0.46), with none of the individual quetiapine doses showing any significant improvement. Functional capacity scores improved in all treatment groups. Our findings indicate improved cognitive performance in patients treated with each of the flexible doses of lurasidone 40-160mg/d, compared to quetiapine XR 200-800mg/d. All doses of lurasidone were superior to all doses of quetiapine for cognitive performance.

Topics: Antipsychotic Agents; Cognition; Cognition Disorders; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Least-Squares Analysis; Lurasidone Hydrochloride; Neuropsychological Tests; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Time Factors; Treatment Outcome

The aim of this analysis was to compare the effects of 2 atypical antipsychotic agents, lurasidone (80 mg/d or 160 mg/d) and quetiapine XR (600 mg/d), on daytime alertness, and to evaluate the effects of daytime sleepiness on treatment outcomes in patients with an acute exacerbation of schizophrenia.. Patients who met Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR) criteria for schizophrenia were randomized to 6 weeks of double-blind treatment with fixed doses of lurasidone 80 mg/d (n = 125), lurasidone 160 mg/d (n = 121), quetiapine XR 600 mg/d (n = 119), or placebo (n = 121), all dosed once daily in the evening, with food. Daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS).. Daytime sleepiness improved in the lurasidone and placebo-treated groups but worsened in the quetiapine XR treatment group when compared to placebo (p = 0.001) and to either dose of lurasidone (both p < 0.01). Sedation associated with quetiapine XR treatment mediated an improvement in agitation [assessed by the Positive and Negative Syndrome Scale-Excitement (PANSS-EC) subscale] and a worsening in functional capacity [assessed by the University of California-San Diego (UCSD) Performance-Based Skills Assessment-Brief Version (UPSA-B) total score]; these mediating relationships were not observed for the lurasidone or placebo treatment groups.. In this 6-week double-blind study, treatment with lurasidone 80 mg or 160 mg, administered once daily in the evening, was associated with a reduction in daytime sleepiness similar in magnitude to placebo, while quetiapine XR 600 mg/d was associated with a significant increase in daytime sleepiness, compared to both lurasidone dose groups and placebo. Daytime sleepiness was associated with improvement in agitation and worsening in functional capacity for quetiapine XR, but not lurasidone or placebo-treated patients.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Cognition Disorders; Dibenzothiazepines; Disorders of Excessive Somnolence; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Isoindoles; Lurasidone Hydrochloride; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Thiazoles; Treatment Outcome; Young Adult

Negative symptoms that do not improve following antipsychotic treatment represent a challenge for development of effective treatments. Few studies have been carried out so far, especially in first-episode schizophrenia patients, to clarify prevalence, correlates and impact of persistent negative symptoms (PNS) on short- and long-term outcome of the disease. All patients from EUFEST study for whom both baseline and 12-month assessments were available were included (N=345). PNS were defined as the presence of at least one negative symptom of moderate or higher severity, not confounded by depression or parkinsonism, at baseline and after 1 year of treatment. Patients with PNS were compared to those with at least one negative symptom of moderate or higher severity at the baseline, not persisting after 1 year, on demographic, clinical, neurocognitive, global functioning and quality of life measures. PNS not confounded by depression or parkinsonism were present in 6.7% of the sample. The symptom that more often persisted was blunted affect. Patients with PNS differed from those without PNS for a longer duration of untreated psychosis (DUP) and a more frequent discontinuation of study treatment; they also had a poorer psychopathological outcome and a worse global functioning after 1 year of treatment. The presence of PNS was associated to poorer improvement of all psychopathological dimensions and worse global functioning after 1 year of treatment. The longer DUP in subjects with PNS suggests that programs aimed at shortening DUP might reduce the prevalence of PNS and improve prognosis of schizophrenia.

Topics: Adolescent; Adult; Amisulpride; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Dibenzothiazepines; Female; Haloperidol; Humans; Male; Neuropsychological Tests; Olanzapine; Piperazines; Psychomotor Disorders; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Sulpiride; Thiazoles; Treatment Outcome; Young Adult

Clozapine, the most widely used option in treatment-resistant schizophrenia, has been shown to be superior to other antipsychotic medications in improving cognitive function in patients. However, the results have not been consistent and the mechanisms underlying this effect have not been elucidated. Thus, the purpose of the present study was to evaluate verbal and nonverbal cognition (using visuospatial processing tests) in patients treated with clozapine (initially treatment resistant) and those treated with other second-generation antipsychotics, relative healthy control subjects. Furthermore, we examined neural correlates of visuospatial processing in the three groups.. Twenty schizophrenia patients treated with clozapine (TR-C group), 23 patients stabilised with atypical antipsychotics other than clozapine (NTR group), and 21 healthy control participants completed a battery of verbal and visuospatial cognitive tests. In addition, participants underwent functional magnetic resonance imaging (fMRI) while performing one of the visuospatial tests (the mental rotation task). The fMRI data were analysed separately in each group using Statistical Parametric Mapping software (SPM5).. Overall, schizophrenia patients exhibited deficit on verbal and nonverbal processing relative to the healthy controls, but we observed some interesting differences between the two groups of patients. Specifically, the NTR group performed better than the TR-C group on the Block Design and the Raven's Progressive Matrices. With respect to brain function during mental rotation, the NTR group showed significant activations in regions of the temporal and occipital cortex, whereas the TR-C patients did not. The relative deactivations associated with the task were also more robust in NTR compared to the other group of patients, despite a similar performance.. Present results suggest better visuospatial processing in the NTR relative to the TR-C group. This difference could be attributed to the treatment resistance itself or a lack of beneficial effect of clozapine relative to other atypical antipsychotics in ameliorating nonverbal abilities. Future studies of the relationship between clozapine and cognition, as well as between treatment resistance and cognition, are warranted.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Cognition; Cognition Disorders; Dibenzothiazepines; Drug Resistance; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Olanzapine; Quetiapine Fumarate; Risperidone; Schizophrenia; Space Perception; Young Adult

Twenty-three adolescents with psychotic disorders, aged from 13 to 18 years, participated in a 12-week open label trial (17 adolescents completed the study) in order to examine the impact of quetiapine on clinical status and cognitive functions (encompassing processing speed, attention, short-term memory, long-term memory and executive function). An improvement in Clinical Global Impression and Positive and Negative Symptom Scale (P's ≤ 0.001) was observed. In addition, after controlling for amelioration of symptoms, a significant improvement was observed on one executive function (P = 0.044; Trail Making Part B). The remaining cognitive abilities showed stability. In addition, we observed an interaction between quetiapine doses (>300 mg/day or <300 mg/day) and time, where lower doses showed more improvement in verbal short-term memory (P = 0.048), inhibition abilities (P = 0.038) and positive symptoms (P = 0.020). The neuropsychological functioning of adolescents with psychotic disorders remained mainly stable after 12 weeks of treatment with quetiapine. However, lower doses seemed to have a better impact on two components of cognition (inhibition abilities and verbal short-term memory) and on positive symptoms.

Topics: Adolescent; Adult; Analysis of Variance; Antipsychotic Agents; Cognition Disorders; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Male; Neuropsychological Tests; Nootropic Agents; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Treatment Outcome

The primary purpose of this study was to compare changes in cognition in early-onset psychosis after 6-months treatment with quetiapine or olanzapine. This is a randomized, single-blind, 6-month study in 50 adolescents with a diagnosis of early-onset psychosis. Patients were randomized to quetiapine (n = 24) or olanzapine (n =26). A thorough neuropsychological battery was administered at baseline and after 6-month treatment. Out of the total sample included in the study, 32 patients completed at least 6-months treatment with the assigned medication (quetiapine, n =16; olanzapine, n = 16). No changes were observed in cognitive performance after 6-month treatment with quetiapine or olanzapine. Although some trends toward cognitive improvement were observed for the olanzapine group after 6-month treatment, neither group showed statistically significant gains. Furthermore, there was no evidence of any differential efficacy of olanzapine or quetiapine on cognitive improvement in this sample of adolescents with psychosis.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cognition Disorders; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Male; Neuropsychological Tests; Olanzapine; Psychometrics; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Single-Blind Method; Spain; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Case-Control Studies; Cognition Disorders; Dibenzothiazepines; Executive Function; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Quetiapine Fumarate; Schizophrenia

