olanzapine and Cognition-Disorders

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Brain; Cognition Disorders; Dementia; Humans; Huntington Disease; Magnetic Resonance Imaging; Male; Memory, Short-Term; Mood Disorders; Olanzapine; Paroxetine

An advance in the treatment of schizophrenia is the development of long-acting intramuscular formulations of antipsychotics, such as olanzapine long-acting injection (LAI). During clinical trials, a post-injection syndrome characterized by signs of delirium and/or excessive sedation was identified in a small percentage of patients following injection with olanzapine LAI.. Safety data from all completed and ongoing trials of olanzapine LAI were reviewed for possible cases of this post-injection syndrome. Descriptive analyses were conducted to characterize incidence, clinical presentation, and outcome. Regression analyses were conducted to assess possible risk factors.. Based on approximately 45,000 olanzapine LAI injections given to 2054 patients in clinical trials through 14 October 2008, post-injection delirium/sedation syndrome occurred in approximately 0.07% of injections or 1.4% of patients (30 cases in 29 patients). Symptomatology was consistent with olanzapine overdose (e.g., sedation, confusion, slurred speech, altered gait, or unconsciousness). However, no clinically significant decreases in vital signs were observed. Symptom onset ranged from immediate to 3 to 5 hours post injection, with a median onset time of 25 minutes post injection. All patients recovered within 1.5 to 72 hours, and the majority continued to receive further olanzapine LAI injections following the event. No clear risk factors were identified.. Post-injection delirium/sedation syndrome can be readily identified based on symptom presentation, progression, and temporal relationship to the injection, and is consistent with olanzapine overdose following probable accidental intravascular injection of a portion of the olanzapine LAI dose. Although there is no specific antidote for olanzapine overdose, patients can be treated symptomatically as needed. Special precautions include use of proper injection technique and a post-injection observation period.. ClinicalTrials.gov ID; URL: http://http//www.clinicaltrials.gov/: NCT00094640, NCT00088478, NCT00088491, NCT00088465, and NCT00320489.

Topics: Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Cognition Disorders; Delayed-Action Preparations; Delirium; Drug Administration Schedule; Drug Overdose; Drug-Related Side Effects and Adverse Reactions; Humans; Incidence; Injections, Intramuscular; Olanzapine; Risk Factors; Schizophrenia; Sleep; Syndrome; Treatment Outcome

This study was conducted to determine the effect of olanzapine treatment on cognition in elderly patients with behavioral and psychiatric symptoms (BPSD) associated with dementia.. This was a post-hoc analysis of three randomized double-blind, clinical trials of olanzapine (n = 682) vs placebo (n = 257) in dementia patients with BPSD in long-term or continuing-care settings. One study was 6 weeks long; the other two were 10 weeks duration, and their data were combined. Patients were subgrouped according to baseline Mini Mental State Examination (MMSE) scores: Group I = 23-26; Group II = 19-22; Group III = 14-18; Group IV = 7-13; Group V = 1-6. BPSD was assessed by the Neuropsychiatric Inventory (NPI).. Within-treatment group cognitive decline in patients was significant in the combined studies, but not in the 6-week study. Between-treatment cognitive changes were non-significant in the 6-week study, but showed a statistical trend in the combined studies (olanzapine, -0.78 +/- 0.19 vs placebo, -0.32 +/- 0.25; p = 0.06). In the subgroup analysis, there was a significant between-treatment difference in cognitive changes in MMSE subgroup IV in the combined studies (olanzapine, -0.63 +/- 0.26 vs placebo, 0.27 +/- 0.41, p = 0.04). Improvement in BPSD was correlated with better cognitive outcome (r = -0.2; p < 0.01).. Although the overall differences in cognitive changes in patients treated with olanzapine vs placebo were small and non-significant, negative effects on cognition in some patients cannot be excluded, especially in patients with more pronounced cognitive decline or whose behavioral and psychiatric symptoms are not responding to treatment.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Dementia; Double-Blind Method; Female; Humans; Male; Neuropsychological Tests; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Randomized Controlled Trials as Topic; Social Behavior Disorders

Topics: Amisulpride; Antipsychotic Agents; Aripiprazole; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Cognition Disorders; Drug Tolerance; Dyskinesia, Drug-Induced; Haloperidol; Humans; Olanzapine; Piperazines; Quinolones; Risperidone; Schizophrenia; Sulpiride; Time Factors