The impact of the atypical antipsychotics olanzapine, quetiapine, and risperidone on cognition in patients with Alzheimer's disease is unclear. The authors assessed the effects of time and treatment on neuropsychological functioning during the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease study (CATIE-AD).. CATIE-AD included 421 outpatients with Alzheimer's disease and psychosis or agitated/aggressive behavior who were randomly assigned to receive masked, flexible-dose olanzapine, quetiapine, risperidone, or placebo. Based on their clinicians' judgment, patients could discontinue the originally assigned medication and receive another randomly assigned medication. Patients were followed for 36 weeks, and cognitive assessments were obtained at baseline and at 12, 24, and 36 weeks. Outcomes were compared for 357 patients for whom data were available for at least one cognitive measure at baseline and one follow-up assessment that took place after they had been on their prescribed medication or placebo for at least 2 weeks.. Overall, patients showed steady, significant declines over time in most cognitive areas, including in scores on the Mini-Mental State Examination (MMSE; -2.4 points over 36 weeks) and the cognitive subscale of the Alzheimer's Disease Assessment Scale (-4.4 points). Cognitive function declined more in patients receiving antipsychotics than in those given placebo on multiple cognitive measures, including the MMSE, the cognitive subscale of the Brief Psychiatric Rating Scale, and a cognitive summary score summarizing change on 18 cognitive tests.. In CATIE-AD, atypical antipsychotics were associated with worsening cognitive function at a magnitude consistent with 1 year's deterioration compared with placebo. Further cognitive impairment is an additional risk of treatment with atypical antipsychotics that should be considered when treating patients with Alzheimer's disease.

Topics: Activities of Daily Living; Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Dibenzothiazepines; Disease Progression; Double-Blind Method; Drug Substitution; Female; Follow-Up Studies; Humans; Male; Mental Status Schedule; Neuropsychological Tests; Olanzapine; Patient Dropouts; Quetiapine Fumarate; Risperidone

The study aimed to explore by means of single-trial event-related potentials (ERPs), whether and how the medication change from older neuroleptics to quetiapine in schizophrenic patients led to a significant cognitive enhancement. This single-trial ERP analysis helps to investigate attention and memory processes in the single patient before and after treatment.. Thirteen schizophrenic patients (mean age: 40.1+/-13.5 years) were followed up for 16 weeks and assessed for changes of clinical symptoms and ERP components P300 representing target detection processes and N400 indexing context integration in word recognition processes. Three subjects had to be excluded from the ERP recording sessions because of excessive blink artefacts and movements.. Regarding the P300 components of the target detection, there were significant increases of amplitudes in 5 of 10 patients (50%) at week 16 comparing with week 0. Regarding the N400 components of the word recognition, there were significant increases of amplitudes in 4 of 10 patients (40%) at week 16 comparing with week 0.. The mean scores of PANSS, MADRS, Bf-S, SCL-90 and CGI-S at the end of study (week 16) showed significant improvements compared to the baselines (week 0) (p<0.05). During the study, no extrapyramidal symptoms as well as akathisia were reported after quetiapine treatment. These preliminary data suggest that quetiapine might partially improve the cognitive functions in the context integration and target detection processing in these patients. This technical procedure (single-trial ERP) may help to differentially assess cognitive enhancements in each single patient under treatment.

Topics: Adult; Antipsychotic Agents; Brain; Cognition; Cognition Disorders; Dibenzothiazepines; Electroencephalography; Event-Related Potentials, P300; Evoked Potentials; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neuropsychological Tests; Quetiapine Fumarate; Recognition, Psychology; Schizophrenia; Signal Detection, Psychological; Young Adult

The study measured the effects of atypical antipsychotics on psychiatric and behavioral symptoms in patients with Alzheimer's disease and psychosis or agitated behavior.. The Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) Alzheimer's disease effectiveness study included 421 outpatients with Alzheimer's disease and psychosis or agitated/aggressive behavior. Patients were assigned randomly to masked, flexible-dose treatment with olanzapine, quetiapine, risperidone, or placebo for up to 36 weeks. Patients could be randomly reassigned to a different medication at the clinician's discretion, which ended phase 1. Psychiatric and behavioral symptoms, functioning, cognition, care needs, and quality of life were measured at regular intervals.. In relation to placebo, the last observation in phase 1 showed greater improvement with olanzapine or risperidone on the Neuropsychiatric Inventory total score, risperidone on the Clinical Global Impression of Changes, olanzapine and risperidone on the Brief Psychiatric Rating Scale (BPRS) hostile suspiciousness factor, and risperidone on the BPRS psychosis factor. There was worsening with olanzapine on the BPRS withdrawn depression factor. Among patients continuing phase 1 treatment at 12 weeks, there were no significant differences between antipsychotics and placebo on cognition, functioning, care needs, or quality of life, except for worsened functioning with olanzapine compared to placebo.. In this descriptive analysis of outpatients with Alzheimer's disease in usual care settings, some clinical symptoms improved with atypical antipsychotics. Antipsychotics may be more effective for particular symptoms, such as anger, aggression, and paranoid ideas. They do not appear to improve functioning, care needs, or quality of life.

Topics: Activities of Daily Living; Aged; Aggression; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Brief Psychiatric Rating Scale; Cognition Disorders; Dibenzothiazepines; Female; Humans; Male; Neuropsychological Tests; Olanzapine; Psychomotor Agitation; Psychotic Disorders; Quality of Life; Quetiapine Fumarate; Risperidone; Surveys and Questionnaires

To evaluate predictors of treatment discontinuation against medical advice and poor medication adherence among first-episode patients treated with olanzapine, quetiapine, or risperidone.. First-episode patients with schizophrenia, schizophreniform disorder, or schizoaffective disorder (DSM-IV) were randomly assigned to olanzapine (2.5-20 mg/day), quetiapine (100-800 mg/day), or risperidone (0.5-4 mg/day) as part of a 52-week, randomized, double-blind, flexible-dose, multicenter study. Patients were enrolled from 2002 to 2004 at one of 26 sites in the United States and Canada. Survival analysis tested for predictors of treatment discontinuation against medical advice, while mixed models tested for predictors of poor medication adherence. Significant findings from the final models were replicated in sensitivity analyses.. Of the 400 patients randomly assigned to treatment, 115 patients who discontinued treatment against medical advice and 119 study completers were compared in this analysis. Poor treatment response (p < .001) and low medication adherence (p = .02) were independent predictors of discontinuation against medical advice. Ongoing substance abuse, ongoing depression, and treatment response failure significantly predicted poor medication adherence (p < .01). Higher cognitive performance at baseline and ethnicity (black) were also associated with lower medication adherence (p < .05). An association between poor medication adherence and illness insight at study entry was found at trend level (p = .059).. This study highlights the importance of treatment response in predicting discontinuation against medical advice and poor adherence to medication in first-episode patients. These results also support interventions to improve adherence behavior, particularly by targeting substance use disorders and depressive symptoms.. ClinicalTrials.gov identifier NCT00034892 (http://www.clinicaltrials.gov).

Topics: Adult; Antipsychotic Agents; Attitude to Health; Benzodiazepines; Cognition Disorders; Culture; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Olanzapine; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Surveys and Questionnaires; Treatment Refusal

In recent years, growing evidence supports the efficacy of antipsychotic addition to serotonin reuptake inhibitors in patients with treatment-refractory obsessive-compulsive disorder. This study is the first to investigate the effects of antipsychotic addition on cognitive functioning in obsessive-compulsive disorder patients. Cognitive functioning was evaluated at baseline and at endpoint of an 8-week double-blind, placebo-controlled quetiapine addition trial. Neurocognitive performance was compared between the placebo and quetiapine group and between responders and nonresponders. The neuropsychological test battery consisted of the national adult reading test, the Wisconsin Card Sorting Test, the Trail Making Test, verbal fluency, the Stroop Color Word Test, the California Verbal Learning Test, the Rey Complex Figure Task, the Continuous Performance Test, and the Digit Symbol Substitution. The results of this study suggest that quetiapine addition to serotonin reuptake inhibitors has no major effects on cognitive functioning in obsessive-compulsive disorder patients, apart from some evidence for a failure to maintain set on the Wisconsin Card Sorting Test. It is proposed that this failure may be caused by attention difficulties owing to somnolence.

Topics: Adult; Antipsychotic Agents; Attention; Cognition; Cognition Disorders; Color Perception; Dibenzothiazepines; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Memory; Middle Aged; Obsessive-Compulsive Disorder; Psychomotor Performance; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors; Treatment Outcome; Verbal Behavior

Neurocognitive impairment in schizophrenia is severe and is an important predictor of functional outcome. The relative effect of the second-generation (atypical) antipsychotic drugs and older agents on neurocognition has not been comprehensively determined.. To compare the neurocognitive effects of several second-generation antipsychotics and a first-generation antipsychotic, perphenazine.. Randomized, double-blind study of patients with schizophrenia assigned to receive treatment with olanzapine, perphenazine, quetiapine fumarate, or risperidone for up to 18 months as reported previously by Lieberman et al. Ziprasidone hydrochloride was included after its approval by the Food and Drug Administration.. Fifty-seven sites participated, including academic sites and treatment mental health facilities representative of the community.. From a cohort of 1460 patients in the treatment study, 817 completed neurocognitive testing immediately prior to randomization and then after 2 months of treatment.. The primary outcome was change in a neurocognitive composite score after 2 months of treatment. Secondary outcomes included neurocognitive composite score change at 6 months and 18 months after continued treatment and changes in neurocognitive domains.. At 2 months, treatment resulted in small neurocognitive improvements of z = 0.13 for olanzapine (P<.002), 0.25 for perphenazine (P<.001), 0.18 for quetiapine (P<.001), 0.26 for risperidone (P<.001), and 0.12 for ziprasidone (P<.06), with no significant differences between groups. Results at 6 months were similar. After 18 months of treatment, neurocognitive improvement was greater in the perphenazine group than in the olanzapine and risperidone groups. Neurocognitive improvement predicted longer time to treatment discontinuation, independently from symptom improvement, in patients treated with quetiapine or ziprasidone.. After 2 months of antipsychotic treatment, all groups had a small but significant improvement in neurocognition. There were no differences between any pair of agents, including the typical drug perphenazine. These results differ from the majority of previous studies, and the possible reasons are discussed.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Cohort Studies; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Neuropsychological Tests; Olanzapine; Perphenazine; Piperazines; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Thiazoles; Treatment Outcome

The authors sought to compare the effects of olanzapine, quetiapine, and risperidone on neurocognitive function in patients with early psychosis.. In a 52-week double-blind, multicenter study, 400 patients early in the course of psychotic illness (<5 years) were randomly assigned to treatment with olanzapine (2.5-20 mg/day), quetiapine (100-800 mg/day), or risperidone (0.5-4 mg/day). The mean modal daily dose was 11.7 mg (SD=5.3) for olanzapine, 506 mg (SD=215) for quetiapine, and 2.4 mg (SD=1.0) for risperidone. A total of 224 patients completed neurocognitive assessments at baseline and at 12 weeks, and 81 patients also completed them at 52 weeks. Neurocognitive composite scores were calculated from the neurocognitive battery used in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and from the Brief Assessment of Cognition in Schizophrenia.. At week 12, there was significant improvement in neurocognition for each treatment (p<0.01), but no significant overall difference between treatments. Composite z score improvements on the CATIE neurocognitive battery were 0.17 for olanzapine, 0.33 for quetiapine, and 0.32 for risperidone. Composite z score improvements on the Brief Assessment of Cognition in Schizophrenia were 0.19 for olanzapine, 0.34 for quetiapine, and 0.22 for risperidone. Statistically significant relationships between improvements in neurocognition and functional outcome were observed at weeks 12 and 52.. Olanzapine, quetiapine, and risperidone all produced significant improvements in neurocognition in early-psychosis patients. Although cognitive improvements were modest, their clinical importance was suggested by relationships with improvements in functional outcome.

Topics: Adult; Antipsychotic Agents; Attitude to Health; Benzodiazepines; Cognition Disorders; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Health Status; Humans; Least-Squares Analysis; Male; Neuropsychological Tests; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Quality of Life; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Social Adjustment; Treatment Outcome

Neurocognitive impairment is a core feature in the pathology of schizophrenia and considered to be relatively persistent towards psychopharmacological interventions. There are hints that atypical antipsychotics can influence neurocognitive dysfunctions more favorable than conventional compounds. But little is known about differences in efficacy on neurocognitive dysfunctions linked to the variety of receptor profiles of different atypical antipsychotics. This study compared the effects of the atypical antipsychotics quetiapine and olanzapine on cognitive function in patients with an acute episode of schizophrenia. Patients were randomized to receive quetiapine or olanzapine for 8 weeks. Cognitive function was assessed at baseline, week 4 and week 8. Efficacy was assessed weekly using the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Improvement Scale (CGI). Tolerability was assessed each week using the Extrapyramidal Symptom Rating Scale (ESRS), the Barnes Akathisia Scale (BAS) and the Udvalg for Kliniske Undersogelser Side Effect Rating Scale (UKU). In total, 52 patients were enrolled in the study. Data from the 33 patients who completed cognitive assessments at two or more time points out of three (baseline, Week 4 and Week 8) are analyzed here. Both quetiapine and olanzapine improved global cognitive index z-scores, however, this was more marked with quetiapine. Between-group comparisons showed significantly greater improvements in reaction quality/attention with quetiapine than olanzapine. Quetiapine and olanzapine produced significant improvements from baseline to week 8 in PANSS total and subscale scores. Both treatments were well tolerated, especially no EPS occurred during 8 weeks of treatment. Both quetiapine and olanzapine improved cognition; however, the improvement in cognitive index scores was more marked in patients receiving quetiapine. Furthermore, quetiapine produced a significantly greater improvement in reaction quality/attention than olanzapine.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Dibenzothiazepines; Double-Blind Method; Drug Evaluation; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Olanzapine; Quetiapine Fumarate; Schizophrenia; Statistics, Nonparametric

Antipsychotic medications differ in their sedative potential, which can affect cognitive performance. The primary objective of this double-blind study was to compare the effects of treatment initiation with risperidone and quetiapine on cognitive function in subjects with stable bipolar disorder.. Subjects had a DSM-IV diagnosis of bipolar I disorder in partial or full remission and a Young Mania Rating Scale score

Topics: Adult; Antipsychotic Agents; Attention; Bipolar Disorder; Cognition; Cognition Disorders; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Male; Memory; Middle Aged; Quetiapine Fumarate; Reaction Time; Risperidone; Sleep Stages; Sleep Wake Disorders

Topics: Alzheimer Disease; Cholinesterase Inhibitors; Cognition Disorders; Dibenzothiazepines; Disease Progression; Double-Blind Method; Humans; Phenylcarbamates; Psychomotor Agitation; Quetiapine Fumarate; Rivastigmine

To compare the efficacy and tolerability of quetiapine and risperidone in the treatment of schizophrenia.. In this 8-week, double-blind, multicenter, flexible-dose study, patients with schizophrenia (DSM-IV diagnosis) were randomly assigned to quetiapine (200-800 mg/day) or risperidone (2-8 mg/day). The primary hypothesis was that quetiapine was not inferior to risperidone. The primary efficacy measure was change from baseline in Positive and Negative Syndrome Scale (PANSS) total scores; secondary outcomes included response rate (> or = 40% reduction in PANSS scores), Clinical Global Impression-Change (CGI-C), and cognitive and social functioning. Tolerability assessments included treatment-emergent adverse events and changes in weight, glucose, and prolactin. Patients were recruited from June 2001 to September 2002.. Patients (N = 673) were randomly assigned to quetiapine (N = 338, mean dose = 525 mg/day) or risperidone (N = 335, mean dose = 5.2 mg/day). The primary analysis demonstrated noninferiority between treatments (p < .05). Improvements with both treatments were comparable on PANSS total, negative, and general psychopathology subscales. Risperidone-treated patients had a significantly (p = .03) greater improvement in PANSS positive subscale score among all patients, but not among completers. Improvements in PANSS response rates, CGI-C, and cognitive function were similar between treatment groups. Changes in serum glucose and weight were minimal and comparable. The rate of extrapyramidal symptom (EPS)-related adverse events was significantly higher with risperidone (22%) than quetiapine (13%; p < .01). Somnolence was more common with quetiapine (26%) than risperidone (20%; p = .04). Prolactin levels increased with risperidone (+35.5 ng/mL), but decreased with quetiapine (-11.5 ng/mL; p < .001).. Quetiapine and risperidone had broadly comparable clinical efficacy. Both agents improved cognitive and social functioning, and neither had a clinically significant effect on weight or glucose. Somnolence was more common with quetiapine; EPS and elevated prolactin rates were significantly higher with risperidone.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Cognition Disorders; Dibenzothiazepines; Disorders of Excessive Somnolence; Double-Blind Method; Drug Administration Schedule; Female; Humans; Hyperprolactinemia; Male; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