Olanzapine, a thienobenzodiazepine derivative, is a second generation (atypical) antipsychotic agent which has proven efficacy against the positive and negative symptoms of schizophrenia. Compared with conventional antipsychotics, it has greater affinity for serotonin 5-HT2A than for dopamine D2 receptors. In large, well controlled trials in patients with schizophrenia or related psychoses, olanzapine 5 to 20 mg/day was significantly superior to haloperidol 5 to 20 mg/day in overall improvements in psychopathology rating scales and in the treatment of depressive and negative symptoms, and was comparable in effects on positive psychotic symptoms. The 1-year risk of relapse (rehospitalisation) was significantly lower with olanzapine than with haloperidol treatment. In the first double-blind comparative study (28-week) of olanzapine and risperidone, olanzapine 10 to 20 mg/day proved to be significantly more effective than risperidone 4 to 12 mg/day in the treatment of negative and depressive symptoms but not on overall psychopathology symptoms. In contrast, preliminary results from an 8-week controlled study suggested risperidone 2 to 6 mg/day was superior to olanzapine 5 to 20 mg/day against positive and anxiety/depressive symptoms (p < 0.05), although consistent with the first study, both agents demonstrated similar efficacy on measures of overall psychopathology. Improvements in general cognitive function seen with olanzapine treatment in a 1-year controlled study of patients with early-phase schizophrenia, were significantly greater than changes seen with either risperidone or haloperidol. However, preliminary results from an 8-week trial showed comparable cognitive enhancing effects of olanzapine and risperidone treatment in patients with schizophrenia or schizoaffective disorder. Several studies indicate that olanzapine has benefits against symptoms of aggression and agitation, while other studies strongly support the effectiveness of olanzapine in the treatment of depressive symptomatology. Olanzapine is associated with significantly fewer extrapyramidal symptoms than haloperidol and risperidone. In addition, olanzapine is not associated with a risk of agranulocytosis as seen with clozapine or clinically significant hyperprolactinaemia as seen with risperidone or prolongation of the QT interval. The most common adverse effects reported with olanzapine are bodyweight gain, somnolence, dizziness, anticholinergic effects (constipation and dry mouth) and. Olanzapine demonstrated superior antipsychotic efficacy compared with haloperidol in the treatment of acute phase schizophrenia, and in the treatment of some patients with first-episode or treatment-resistant schizophrenia. The reduced risk of adverse events and therapeutic superiority compared with haloperidol and risperidone in the treatment of negative and depressive symptoms support the choice of olanzapine as a first-line option in the management of schizophrenia in the acute phase and for the maintenance of treatment response.

Topics: Adolescent; Aged; Animals; Antipsychotic Agents; Benzodiazepines; Child; Child, Preschool; Cognition Disorders; Cost-Benefit Analysis; Cytochrome P-450 Enzyme System; Depression; Drug Interactions; Haloperidol; Humans; Olanzapine; Pirenzepine; Quality of Life; Randomized Controlled Trials as Topic; Receptors, Serotonin; Risperidone; Schizophrenia

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

Cognitive impairment is a central feature of schizophrenia and has been correlated with negative symptoms and impaired social functioning. There is a growing body of data suggesting that the so-called atypical antipsychotic drugs (e.g. clozapine, risperidone, and olanzapine) are better at enhancing cognitive function than traditional neuroleptics. Preclinical studies of information processing using a pre-pulse inhibition model show that the mechanism of action of both olanzapine and clozapine for cognitive enhancement may involve glutamatergic/N-methyl-D-aspartate (NMDA) antagonism. Using positron emission tomography, we have described the metabolic and neurochemical correlates of cognitive impairment induced by glutamatergic/NMDA antagonism. A better understanding of the underlying causes of cognitive impairment may contribute to elucidating the pathophysiology of schizophrenia and the development of more efficacious treatments for this disorder.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Cognition Disorders; Glutamic Acid; Haloperidol; Humans; N-Methylaspartate; Olanzapine; Pirenzepine; Risperidone; Schizophrenia; Schizophrenic Psychology

Cognitive function is markedly impaired in most patients with schizophrenia. Antecedents of this impairment are evident in childhood. The cognitive disability is nearly fully developed at the first episode of psychosis in most patients. The contribution of cognitive impairment to outcome in schizophrenia, especially work function, has been established. Preliminary results indicate that cognitive function, along with disorganization symptoms, discriminate schizophrenia patients who are able to work full-time from those who are not. Typical neuroleptic drugs lack the ability to improve the various domains of cognitive function impaired in schizophrenia. Atypical antipsychotic drugs pharmacologically related to clozapine-quetiapine, olanzapine, risperidone, sertindole, and ziprasidone--share the ability to produce fewer extrapyramidal symptoms than typical neuroleptic drugs and more potent antagonism of serotonin2a relative to dopamine2 receptors. However, they have a number of different clinical effects. We have identified all the studies of clozapine, olanzapine, and risperidone that provide data on their effects on cognition in schizophrenia. Data for each drug are reviewed separately in order to identify differences among them in their effects on cognition. Twelve studies that report cognitive effects of clozapine are reviewed. These studies provide (1) strong evidence that clozapine improves attention and verbal fluency and (2) moderate evidence that clozapine improves some types of executive function. However, results of the effects of clozapine on working memory and secondary verbal and spatial memory were inconclusive. Risperidone has relatively consistent positive effects on working memory, executive functioning, and attention, whereas improvement in verbal learning and memory was inconsistent. Preliminary evidence presented here suggests that olanzapine improves verbal learning and memory, verbal fluency, and executive function, but not attention, working memory, or visual learning and memory. Thus, atypical antipsychotic drugs as a group appear to be superior to typical neuroleptics with regard to cognitive function. However, available data suggest that these drugs produce significant differences in specific cognitive functions. These differences may be valuable adjunctive guides for their use in clinical practice if cognitive improvements reach clinical significance. The effects of the atypical antipsychotic drugs on cholinergic and 5-HT2a-mediat

Topics: Antipsychotic Agents; Attention; Benzodiazepines; Clinical Trials as Topic; Clozapine; Cognition Disorders; Humans; Mental Recall; Neuropsychological Tests; Olanzapine; Pirenzepine; Risperidone; Verbal Learning