While neuropsychological test performance is correlated with social outcomes in patients with schizophrenia, there is little evidence to date that changes in neuropsychological performance are associated with changes in these outcomes. As part of an efficacy and tolerability study of atypical antipsychotics, the authors used a performance-based measure of social competence as a short-term outcome measure and examined the correlations between changes in social competence and improvements on neuropsychological tests.. Patients with schizophrenia were randomly assigned in a 1:1 ratio to receive treatment with either quetiapine (dose range: 200-800 mg/day) or risperidone (dose range: 2-8 mg/day) for an 8-week period.. Of 673 patients initially randomized, 289 had baseline and endpoint neuropsychological and functional competence data. Scores on the performance-based measure of social competence significantly improved with both treatments, as did a number of aspects of neuropsychological performance. Improvements in several aspects of neuropsychological performance were correlated with the extent of improvement in social competence. There were no overall differences between the treatments in their impact on social competence and neuropsychological performance.. Short-term treatment with both quetiapine and risperidone resulted in improvements in social competence, with these improvements associated with improvements on some of the neuropsychological measures. In addition to their clinical importance, these results support the use of performance-based competence assessments as outcome measures in clinical trials.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Cognition Disorders; Dibenzothiazepines; Double-Blind Method; Emotions; Facial Expression; Female; Humans; Interpersonal Relations; Male; Middle Aged; Neuropsychological Tests; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Social Adjustment; Social Perception; Time Factors; Treatment Outcome

To determine the respective efficacy of quetiapine and rivastigmine for agitation in people with dementia in institutional care and to evaluate these treatments with respect to change in cognitive performance.. Randomised double blind (clinician, patient, outcomes assessor) placebo controlled trial.. Care facilities in the north east of England.. 93 patients with Alzheimer's disease, dementia, and clinically significant agitation.. Atypical antipsychotic (quetiapine), cholinesterase inhibitor (rivastigmine), or placebo (double dummy).. Agitation (Cohen-Mansfield agitation inventory) and cognition (severe impairment battery) at baseline and at six weeks and 26 weeks. The primary outcome was agitation inventory at six weeks.. 31 patients were randomised to each group, and 80 (86%) started treatment (25 rivastigmine, 26 quetiapine, 29 placebo), of whom 71 (89%) tolerated the maximum protocol dose (22 rivastigmine, 23 quetiapine, 26 placebo). Compared with placebo, neither group showed significant differences in improvement on the agitation inventory either at six weeks or 26 weeks. Fifty six patients scored > 10 on the severe impairment battery at baseline, 46 (82%) of whom were included in the analysis at six week follow up (14 rivastigmine, 14 quetiapine, 18 placebo). For quetiapine the change in severe impairment battery score from baseline was estimated as an average of -14.6 points (95% confidence interval -25.3 to -4.0) lower (that is, worse) than in the placebo group at six weeks (P = 0.009) and -15.4 points (-27.0 to -3.8) lower at 26 weeks (P = 0.01). The corresponding changes with rivastigmine were -3.5 points (-13.1 to 6.2) lower at six weeks (P = 0.5) and -7.5 points (-21.0 to 6.0) lower at 26 weeks (P = 0.3).. Neither quetiapine nor rivastigmine are effective in the treatment of agitation in people with dementia in institutional care. Compared with placebo, quetiapine is associated with significantly greater cognitive decline.

Topics: Aged; Alzheimer Disease; Antipsychotic Agents; Cholinesterase Inhibitors; Cognition Disorders; Dibenzothiazepines; Double-Blind Method; Humans; Middle Aged; Phenylcarbamates; Psychomotor Agitation; Quetiapine Fumarate; Rivastigmine; Treatment Failure

To examine the effectiveness of quetiapine versus conventional antipsychotics in improving cognitive and functional outcomes.. Forty stable outpatients with DSM-IV schizophrenia treated in public outpatient clinics were randomly assigned to continue taking conventional antipsychotic medications or switch to quetiapine for 6 months, beginning September 1998 and ending July 2000. Neurocognitive and functional measures were obtained at study entry, 3 months, and 6 months by raters blinded to treatment. Group differences were examined using repeated-measures analyses of covariance for mixed models.. The mean (SD) dose of conventional antipsychotics in chlorpromazine equivalents was 348.00 (348.28) mg/day; the mean (SD) dose of quetiapine was 319.25 (142.55) mg/day. A cognitive function summary score improved in the quetiapine group relative to the group treated with conventional antipsychotics over the 6-month period (F = 5.80, df = 1,28.9; p <.023). Patients taking quetiapine did better with respect to both verbal fluency (initiation) and verbal memory. There were also statistically significant group differences with respect to quality of life favoring the quetiapine group (F = 4.87, df = 1,29; p <.04). Differences were not found with respect to adaptive functioning.. Quetiapine improved cognition relative to conventional agents. After 6 months, groups differed by more than 1 standard deviation when baseline cognitive functioning was taken into account. No group differences were found with respect to improvements in community functioning. Improvements in adaptive functioning may lag behind improvements in cognition. Psychosocial programming may be necessary to translate gains in cognition into improvements in adaptive functioning.

Topics: Adult; Antipsychotic Agents; Cognition Disorders; Cross-Over Studies; Dibenzothiazepines; Female; Humans; Male; Neuropsychological Tests; Psychiatric Status Rating Scales; Quality of Life; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Single-Blind Method; Social Adjustment; Treatment Outcome

Recent evidence suggests that schizophrenia patients taking atypical antipsychotic medications may perform better on some tests of cognitive function than those treated with older antipsychotics. The current study compared the effects of quetiapine and haloperidol on measures of executive function, memory and attention. Subjects were 58 stable outpatients with schizophrenia (DSM III-R) who received a battery of cognitive tests as part of a randomized, double-blind, multi-site clinical efficacy study conducted by AstraZeneca Pharmaceuticals. Cognitive assessments were conducted prior to randomization when patients were receiving < or =30 mg haloperidol or equivalent (mean: 9.2mg/day haloperidol equivalents), and again after 24 weeks of fixed-dose treatment with either quetiapine 600 or 300 mg/day or haloperidol 12 mg/day. Analyses of covariance with planned comparisons were used to compare scores on cognitive measures at the end of 24 weeks by treatment group with baseline cognitive function scores used as covariates. Patients receiving quetiapine 600 mg/day improved to a greater extent than patients receiving haloperidol on overall cognitive function (p<0.02). Specific differences were found for executive function (Verbal Fluency Test, p<0.04), attention (Stroop Color Word Test, p<.03) and verbal memory (Paragraph Recall Test, p<0.02). Treatment group differences were not solely due to benztropine use, medication side effects, or changes in symptomatology. Treatment with quetiapine at higher doses (600 mg/day) relative to haloperidol appears to have a positive impact on important domains of cognitive performance that have been found to predict role function and community outcomes in patients with schizophrenia.

Topics: Antipsychotic Agents; Cognition Disorders; Dibenzothiazepines; Female; Haloperidol; Humans; Male; Neuropsychological Tests; Quetiapine Fumarate; Schizophrenia; Severity of Illness Index

To assess the efficacy of quetiapine, a recently introduced second generation antipsychotic medication, in reducing cognitive impairment in patients with schizophrenia.. Prospective, randomized, double-blind clinical trial.. 25 patients who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, (DSM-IV) criteria for schizophrenia were recruited from 3 Canadian hospitals.. After a 48-hour washout period, 25 patients with schizophrenia were randomly assigned to double-blind treatment with quetiapine or haloperidol for 6 months and evaluated with rating scales for psychotic symptoms, mood and extrapyramidal side effects, as well as standardized neuropsychological measures sensitive to 6 cognitive domains: fine motor skill, attention span, verbal reasoning and fluency, visuospatial construction and fluency, executive skills and visuomotor tracking, and immediate recall of verbal and nonverbal materials. The measures were repeated 8 weeks and 6 months after treatment was initiated.. Quetiapine improved psychosis and mood without inducing extrapyramidal symptoms. Quetiapine also had beneficial effects on cognitive skills, particularly verbal reasoning and fluency skills and immediate recall, with additional improvements on executive skills and visuomotor tracking and on the average of the 6 cognitive domains with sustained treatment. Patients taking haloperidol showed improvements in general clinical status, but no specific improvements on the positive syndrome, the negative syndrome, depression ratings or cognitive skills.. These preliminary results support the potential value of quetiapine for improving cognitive impairment in patients with schizophrenia and emphasize the importance of further research with this promising atypical antipsychotic.

Topics: Adult; Antipsychotic Agents; Cognition Disorders; Decision Making; Dibenzothiazepines; Double-Blind Method; Female; Haloperidol; Humans; Male; Neuropsychological Tests; Prospective Studies; Quetiapine Fumarate; Schizophrenia; Severity of Illness Index; Treatment Outcome

This study aims to identify neuropsychiatric manifestations in neurological Wilson disease (NWD), and their correlation with MRI changes and glutamate excitotoxicity. Forty-three consecutive patients with NWD from a tertiary care teaching hospital were evaluated prospectively who fulfilled the inclusion criteria. The neuropsychiatric evaluation was done using Neuropsychiatric Inventory (NPI) battery that assesses 12 domains including delusion, hallucination, agitation/aggression, dysphoria/depression, anxiety, euphoria, apathy, disinhibition, irritability, aberrant motor activity, appetite change, and abnormal nighttime behavior. Cranial MRI was done using a 3 T machine, and locations of signal changes were noted including the total number of MRI lesions. Serum glutamate level was measured by a fluorescence microplate reader. Abnormal NPI in various domains and total NPI scores were correlated with MRI lesions, serum and urinary copper, and glutamate level. The median age of the patients was 16 years. Forty-one (48.8%) patients had cognitive impairment and 37 (86%) had movement disorder. Neurobehavioral abnormality was detected in all-commonest being agitation (90.7%) followed by appetite change (81.4%), elation (74.4%), irritability (69.8%), anxiety (67.4%), depression (65.1%), apathy (44.2%), night time abnormal behavior (32.6%), aberrant motor behavior (20.9%), delusions (16.3%), and hallucination (18.6%). The thalamic lesion was associated with depression, globus pallidus with depression and anxiety, caudate with anxiety and agitation, brainstem with irritability, and frontal cortex with apathy. Serum glutamate level was higher in NWD. NPI sum score correlated with MRI load and glutamate level. Varying severity of neurobehavioral abnormalities are common in the patients with NWD and correlate with the location of MRI lesion and glutamate level.

Topics: Adolescent; Adult; Behavioral Symptoms; Brain Mapping; Cognition Disorders; Copper; Feeding and Eating Disorders; Female; Glutamic Acid; Hallucinations; Hepatolenticular Degeneration; Humans; Liver; Magnetic Resonance Imaging; Male; Mood Disorders; Movement Disorders; Neuroimaging; Neurotransmitter Agents; Quetiapine Fumarate; Severity of Illness Index; Young Adult

Diabetic patients are at increased risk for developing memory and cognitive deficit. Prior studies indicate that neuroinflammation might be one important underlying mechanism responsible for this deficit. Quetiapine (QTP) reportedly exerts a significant neuroprotective effect in animal and human studies. Here, we investigated whether QTP could prevent memory deterioration and cognitive impairment in a streptozotocin- (STZ-) induced diabetic mouse model. In this study, we found that STZ significantly compromised the behavioral performance of mice in a puzzle box test, but administering QTP effectively attenuated this behavioral deficit. Moreover, our results showed that QTP could significantly inhibit the activation of astrocytes and microglia in these diabetic mice and reduce the generation and release of two cytokines, tumor necrosis factor-

Topics: Animals; Astrocytes; Chemokine CCL2; Cognition Disorders; Cognitive Dysfunction; Diabetes Mellitus, Experimental; Disease Models, Animal; Executive Function; Male; Memory; Mice; Mice, Inbred C57BL; Microglia; Neuroprotective Agents; Quetiapine Fumarate; Streptozocin; Tumor Necrosis Factor-alpha

Reports on prenatal exposure to some of the first generation antipsychotic drugs like, haloperidol, their effects on fetal neurotoxicity and functional impairments in the offspring, are well documented. But studies on in utero exposure to second generation antipsychotics, especially quetiapine, and its effects on fetal neurotoxicity, apoptotic neurodegeneration, postnatal developmental delay and neurobehavioral consequences are lacking. Therefore, the present study was undertaken to evaluate the effect of prenatal administration to equivalent therapeutic doses of quetiapine on neuro-architectural abnormalities, neurohistopathological changes, apoptotic neurodegeneration in fetal hippocampus, and postnatal development and growth as well as its long-lasting imprint on cognitive impairment in young-adult offspring. Pregnant Wistar rats (n=24) were exposed to selected doses (55 mg, 80 mg and 100mg/kg) of quetiapine, equivalent to human therapeutic doses, from gestation day 6 to 21 orally with control subjects. Half of the pregnant subjects of each group were sacrificed at gestation day 21 for histopathological, confocal and electron microscopic studies and rest of the dams were allowed to deliver naturally. Their pups were reared postnatally up to 10 weeks of age for neurobehavioral observations. In quetiapine treated groups, there was significant alterations in total and differential thickness of three typical layers of hippocampus associated with neuronal cells deficit and enhanced apoptotic neurodegeneration in the CA1 area of fetal hippocampus. Prenatally drug treated rat offspring displayed post-natal developmental delay till postnatal day 70, and these young-adult rats displayed cognitive impairment in Morris water maze and passive avoidance regimes as long-lasting impact of the drug. Therefore, quetiapine should be used with cautions considering its developmental neurotoxicological and neurobehavioral potential in animal model, rat.

Topics: Analysis of Variance; Animals; Antipsychotic Agents; Apoptosis; Avoidance Learning; Cognition Disorders; Dose-Response Relationship, Drug; Female; Hippocampus; Male; Maze Learning; Microscopy, Electron; Neurodegenerative Diseases; Pregnancy; Prenatal Exposure Delayed Effects; Quetiapine Fumarate; Rats; Rats, Wistar

Developmental delay, cognitive impairment, and refractory epilepsy are the most frequent consequences found in patients suffering from malformations of cortical development (MCD). However, therapeutic options for these psychiatric and neurological comorbidities are currently limited. The development of white matter undergoes dramatic changes during postnatal brain maturation, thus myelination deficits resulting from MCD contribute to its comorbid diseases. Consequently, drugs specifically targeting white matter are a promising therapeutic option for the treatment of MCD. We have used an in utero irradiation rat model of MCD to investigate the effects of postnatal quetiapine treatment on brain myelination as well as neuropsychological and cognitive performances and seizure susceptibility. Fatally irradiated rats were treated with quetiapine (10mg/kg, i.p.) or saline once daily from postnatal day 0 (P0) to P30. We found that postnatal administration of quetiapine attenuated object recognition memory impairment and improved long-term spatial memory in the irradiated rats. Quetiapine treatment also reduced the susceptibility and severity of pentylenetetrazol-induced seizures. Importantly, quetiapine treatment resulted in an inhibition of irradiation-induced myelin breakdown in the cerebral cortex and corpus callosum. These findings suggest that quetiapine may have beneficial, postnatal effects in the irradiated rats, strongly suggesting that improving MCD-derived white matter pathology is a possible underlying mechanism. Collectively, these results indicate that brain myelination represents an encouraging pharmacological target to improve the prognosis of patients with MCD.