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

Topics: Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Clozapine; Cognition Disorders; Humans; Olanzapine; Pirenzepine; Schizophrenia; Schizophrenic Psychology

Cognitive impairment is a relatively frequent aspect of schizophrenia. Deficits are most prominent in tasks involving attention, memory, and executive function. Although some research suggests that deterioration is progressive, these deficits appear to be relatively stable over time. Imaging and biochemical studies show that schizophrenia is characterized by a number of morphological, hemodynamic, and neurochemical abnormalities within systems integrating the cortex, temporal lobes, and various limbic structures. Neurochemical assays suggest that the neurotransmitters serotonin, dopamine, and glutamate play a significant role in the disease-associated decrement. Cognitive impairment in schizophrenia impedes psychosocial performance and eventual reintegration into society and is therefore an especially relevant target in the development of new therapeutic modalities. Atypical agents, such as clozapine and olanzapine, hold special promise in this area.

Topics: Antipsychotic Agents; Benzodiazepines; Cerebral Cortex; Clozapine; Cognition Disorders; Dopamine; Glutamic Acid; Humans; Limbic System; Olanzapine; Pirenzepine; Schizophrenia; Schizophrenic Psychology; Serotonin

To examine whether cerebrovascular risk, executive function, and processing speed are associated with acute treatment outcome of psychotic depression in older adults.. The authors analyzed data from 142 persons aged 60 years or older with major depression with psychotic features who participated in a 12-week randomized controlled trial (RCT) comparing olanzapine plus sertraline with olanzapine plus placebo. The independent variables were baseline cerebrovascular risk (Framingham Stroke Risk Score), baseline executive function (Stroop interference score and the initiation/perseveration subscale of the Mattis Dementia Rating Scale), and baseline processing speed (color and word reading components of the Stroop). The outcome variable was change in severity of depression, measured by the 17-item Hamilton Depression Rating Scale total score, during the course of the RCT.. Greater baseline cerebrovascular risk was significantly associated with less improvement in depression severity over time, after controlling for pertinent covariates. Neither executive function nor processing speed predicted outcome.. This study suggests an association of cerebrovascular risk, but not executive function or processing speed, with treatment outcome of major depression with psychotic features in older adults.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Cerebrovascular Disorders; Cognition; Cognition Disorders; Depressive Disorder, Major; Double-Blind Method; Executive Function; Humans; Mental Processes; Middle Aged; Neuropsychological Tests; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Reaction Time; Risk; Sertraline; Severity of Illness Index; Stroop Test; Treatment Outcome; Young Adult

Identify moderators of treatment outcome from antipsychotic pharmacotherapy in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) trial. Specifically, we used logistic regression and receiver operating characteristic (ROC) analysis to explore the association between baseline characteristics and treatment outcomes in the CATIE trial.. This is a secondary analysis of the CATIE trial in which 1,460 adults with a DSM-IV diagnosis of schizophrenia were randomly assigned to olanzapine, perphenazine, quetiapine, risperidone, or ziprasidone treatment for up to 18 months or until discontinuation between January 2001 and December 2004. Logistic regression was used to examine baseline characteristics associated with remission, response, and treatment continuation at 3 and 6 months of treatment. ROC analyses identified subgroups associated with similar likelihood of treatment outcome. Remission was defined by scores of selected items on psychoticism, disorganization, and negative symptoms. Response was defined as a 50% or greater improvement on the Positive and Negative Syndrome Scale.. The most consistent predictors of poor outcome on all variables were low scores on neurocognitive tests (in particular verbal memory) (OR = 1.13-1.49, P< .05); previous reported side effects (OR = 0.49-0.69, P < .05); negative attitude to medication (OR = 1.03-1.10, P < .05); comorbid depression (OR = 0.47-0.51, P < .05); psychosocial factors such as unemployment (OR = 0.74-0.75, P <.05), homelessness (OR = 0.54, P <.05), and living alone (OR = 1.58-1.94, P < .01); and random assignment to a medication other than olanzapine (OR = 1.54-2.04, P < .01). ROC analysis demonstrated prognostic subgroups with large differences in response likelihood.. Baseline characteristics in schizophrenia are informative regarding clinically important treatment outcomes with respect to antipsychotic pharmacotherapy. Further research should examine whether interventions that target improvement of patients' deficits in neuropsychological function and attitude toward medication as well as decreasing patients' social isolation can improve treatment outcomes with antipsychotic treatment in schizophrenia.. ClinicalTrials.gov identifier: NCT00014001.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Female; Follow-Up Studies; Humans; Male; Medication Adherence; Middle Aged; Olanzapine; Outcome Assessment, Health Care; Remission Induction; Schizophrenia; Socioeconomic Factors; Young Adult