Topics: Animals; Animals, Newborn; Anticonvulsants; Cerebral Cortex; Cognition Disorders; Corpus Callosum; Disease Models, Animal; Malformations of Cortical Development; Maze Learning; Myelin Sheath; Nootropic Agents; Pentylenetetrazole; Quetiapine Fumarate; Rats, Sprague-Dawley; Recognition, Psychology; Seizures; Severity of Illness Index; Spatial Memory; X-Rays

Stress is any condition that seriously affects the balance of the organism physiologically and psychologically. Stress activates the hypothalamic-pituitary-adrenal (HPA) releasing glucocorticoid hormones that produce generalized effects on different body systems including the nervous system. This study aimed to investigate the effect of acute restraint stress (ARS) on cognitive performance by measuring spatial working memory in Y-maze, behavior (anxiety and exploratory behavior) in open field test, expression of synaptophysin and glial fibrillary acidic protein (GFAP) in the hippocampus by immunohistochemistry, dopaminergic receptors (D2) in the basal ganglia by gene expression and comparing the effect of ghrelin and quetiapine on the previous parameters. 36 adult male albino rats constituted the animal model of this work and have been divided into six groups: control group, control group exposed to ARS, quetiapine group, quetiapine group exposed to ARS, ghrelin group and ghrelin group exposed to ARS. We demonstrated more neuroprotective effect for quetiapine compared to ghrelin on stress response, anxiety behavior and working spatial memory impairment due to ARS.

Topics: Analysis of Variance; Animals; Antipsychotic Agents; Cognition Disorders; Dibenzothiazepines; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Exploratory Behavior; Gene Expression Regulation; Ghrelin; Glial Fibrillary Acidic Protein; Hydrocortisone; Male; Maze Learning; Quetiapine Fumarate; Rats; Receptors, Dopamine D2; Stress, Psychological

Topics: Adult; Antimanic Agents; Bipolar Disorder; China; Cognition Disorders; Cross-Sectional Studies; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Lithium Compounds; Male; Quetiapine Fumarate; Valproic Acid; Young Adult

The antidepressant action of quetiapine has been demonstrated in clinical and preclinical studies. Nevertheless, little is known about its effectiveness in the treatment of frontal-like cognitive disturbances that may be associated with stress-related disorder. Therefore, the aim of the present study was to investigate whether quetiapine would prevent and/or reverse stress-induced cognitive impairments in a rat model of prefrontal cortex (PFC)-dependent attentional set-shifting task (ASST). Because quetiapine augmentation to selective serotonin reuptake inhibitors (SSRIs) has recently been proven to be beneficial in neuropsychiatric disorders, a separate experiment was designed to assess the impact of combined administration of inactive doses of quetiapine and escitalopram on ASST performance in rats. According to our previous studies, 1 h daily exposure to restraint stress for 7 days significantly and specifically impaired extra-dimensional (ED) set-shifting ability of rats. Quetiapine (2.5 mg/kg, PO) given to rats prior to the restraint sessions completely prevented this stress-induced cognitive inflexibility. Similar effect was demonstrated after pretreatment with the α1-adrenoceptor antagonist, prazosin (1 mg/kg, IP). Moreover, acute administration of quetiapine before the test reversed set-shifting deficits in stressed rats (0.63, 1.25 and 2.5 mg/kg, PO) and improved ED performance of cognitively unimpaired control animals (1.25 and 2.5 mg/kg, PO). Finally, the combined administration of inactive doses of quetiapine (0.63 and 0.3 mg/kg in control and stressed rats, respectively) and escitalopram (0.3 mg/kg, IP) facilitated set-shifting performance in either control or stressed rats. In conclusion, quetiapine administration either prevented or reversed stress-induced cognitive inflexibility in rats. In addition to promoting of set-shifting by itself, quetiapine also enhanced the procognitive efficacy of escitalopram. The potential contribution of the antagonism at α1-adrenoceptors to the mechanisms underlying the protective action of quetiapine requires further evaluation. These findings may have therapeutic implications for the treatment of frontal-like disturbances, particularly cognitive inflexibility, in stress-related psychiatric disorders. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

Topics: Adrenergic alpha-1 Receptor Antagonists; Animals; Antidepressive Agents, Second-Generation; Behavior, Animal; Citalopram; Cognition Disorders; Dibenzothiazepines; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Male; Neurons; Nootropic Agents; Performance-Enhancing Substances; Prefrontal Cortex; Quetiapine Fumarate; Rats; Rats, Sprague-Dawley; Restraint, Physical; Selective Serotonin Reuptake Inhibitors; Stress, Physiological; Stress, Psychological

Prefrontal cortical dysfunctions, including an impaired ability to shift perceptual attentional set, are core features of schizophrenia. Nevertheless, the effectiveness of second-generation antipsychotic drugs in treating specific prefrontal dysfunctions remains equivocal.. To model schizophrenia-like cognitive inflexibility in rats, we evaluated the effects of repeated administration of ketamine, the noncompetitive antagonist of the N-methyl-D: -aspartate receptor, after a washout period of 14 days in the attentional set-shifting task (ASST). Next, we investigated whether the atypical antipsychotics quetiapine and sertindole would alleviate the ketamine-induced set-shifting impairment.. Ketamine (30 mg/kg) was administered intraperitoneally to rats once daily for 5 or 10 consecutive days to assess its efficacy in producing cognitive impairment. The ASST was performed 14 days following the final drug administration. Quetiapine (0.63, 1.25 or 2.5 mg/kg) or sertindole (2.5 mg/kg) was administered per os 120 min before testing.. The results of the present study demonstrate that ketamine treatment for 10 but not 5 days significantly and specifically impaired rats' performance in the extra-dimensional shift (EDs) stage of the ASST. This cognitive inflexibility was reversed by acute administration of sertindole or quetiapine. Quetiapine also promoted set-shifting in cognitively unimpaired control animals.. The data presented here show that subchronic administration of ketamine induces cognitive inflexibility after a washout period. This cognitive deficit likely reflects clinically relevant aspects of cognitive dysfunction encountered in schizophrenic patients. The beneficial effects of quetiapine on set-shifting may have therapeutic implications for the treatment of schizophrenia and other disorders associated with frontal-dependent cognitive impairments.

Topics: Animals; Antipsychotic Agents; Attention; Cognition Disorders; Dibenzothiazepines; Disease Models, Animal; Dose-Response Relationship, Drug; Excitatory Amino Acid Antagonists; Imidazoles; Indoles; Ketamine; Male; Quetiapine Fumarate; Rats; Rats, Sprague-Dawley; Schizophrenia

Effects of quetiapine on cognition were assessed in a group of first-episode antipsychotic-naïve patients with schizophrenia (N=24). A comprehensive battery of neuropsychological tests was administered at baseline and after 6 months of treatment with quetiapine. In order to examine retest effects, a matched healthy control group (N=24) was also tested at baseline and after 6 months. Only few differential changes were observed between patients and healthy controls. Of 8 cognitive domains examined, only significant changes in executive function suggested possible ameliorating effects of quetiapine. Patients also improved on speed of processing; however, this was parallel to the retest effects found in healthy controls. When covaried for differences at baseline, patients showed smaller improvements in speed of processing than the retest effects found in controls, as well as a lack of retest effects on sustained attention and working memory that were found in healthy controls. The main result of the study is that there was very little evidence of efficacy of quetiapine on cognition. The study also indicated a lack of normal retest effects in patients compared to controls.

Topics: Adolescent; Adult; Analysis of Variance; Antipsychotic Agents; Case-Control Studies; Cognition Disorders; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Psychiatric Status Rating Scales; Quetiapine Fumarate; Retrospective Studies; Schizophrenia; Young Adult

Combination therapy with valproic acid plus quetiapine is recommended as one of the first-line approaches to treatment of manic or mixed episodes in patients with bipolar disorder.. A 66-year-old patient with this psychiatric disease developed parkinsonism and cognitive decline during concomitant treatment with both drugs. The rapid onset of symptoms soon after use of the combination suggested an interaction/using the Karch-Lasagna criteria, the interaction was judged to be definite.. Their evidence on a pharmacokinetic drug interaction between the two drugs is conflicting but possible underlying mechanisms proposed include CYP3A4 inhibition. As concomitant use of valproate and quetiapine is now quite frequent in bipolar disorder, this potential interaction should be closely monitored, especially in the elderly.

Topics: Aged; Antimanic Agents; Bipolar Disorder; Cognition Disorders; Cytochrome P-450 CYP3A; Dibenzothiazepines; Drug Interactions; Drug Monitoring; Drug Therapy, Combination; Female; Humans; Parkinson Disease, Secondary; Quetiapine Fumarate; Treatment Outcome; Valproic Acid

The purpose of this study was to determine preventive and protective effects of chronic orally administration with quetiapine (QUE) against anxiety-like behavior and cognitive impairments in rats exposed to the enhanced single prolonged stress (ESPS), an animal model that is used to study post-traumatic stress disorder (PTSD), and to detect changes in the expression of cortical phosphorylated p44/42 extracellular-regulated protein kinase (pERK1/2). Before or after exposure to ESPS paradigm, consisting of 2-h constraint, 20-min forced swimming, ether-induced loss of consciousness, and an electric foot shock, rats were given orally QUE (10 mg/kg daily) for 14 days. Animals were then tested in the open field (OF), elevated plus-maze (EPM), and Morris water maze (MWM). Brains were removed for immunohistochemical staining of pERK1/2. ESPS exposure resulted in pronounced anxiety-like behavior compared to unexposed animals. ESPS-exposed animals also displayed marked learning and spatial memory impairments. However, QUE treatment (both before and after ESPS exposure) significantly ameliorated anxiety-like behavior, learning and spatial memory impairments. ESPS also markedly reduced the expression of pERK1/2 in the prefrontal cortex, medial amygdala nucleus, and cingulate gyrus. Both before and after ESPS exposure QUE treatments significantly elevated the reduced pERK1/2 expression in the three brain regions. QUE has preventive and protective effects against stress-associated symptoms and the changes in pERK1/2 functions may be associated with the pathophysiology of traumatic stress and the therapeutic efficacy of anti-PTSD therapy.

Topics: Anesthetics, Inhalation; Animals; Antipsychotic Agents; Anxiety Disorders; Cognition Disorders; Dibenzothiazepines; Disease Models, Animal; Electroshock; Ether; Extracellular Signal-Regulated MAP Kinases; Male; MAP Kinase Signaling System; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Neurons; Prefrontal Cortex; Quetiapine Fumarate; Rats; Rats, Sprague-Dawley; Stress Disorders, Post-Traumatic; Swimming; Unconsciousness

Topics: Adult; Antipsychotic Agents; Case-Control Studies; Cognition Disorders; Dibenzothiazepines; Emotions; Facial Expression; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pattern Recognition, Visual; Quetiapine Fumarate; Schizophrenia, Paranoid; Treatment Outcome

Topics: Amisulpride; Antipsychotic Agents; Benzodiazepines; Cognition; Cognition Disorders; Dibenzothiazepines; Drug Administration Schedule; Haloperidol; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Reaction Time; Schizophrenia; Sulpiride; Thiazoles

Topics: Aged; Antipsychotic Agents; Cognition Disorders; Dibenzothiazepines; Dystonia; Female; Humans; Quetiapine Fumarate; Spasm

Accumulating evidence suggests that alpha(1)-adrenoceptors may be involved in the mechanisms of action of some antipsychotic drugs. The present study was undertaken to examine the effects of quetiapine, an atypical antipsychotic drug with alpha(1)-adrenoceptor antagonism, on cognitive deficits in mice after repeated administration of the NMDA receptor antagonist phencyclidine (PCP). Subsequent subchronic (14 days) administration of quetiapine (1.0, 10, or 30 mg/kg, p.o.) attenuated PCP (10 mg/kg/day for 10 days)-induced cognitive deficits in mice, in a dose dependent manner. Furthermore, PCP (10 mg/kg)-induced cognitive deficits were also significantly ameliorated by subsequent subchronic (14 days) administration of the selective alpha(1)-adrenoceptor antagonist prazosin (1.0 mg/kg/day, p.o.). Moreover, Western blot analysis revealed that levels of two subtypes (alpha(1A) and alpha(1B)) of alpha(1)-adrenoceptors were significantly lower in the brains of PCP-treated mice than in those of saline-treated mice. These findings suggest that repeated PCP administration could decrease the density of alpha(1)-adrenoceptors in mouse brain, and that subsequent subchronic administration of quetiapine might ameliorate PCP-induced cognitive deficits via alpha(1)-adrenoceptors. Therefore, it is likely that antagonism at alpha(1)-adrenoceptors is involved in the mechanism underlying quetiapine's psychopharmacological action.

Topics: Adrenergic alpha-Antagonists; Analysis of Variance; Animals; Antipsychotic Agents; Brain; Cognition; Cognition Disorders; Dibenzothiazepines; Disease Models, Animal; Exploratory Behavior; Gene Expression Regulation; Male; Mice; Mice, Inbred ICR; Phencyclidine; Prazosin; Quetiapine Fumarate; Receptors, Adrenergic, alpha-1; Time Factors

We aimed to assess whether executive functioning improved over time in a sample of borderline personality disorder (BPD) subjects that took part in a quetiapine treatment trial.. Performance on the following neurocognitive tasks was assessed at enrolment and at the end of the 12 weeks quetiapine treatment: Trail Making Task, Word Fluency Task and Tower of London Task. Forty-one BPD patients were recruited, of whom 32 completed the trial. An intention-to-treat analysis with a mixed linear model was applied.. The data show that participants significantly improved on most executive functioning measures. Patients' scores decreased significantly (mean [SD] difference; p-value) on the Trail Making Task Part A (11.7 [2.3]; p < 0.0001), Part B (51.8 [9.2]; p < 0.0001) and 'B minus A' (40.1 [8.2]; p < 0.0001), on a Phonological (15.9 [1.6]; p < 0.0001) and Semantic (9.8 [1.1]; p < 0.0001) Verbal Fluency tasks, and on the Tower of London total correct score (2.5 [0.4]; p < 0.0001), total move score (29.5 [4.5]; p < 0.0001) and total time (172.9 [35.8]; p < 0.0001).. In this study we have demonstrated that executive functioning in BPD is improved after treatment with quetiapine. Neurocognitive measures of executive functioning should be considered as valuable outcomes in the study of treatment efficacy in BPD.

Topics: Adolescent; Adult; Antipsychotic Agents; Borderline Personality Disorder; Cognition Disorders; Dibenzothiazepines; Executive Function; Female; Humans; Linear Models; Male; Neuropsychological Tests; Quetiapine Fumarate; Young Adult

This article describes the spectrum of recurrent thoughts and behaviors that can result from frontotemporal dementia (FTD) and its variants. Although repetitive behaviors can result from a range of brain disorders, FTD is the most common neurologic cause of new-onset recurrent thoughts and behaviors in middle or late life. Patients with FTD can manifest typical or bizarre compulsions, hoarding, verbal and motor stereotypies and complex tics; self-injurious acts, perseverations; and fixed, obsessional thoughts. The frequency and variability of these repetitive behaviors suggest a common disturbance of orbitofrontal-basal ganglia circuits involved in response inhibition. The amelioration of these recurrent events with the administration of serotonin selective reuptake inhibitors further suggests a serotonergic deficit.

Topics: Aged; Antipsychotic Agents; Basal Ganglia; Cognition Disorders; Dementia; Dibenzothiazepines; Dopamine Agents; Female; Humans; Magnetic Resonance Imaging; Memantine; Neuropsychological Tests; Quetiapine Fumarate; Recurrence; Sertraline; Stereotypic Movement Disorder; Thinking

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Dibenzothiazepines; Dyskinesia, Drug-Induced; Female; Humans; Olanzapine; Quetiapine Fumarate; Time Factors; Withholding Treatment

Cognitive deficits in schizophrenia are severe and do not respond well to available treatments. The development and validation of animal models of cognitive deficits characterizing schizophrenia are crucial for clarifying the underlying neuropathology and discovery of improved treatments for such deficits.. We investigated whether single and repeated administrations of the psychotomimetic phencyclidine (PCP) disrupt performance in the five-choice serial reaction time task (5-CSRTT), a test of attention and impulsivity. We also examined whether PCP-induced disruptions in this task are attenuated by atypical antipsychotic medications.. A single injection of PCP (1.5-3 mg/kg, s.c., 30-min pre-injection time) had nonspecific response-depressing effects. Repeated PCP administration (2 mg/kg for two consecutive days followed by five consecutive days, s.c., 30-min pre-injection time) resulted in decreased accuracy, increased premature and timeout responding, and increased response latencies. The atypical antipsychotic medications clozapine, risperidone, quetiapine, and olanzapine and the typical antipsychotic medication haloperidol did not disrupt 5-CSRTT performance under baseline conditions except at high doses. The response depression induced by a single PCP administration was exacerbated by acute clozapine or risperidone and was unaffected by chronic clozapine. Importantly, chronic clozapine partially attenuated the performance disruptions induced by repeated PCP administration, significantly reducing both the accuracy impairment and the increase in premature responding.. Disruptions in 5-CSRTT performance induced by repeated PCP administration are prevented by chronic clozapine treatment and may constitute a useful animal model of some cognitive symptoms of schizophrenia.