Impact of dose reduction of atypical antipsychotics on cognitive function has not been investigated in stable patients with schizophrenia. In this open-label, 28-week, randomized controlled trial, stable patients with schizophrenia treated with risperidone or olanzapine were randomly assigned to the reduction group (dose reduced by 50% in 4 weeks and then maintained) or maintenance group (dose kept constant). Assessments at baseline and week 28 included the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Positive and Negative Syndrome Scale (PANSS), and Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). Sixty-one patients were enrolled; 2 of 31 (6.5%) and 5 of 30 (16.7%) patients prematurely withdrew from the study in the reduction and maintenance groups, respectively. While no significant differences in change in the PANSS total score were observed between the 2 groups, the reduction group showed significantly greater improvements in the RBANS and DIEPSS total scores compared with the maintenance group (mean ± SD, +7.0±7.1 vs -0.1±8.0, P < .001; -0.9±1.7 vs +0.1±1.2, P = .010, respectively). This 6-month pilot study suggests that risperidone or olanzapine dose reduction of 50% can improve cognitive function for stable patients with schizophrenia. Due to the open-label design, small sample size, and short study duration, however, there is a need to confirm the finding through double-blind, larger scale trials with longer follow-up periods. Moreover, potential risks of relapse following antipsychotic dose reduction should be thoroughly investigated in longer term studies.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Drug Administration Schedule; Female; Humans; Maintenance Chemotherapy; Male; Middle Aged; Neuropsychological Tests; Olanzapine; Pilot Projects; Psychiatric Status Rating Scales; Risperidone; Schizophrenia; Treatment Outcome

Serotonin (5-hydroxytryptamine) receptor 2a (5-HT2AR) signaling is important for modulation of corticostriatal pathways and prefrontal activity during cognition. Furthermore, newer antipsychotic drugs target 5-HT2AR. A single-nucleotide polymorphism in the 5-HT2AR gene (HTR2A rs6314, C>T; OMIM 182135) has been weakly associated with differential 5-HT2AR signaling and with physiologic as well as behavioral effects.. To use a hierarchical approach to determine the functional effects of this single-nucleotide polymorphism on 5-HT2AR messenger RNA and protein expression, on prefrontal phenotypes linked with genetic risk for schizophrenia, and on treatment with olanzapine.. In silico predictions, in vitro, and case-control investigations.. Academic and clinical facilities.. The postmortem study included 112 brains from healthy individuals; the in vivo investigation included a total sample of 371 healthy individuals and patients with schizophrenia. EXPOSURES Patients received olanzapine monotherapy for 8 weeks.. In silico predictions, messenger RNA, and protein expression in postmortem human prefrontal cortex and HeLa cells, functional magnetic resonance imaging prefrontal activity and behavior during working memory and attention in healthy individuals, and response to an 8-week trial of olanzapine treatment in patients with schizophrenia.. Bioinformatic analysis predicted that rs6314 alters patterns of splicing, with possible effects on HTR2A expression. Moreover, the T allele was associated with reduced prefrontal messenger RNA expression in postmortem prefrontal cortex, with reduced protein expression in vitro, inefficient prefrontal blood oxygen level-dependent functional magnetic resonance imaging response during working memory and attentional control processing, and impaired working memory and attention behavior, as well as with attenuated improvement in negative symptoms after olanzapine treatment.. Our results suggest that HTR2A rs6314 affects 5-HT2AR expression and functionally contributes to genetic modulation of known endophenotypes of schizophrenia-like higher-level cognitive behaviors and related prefrontal activity, as well as response to treatment with olanzapine.

Topics: Adult; Alleles; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Endophenotypes; Female; Genetic Variation; HeLa Cells; Humans; Magnetic Resonance Imaging; Male; Olanzapine; Prefrontal Cortex; Receptor, Serotonin, 5-HT2A; Schizophrenia; Selective Serotonin Reuptake Inhibitors; Young Adult

Antipsychotic drugs exert antipsychotic effects by blocking dopamine D2 receptors in the treatment of schizophrenia. However, effects of D2 receptor blockade on neurocognitive function still remain to be elucidated. The objective of this analysis was to evaluate impacts of estimated dopamine D2 receptor occupancy with antipsychotic drugs on several domains of neurocognitive function in patients with schizophrenia in the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) trial.. The dataset from the CATIE trial was used in the present analysis. Data were extracted from 410 subjects who were treated with risperidone, olanzapine, or ziprasidone, received assessments for neurocognitive functions (verbal memory, vigilance, processing speed, reasoning, and working memory) and psychopathology, and provided plasma samples for the measurement of plasma antipsychotic concentrations. D2 receptor occupancy levels on the day of neurocognitive assessment were estimated from plasma antipsychotic concentrations, using population pharmacokinetic analysis and our recently developed model. A multivariate general linear model was used to examine effects of clinical and demographic characteristics, including estimated D2 occupancy levels, on neurocognitive functions.. D2 occupancy levels showed significant associations with the vigilance and the summary scores. Neurocognitive functions, including vigilance, were especially impaired in subjects who showed D2 receptor occupancy level of >77%.. These findings suggest a nonlinear relationship between prescribed antipsychotic doses and overall neurocognitive function and vigilance. This study shows that D2 occupancy above approximately 80% not only increases the risk for extrapyramidal side effects as consistently reported in the literature but also increases the risk for cognitive impairment.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Dopamine D2 Receptor Antagonists; Female; Humans; Linear Models; Male; Middle Aged; Olanzapine; Piperazines; Receptors, Dopamine D2; Risperidone; Schizophrenia; Schizophrenic Psychology; Thiazoles; 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

The objective of this paper was to investigate the prognostic and predictive value of a small panel of independent and clinically important factors based on symptom improvement, baseline cognitive impairment, and weight change during the early treatment phase.. The study sample was based on a double-blind, 6-month continuation study of ziprasidone and olanzapine (N=94). We developed a parsimonious 6-month GAF prediction function using a logistic regression model, and evaluated its predictive accuracy and performance using bootstrap estimates of c-statistics and error in predicted probability.. At up to 6 months of follow-up, 52 (55%) of all subjects treated with ziprasidone or olanzapine met the responder criterion of ≥50% improvement in GAF. At Week 2 (acute phase), the majority of ziprasidone (75%) and olanzapine (70%) patients showed greater than 25% improvement in the BPRS psychotic symptom subscale score. These early psychotic symptom responders (Week 2) showed significantly greater improvement in global functioning than early non-responders at all time points (Week 6 and Month 6) (all p's<0.05), confirming early response as an indicator of continued responsiveness to treatment over at least 6 months. A multivariate prediction function based on baseline neurocognitive scores and GAF, early reduction of psychotic symptoms at 2 weeks, and percentage of weight change observed at 6 weeks (All p's <0.05), showed statistically acceptable predictive performance (boostrap c-statistics=0.8598).. Our findings suggest that a parsimonious model incorporating a psychotic symptom assessment score, baseline neurocognitive performance, and risk of weight gain can be developed for predicting patients' likelihood of achieving favorable, long-term treatment outcomes.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cognition; Cognition Disorders; Double-Blind Method; Drug Monitoring; Drug Resistance; Female; Follow-Up Studies; Humans; Male; Middle Aged; Models, Biological; Olanzapine; Patient Dropouts; Piperazines; Prognosis; Psychiatric Status Rating Scales; Schizophrenia; Thiazoles; Weight Gain

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

Second-generation antipsychotics yield only a modest improvement in cognitive benefit compared to first-generation antipsychotics. Aripiprazole, which is a partial dopamine D2 receptor agonist, may have an impact on cognitive dysfunction in patients with schizophrenia. This study administered aripiprazole or placebo to 36 outpatients with schizophrenia also receiving risperidone or olanzapine for 12 weeks in a double-blind, randomized, placebo-controlled study. Cognitive function was evaluated using the Brief Assessment of Cognition in Schizophrenia (BACS) just prior to drug administration as well as 12 weeks after. The PANSS and UKU side effect rating scales were used to evaluate the clinical response to additional treatment with aripiprazole. In a primary analyses, ANCOVA showed that there was an interaction between the treatment group and time for verbal fluency (p < 0.05), but not for any domain in BACS, PANSS or UKU side effect rating scales. Upon secondary analysis, however, the ameliorative change in motor speed as assessed by the BACS (p < 0.05) for those receiving aripiprazole was greater than that for the placebo group, whereas deterioration in verbal fluency (p < 0.01) and executive function (p < 0.01) in those receiving aripiprazole was significantly greater than in the placebo group. These results suggest that adjunctive treatment with aripiprazole improves motor speed but worsens some cognitive functions. It is likely that these effects are due to the dopamine D2 antagonistic effect of aripiprazole.

Topics: Adult; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Chemotherapy, Adjuvant; Cognition; Cognition Disorders; Double-Blind Method; Female; Humans; Male; Olanzapine; Piperazines; Quinolones; Receptors, Dopamine D2; Risperidone; Schizophrenia

Weight gain is commonly observed with olanzapine treatment. Zonisamide is an antiepileptic drug associated with weight loss. This study examined the effectiveness of zonisamide in preventing weight gain in 42 patients beginning olanzapine for bipolar disorder or schizophrenia. Each patient had a body mass index of 22 mg/kg or greater and was randomized to taking olanzapine with either zonisamide (n = 20) or placebo (n = 22) for 16 weeks. The primary outcome measure was change in body weight in kilograms from baseline. In the primary analysis using longitudinal regression, patients who received zonisamide had a significantly slower rate of weight gain and increase in body mass index than those who received placebo. The patients treated with zonisamide gained a mean (SD) of 0.9 (3.3) kg, whereas those treated with placebo gained a mean (SD) of 5.0 (5.5) kg; P = 0.01. None of the patients in the zonisamide group, compared with 7 patients (33%) in the placebo group, gained 7% of body weight or greater from baseline (Fisher exact test, P = 0.009). The zonisamide group, however, reported significantly more cognitive impairment as an adverse event than the placebo group (25% vs 0, respectively; P = 0.02). Zonisamide was effective for mitigating weight gain in patients with bipolar disorder or schizophrenia initiating treatment with olanzapine but was associated with cognitive impairment as an adverse event.