Topics: Animals; Antipsychotic Agents; Attention; Benzodiazepines; Clozapine; Cognition Disorders; Dibenzothiazepines; Disease Models, Animal; Dose-Response Relationship, Drug; Hallucinogens; Haloperidol; Impulsive Behavior; Male; Olanzapine; Phencyclidine; Quetiapine Fumarate; Rats; Rats, Wistar; Reaction Time; Risperidone; Schizophrenia

Atypical antipsychotics clozapine, olanzapine, and quetiapine have significant affinity for the muscarinic receptors in vitro, while aripiprazole, risperidone, and ziprasidone do not. Dissimilarity in binding profiles may contribute to the reported differences in the anticholinergic effects of these antipsychotics. However, it is difficult with the available data to predict the likelihood of anticholinergic effects occurring with various doses of an atypical antipsychotic.. We developed a model to assess the potential anticholinergic activity (AA) of atypical antipsychotics at therapeutic doses. A radioreceptor assay was used to measure in vitro AA at 6 clinically relevant concentrations of aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone. Using published pharmacokinetic data, in combination with the measured in vitro AA, dose-AA curves were generated.. Clozapine, and to a lesser extent olanzapine and quetiapine showed dose-dependent increases in AA. At therapeutic doses, the AA (in pmol/mL of atropine equivalents) was estimated to range from 27-250, 1-15, and 0-5.4 pmol/mL for clozapine, olanzapine, and quetiapine, respectively. Aripiprazole, risperidone, and ziprasidone did not demonstrate AA at any of the concentrations studied.. Therapeutic doses of clozapine, olanzapine, and, to a lesser extent, quetiapine are associated with clinically relevant AA.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Binding Sites; Clozapine; Cognition Disorders; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Male; Neuropsychological Tests; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Receptors, Cholinergic; Risperidone; Schizophrenia; Thiazoles

Topics: Adult; Cognition Disorders; Dibenzothiazepines; Drug Therapy, Combination; Humans; Male; Pergolide; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

Molecular components of the dopaminergic system may play an important role in the pathophysiology of schizophrenia. In this study, we investigated the relationship of the Ser9Gly (S/G) polymorphism of the dopamine D3 receptor (DRD3) and the variable number of tandem repeats (VNTR) polymorphism of the dopamine transporter (DAT) with therapeutic response to atypical antipsychotics (clozapine, olanzapine, quetiapine, risperidone) and cognitive functions. No associations were found between the DRD3 and DAT polymorphisms and schizophrenia. The S/S genotype and the S allele were more frequent in the non-responder patients (n = 28) than in the group of responders (n = 47) (cut-off: >20-point improvement in Global Assessment of Functioning (GAF) scale). The patients with S/S genotype completed fewer categories and had more perseverative errors in the Wisconsin Card Sorting Test (WCST) compared with the S/G patients. The S/S and S/G patients did not differ in positive and negative symptoms, GAF scores, WCST failure to maintain set, and verbal learning. No differences in symptoms or WCST measures were observed in the patients with different DAT genotypes. These results suggest that the S/S genotype of the DRD3 is associated with worse therapeutic response and more severe executive dysfunctions in patients with schizophrenia.

Topics: Adult; Alleles; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Clozapine; Cognition Disorders; Dibenzothiazepines; Dopamine Plasma Membrane Transport Proteins; Female; Gene Frequency; Genotype; Humans; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Minisatellite Repeats; Nerve Tissue Proteins; Olanzapine; Polymorphism, Genetic; Quetiapine Fumarate; Receptors, Dopamine D2; Receptors, Dopamine D3; Risperidone; Schizophrenia

The Intercontinental Schizophrenia Outpatient Health Outcomes (IC-SOHO) study was designed to provide information regarding use and outcome of antipsychotic treatments in a large, diverse population in real practice settings.. Outpatients with schizophrenia (ICD-10 or DSM-IV) who initiated or changed to a new antipsychotic entered this 3-year, naturalistic, prospective observational study. Four monotherapy treatment groups were defined according to the antipsychotic prescribed at baseline, namely olanzapine, risperidone, quetiapine, and haloperidol. Efficacy was assessed using the Clinical Global Impressions-Severity of Illness rating scale (CGI-S), inclusive of subscales for positive, negative, depressive, and cognitive symptoms. Tolerability was assessed by adverse event questionnaires and weight measurements. Six-month findings are described.. At baseline, 5833 participants were prescribed monotherapy and the mean severity of illness was moderate to marked (CGI-S). At 6 months, olanzapine resulted in significantly greater improvements in overall, positive, negative, depressive, and cognitive symptoms compared with quetiapine, risperidone or haloperidol (p <.001). Improvements in overall, negative, and cognitive symptoms were significantly higher for risperidone compared with haloperidol (p <.001), whereas improvements across all symptoms were comparable for quetiapine and haloperidol. Extra-pyramidal symptoms and tardive dyskinesia decreased compared with baseline in the olanzapine, quetiapine, and risperidone groups but increased in the haloperidol group (p <.001, likelihood of extrapyramidal symptoms with haloperidol compared with olanzapine, quetiapine, or risperidone). Sexual function adverse events were most prominent in the haloperidol and risperidone treatment groups. Weight change was significantly greater for olanzapine compared with the other antipsychotics (p <.001).. Our results support the previously reported positive impact of atypical antipsychotics, particularly olanzapine, in patients with schizophrenia.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Dyskinesia, Drug-Induced; Female; Haloperidol; Humans; Hyperprolactinemia; International Classification of Diseases; Male; Observation; Olanzapine; Prospective Studies; Quetiapine Fumarate; Risperidone; Schizophrenia; Severity of Illness Index; Sexual Dysfunction, Physiological; Surveys and Questionnaires; Weight Gain

Neurosarcoidosis is a rare disorder in which psychosis and dementia may occur. They usually appear subsequently to the diagnosis of pulmonary sarcoidosis. We report on a 39-year-old patient who presented with long-term decline and acute onset of psychosis and delirium, and who was found to have neurosarcoidosis.

Topics: Acute Disease; Adult; Antipsychotic Agents; Brain; Brain Diseases; Cognition Disorders; Diagnosis, Differential; Dibenzothiazepines; Humans; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Psychotic Disorders; Quetiapine Fumarate; Sarcoidosis; Tomography, X-Ray Computed

To identify which improvements in cognitive function are associated with symptom resolution in schizophrenic patients treated with atypical antipsychotics.. a prospective open trial with atypical neuroleptics (risperidone, clozapine, quetiapine).. Inpatient and outpatient units, Institute of Psychiatry.. Thirty-nine patients with schizophrenia according to DSM-IV criteria were included. Clinical and cognitive assessment were done at baseline (T0) and again after six months of treatment (T2). Twenty-five patients completed the trial.. New-generation antipsychotics during six months. Patients were considered as responders if their PANSS score decreased at least 20% (n = 15) and non-responders if it did not (n = 10).. a computerized cognitive assessment comprised tests of short-term-memory (digit span), explicit long-term memory (word pair learning), divided attention, selective attention and verbal fluency (orthographic and semantic). Clinical assessment included PANSS and ESRS.. A discriminant function analysis was performed to determine which changes in cognitive performance predicted symptomatic response status. Semantic fluency and orthographic fluency were significant predictors. Together they correctly predicted responder status in 88% of cases. Memory was not a significant predictor of symptomatic response.. Verbal fluency discriminated the responder from the non-responder group during a pharmacological treatment.

Topics: Adult; Antipsychotic Agents; Attention; Clozapine; Cognition Disorders; Dibenzothiazepines; Female; Humans; Male; Memory, Short-Term; Middle Aged; Neuropsychological Tests; Psychiatric Status Rating Scales; Quetiapine Fumarate; Retention, Psychology; Risperidone; Schizophrenia; Schizophrenic Language; Schizophrenic Psychology; Treatment Outcome; Verbal Behavior