Topics: Adult; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cognition Disorders; Double-Blind Method; Female; Follow-Up Studies; Humans; Isoxazoles; Male; Middle Aged; Olanzapine; Regression Analysis; Schizophrenia; Treatment Outcome; Weight Gain; Young Adult; Zonisamide

To assess neurocognitive outcomes following antipsychotic intervention in youth enrolled in the National Institute of Mental Health (NIMH)-funded Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS).. Neurocognitive functioning of youth (ages 8 to 19 years) with schizophrenia or schizoaffective disorder was evaluated in a four-site, randomized, double-blind clinical trial comparing molindone, olanzapine, and risperidone. The primary outcomes were overall group change from baseline in neurocognitive composite and six domain scores after 8 weeks and continued treatment up to 52 weeks. Age and sex were included as covariates in all analyses.. Of 116 TEOSS participants, 77 (66%) had post-baseline neurocognitive data. No significant differences emerged in the neurocognitive outcomes of the three medication groups. Therefore, the three treatment groups were combined into one group to assess overall neurocognitive outcomes. Significant modest improvements were observed in the composite score and in three of six domain scores in the acute phase, and in four of six domain scores in the combined acute and maintenance phases. Partial correlation analyses revealed very few relationships among Positive and Negative Syndrome Scale (PANSS) baseline or change scores and neurocognition change scores.. Antipsychotic intervention in youth with early-onset schizophrenia spectrum disorders (EOSS) led to modest improvement in measures of neurocognitive function. The changes in cognition were largely unrelated to baseline symptoms or symptom change. Small treatment effect sizes, easily accounted for by practice effects, highlight the critical need for the development of more efficacious interventions for the enduring neurocognitive deficits seen in EOSS. Clinical trial registry information-Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS); http://www.clinicaltrials.gov; NCT00053703.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Child; Cognition Disorders; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Molindone; Neuropsychological Tests; Olanzapine; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology

Imaging evidence indicates that brain alterations are primary to the full-blown onset of schizophrenia and seem to progress across time. The potential effects of antipsychotic medication on brain structure represent a key factor in understanding brain changes in psychosis. We aimed to investigate the effects of low doses of haloperidol, risperidone and olanzapine on cortical thickness.. We investigated the effects of risperidone (N=16), olanzapine (N=18) and low doses of haloperidol (N=18) in cortical thickness changes during 1-year follow-up period in a large and heterogeneous sample of schizophrenia spectrum patients. The relationship between cortical thickness changes and clinical and cognitive outcome was also assessed. A group of 45 healthy volunteers was also longitudinally evaluated. Magnetic resonance imaging brain scans (1.5T) were obtained and images were analyzed by using BRAINS2.. There were no significant effects of time (F(1,47)<1.66; P>0.204), treatment group (F(2,47)<1.47; P>0.242) or group-by-time interaction (F(2,47)<1.82; P>0.174) for any of the cortical thickness variables. When the group of healthy controls was included in the analyses, it is of note that group-by-time interaction showed a significant result for the frontal lobe at trend level (F(3,81)=2.686; P=0.052). After the Bonferroni adjustment for multiple comparisons, there were no significant associations between changes in cortical thickness and clinical and cognitive outcome.. Low doses of haloperidol, risperidone, and olanzapine seem to equally affect gray matter cortical thickness, overall and lobes, at the medium-term (1 year). The clinical effectiveness of treatments was not significantly related to changes in cortical thickness.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Cerebral Cortex; Cognition Disorders; Double-Blind Method; Female; Follow-Up Studies; Haloperidol; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Neuropsychological Tests; Olanzapine; Psychiatric Status Rating Scales; Retrospective Studies; Risperidone; Schizophrenia; Young Adult

Duration of untreated psychosis (DUP) has been significantly associated with poor clinical and social outcomes in First Episode Psychosis (FEP) patients, but an association with cognitive outcomes has not been clearly established.. Seventy-seven consecutively admitted, drug-naïve patients with FEP were assessed at baseline and at 1month and 6months. Underlying dimensions of DUP (general prodrome and positive, negative and disorganisation symptoms) were assessed using the Symptom Onset in Schizophrenia (SOS) inventory (Perkins et al., 2000). To assess the effect of DUP on the neuropsychological status of the patients, a linear mixed-effect model was fitted to each neuropsychological dimension. These models included a dichotomised version of DUP (short versus long duration) as a fixed effect, several adjusting variables to account for patient differences, and a random effect to incorporate the longitudinal structure of the data.. Patients with a short duration of untreated negative symptoms (DUNS) or a short duration of untreated positive symptoms (DUPS) outperformed patients with a long duration of untreated symptoms on memory tasks and a pre-attentional visual task but not on measures of verbal fluency, attention, reaction time, visual processing and executive functions.. This study provides additional support for an early intervention to shorten DUP to facilitate a better outcome in memory and attentional domains of FEP patients.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Female; Humans; Longitudinal Studies; Male; Middle Aged; Neuropsychological Tests; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Retrospective Studies; Risperidone; Statistics, Nonparametric; Young Adult

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

The objective of this study, the effect of aripiprazole on clinical symptoms and cognitive function in patients with chronic schizophrenia was compared to that of perospirone and olanzapine. The subjects were 31 patients, they were diagnosed with schizophrenia on the basis of the criteria of the DSM-IV. Clinical symptoms were assessed using Brief Psychiatric Rating Scale (BPRS), and cognitive function was assessed using the Wisconsin Card Sorting Test (Keio Version: KWCST) and the St. Marianna University School of Medicine's Computerized Memory Test (STM-COMET) as executive function and memory/attention function tests at baseline and 8 weeks after switching. As a result, comparison of the BPRS mean total score revealed no significant difference between aripiprazole and the other medications. Aripiprazole resulted in significant changes in the number of categories achieved (CA) and difficulty maintaining set (DMS) compared to olanzapine at the second level of the KWCST. Comparison thus revealed no difference in clinical effect between aripiprazole and the other medications, but might suggest possible differences between aripiprazole and olanzapine in the profiles of the improvement effects on executive function, memory, and attention function.

Topics: Adult; Aged; Antipsychotic Agents; Aripiprazole; Attention; Benzodiazepines; Chronic Disease; Cognition Disorders; Dose-Response Relationship, Drug; Drug Substitution; Executive Function; Female; Humans; Isoindoles; Longitudinal Studies; Male; Memory; Middle Aged; Neuropsychological Tests; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Quinolones; Schizophrenia; Single-Blind Method; Thiazoles; Time Factors; Verbal Learning

A positive relationship between cholesterol levels and cognition has been reported in various human and animal studies, but has never been investigated in schizophrenia. The goal of this study was to examine this relationship in schizophrenic patients randomized to clozapine, olanzapine or haloperidol.. This was a double-blind randomized prospective 12-week study. Participants received a baseline evaluation including a cognitive battery consisting of an evaluation of psychomotor function, general executive function, visual and verbal memory, and visuospatial ability. Their fasting serum cholesterol level was also assessed. The participants were then randomized to clozapine, olanzapine, or haloperidol. They were evaluated at the end of 12 weeks. A general cognitive index (GCI) derived from the cognitive battery was the primary variable.. 82 patients had both baseline and endpoint neurocognitive assessments and cholesterol levels. There was a statistically and clinically significant positive association between change in cholesterol levels and change in GCI. This association was especially pronounced for verbal memory. There was no interaction between medication grouping and cholesterol level; the positive association was observable separately in each medication group. It was very robust and remained significant after we controlled for glucose and triglyceride levels, anticholinergic side effects, medication serum levels, cholesterol lowering medications, and pre-study antipsychotic medications.. Cholesterol levels show a strong association with cognition in schizophrenia in all medication groups. Further research on the role of lipid metabolism in cognition may suggest new treatments for this core deficit of schizophrenia.

Topics: Adolescent; Adult; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Weight; Cholesterol; Clozapine; Cognition Disorders; Double-Blind Method; Female; Follow-Up Studies; Haloperidol; Humans; Male; Middle Aged; Neuropsychological Tests; Olanzapine; Prospective Studies; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Triglycerides; Young Adult

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

Cognitive deficits are a core feature in schizophrenia. Cognitive deficits appear to be present at the onset of schizophrenia and persist after remission of psychotic symptoms. As cognitive deficits are associated with poor functional outcome, they form an important focus of treatment. There are relatively few head-to-head comparisons of the effects of second generation antipsychotics on cognition in recent onset schizophrenia. This is the first study to compare the effects of a short term treatment of olanzapine versus ziprasidone on cognitive functioning in recent onset schizophrenia. An earlier study conducted in chronic patients revealed an enhancement of cognition after treatment for both agents, but the extent of improvement was not significantly different between ziprasidone and olanzapine.. Patients with recent onset schizophrenia with limited previous exposure to medical treatment underwent a double blind randomized controlled treatment trial. Fifty-six patients completed the neuropsychological testing procedure prior to randomization and after eight weeks of treatment and were included in the analysis. We tested cognitive functioning in general and verbal memory in particular. We calculated a single unweighted composite score based on nine cognitive tests to determine general cognitive functioning.. Cognition appeared enhanced after treatment, but was not significantly different between treatment groups, neither for the verbal memory measures, nor for the neurocognitive composite score. Furthermore, cognitive enhancement did not correlate to clinical improvement.. Cognitive deficits are not a reason for preferentially prescribing one of the two second generation antipsychotics tested over the other.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Neuropsychological Tests; Olanzapine; Piperazines; Quality of Life; Schizophrenia; Statistics as Topic; Thiazoles; Verbal Learning; Young Adult

To evaluate the efficacy and tolerability of armodafinil, the longer-lasting isomer of modafinil, as adjunctive therapy in patients with schizophrenia.. This 4-week, randomized, double-blind, placebo-controlled, proof-of-concept study was conducted between July and December 2007. Patients had a history of stable schizophrenia (DSM-IV-TR criteria) for ≥ 8 weeks and were treated with oral risperidone, olanzapine, or paliperidone for ≥ 6 weeks at stable doses for ≥ 4 weeks. Patients were randomly assigned to once-daily placebo or armodafinil 50, 100, or 200 mg. The primary efficacy measure was the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery. Secondary outcome measures included the Positive and Negative Syndrome Scale (PANSS) and the Scale for Assessment of Negative Symptoms (SANS).. Sixty patients were randomly assigned (15 in each group). No apparent differences between groups in the MATRICS composite score were observed (mean ± SD change from baseline to final visit: armodafinil 50 mg, 1.9 ± 6.22; 100 mg, 2.8 ± 7.98; 200 mg, 2.9 ± 4.72; placebo, 2.2 ± 5.06). The mean ± SD changes in PANSS total scores were -6.3 ± 7.25 for armodafinil 200 mg and -1.7 ± 4.89 for placebo at final visit (effect size=0.73; 95% CI, -0.08 to 1.54) and PANSS negative symptoms scores were -3.4 ± 2.07 and 0.1 ± 1.93 (effect size=1.69; 95% CI, 0.78 to 2.60), respectively. Although reductions in SANS total score were observed with both armodafinil and placebo at final visit, no between-group difference was shown. Armodafinil was generally well tolerated, with diarrhea and headache the most commonly reported adverse events. There was no evidence of worsening of psychosis with adjunctive armodafinil.. In this 4-week study, adjunctive armodafinil was not associated with an improvement in cognitive measures, but armodafinil 200 mg/d appeared to mitigate the negative symptoms of schizophrenia. Treatment was generally well tolerated.. clinicaltrials.gov Identifier: NCT00487942.

Topics: Adult; Antipsychotic Agents; Benzhydryl Compounds; Benzodiazepines; Central Nervous System Stimulants; Cognition Disorders; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Isoxazoles; Male; Middle Aged; Modafinil; Olanzapine; Paliperidone Palmitate; Psychiatric Status Rating Scales; Pyrimidines; Risperidone; Schizophrenia; Treatment Outcome

This study assessed the relationship between duration of untreated psychosis (DUP) and cognitive measures in order to assess if longer DUP was associated with worse performance. One hundred two patients with first episode schizophrenia or schizoaffective disorder were assessed on cognitive measures of speed of processing, episodic memory, executive function, and visual spatial processing at baseline (when patients were drug naive and after 16 weeks of olanzapine or risperidone treatment), so that a change score could be derived. DUP was defined by the emergence of psychiatric symptoms and the emergence of psychotic symptoms. Data were analyzed correlationally, parametrically (after the group was divided into long and short DUP by median split), and by regression. We found that DUP for psychotic symptoms in this group of patients was long, with a median of 46 weeks. Neither correlational, parametric analyses in which DUP served as a class variable, nor multiple regression indicated that longer DUP was associated with worse cognition at baseline or smaller magnitude of improvement in cognition. Our results suggest that while early intervention may be critical for symptom amelioration by shortening DUP, early intervention for treatment of psychiatric symptoms may have little or no impact on cognitive function. Furthermore, assuming that cognition is a core symptom of schizophrenia, the notion that ongoing psychosis is somehow toxic for a variety of information processing domains appears questionable.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Double-Blind Method; Early Diagnosis; Female; Humans; Male; Neuropsychological Tests; Olanzapine; Prognosis; Psychiatric Status Rating Scales; Psychometrics; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology; Young Adult

To investigate the neurocognitive effectiveness of haloperidol, risperidone, and olanzapine in first-episode schizophrenia-spectrum disorders.. This prospective, randomized, open-label study was conducted from February 2001 to February 2005. Data for the present investigation were obtained from a large epidemiologic and 3-year longitudinal intervention program of first-episode psychosis (DSM-IV criteria) conducted at the outpatient clinic and the inpatient unit at the University Hospital Marques de Valdecilla, Santander, Spain. One hundred four patients randomly assigned to haloperidol (N = 35), olanzapine (N = 30), or risperidone (N = 39) who completed clinical and cognitive evaluations at baseline, 6 months, and 1 year were included in the final analysis. Thirty-seven healthy individuals were also longitudinally assessed. A neuropsychological battery that comprised 9 cognitive domains was used. The contribution of clinical changes, concomitant medications, and the severity of motor side effects to cognitive changes was controlled. The main outcome measure was cognitive changes at 1-year follow-up.. The 3 treatment groups showed a significant improvement in cognitive scores after 1 year. The differential cognitive effectiveness between antipsychotics was insignificant. The magnitude of cognitive changes was similar in the 3 treatment groups and controls, although a greater improvement on the Finger Tapping Test, Trail Making Test B, and Rey Complex Figure Test was found in the treatment groups. Clinical changes, use of concomitant medications, and the emergence of motor side effects did not significantly account for cognitive changes over time.. Haloperidol, olanzapine, and risperidone were equally effective in treating cognitive deficits of psychosis. The effect of practice clearly contributes to cognitive score improvements after treatment with antipsychotics. Our results provide important information regarding the practical utility of antipsychotic treatments to improve cognition and could have implications for developing novel approaches for cognitive pharmacotherapy in schizophrenia.

Topics: Adult; Amisulpride; Antipsychotic Agents; Benzodiazepines; Brain; Clozapine; Cognition Disorders; Female; Follow-Up Studies; Haloperidol; Humans; Male; Neuropsychological Tests; Olanzapine; Perphenazine; Piperazines; Prospective Studies; Psychotic Disorders; Risperidone; Severity of Illness Index; Sulpiride; Thiazoles

Neurocognitive impairment and psychiatric symptoms have been associated with deficits in psychosocial and occupational functioning in patients with schizophrenia. This post-hoc analysis evaluates the relationships among cognition, psychopathology, and psychosocial functioning in patients with schizophrenia at baseline and following sustained treatment with antipsychotic drugs.. Data were obtained from a clinical trial assessing the cognitive effects of selected antipsychotic drugs in patients with schizophrenia. Patients were randomly assigned to 24 weeks of treatment with olanzapine (n = 159), risperidone (n = 158), or haloperidol (n = 97). Psychosocial functioning was assessed with the Heinrichs-Carpenter Quality of Life Scale [QLS], cognition with a standard battery of neurocognitive tests; and psychiatric symptoms with the Positive and Negative Syndrome Scale [PANSS]. A path-analytic approach was used to evaluate the effects of changes in cognitive functioning on subdomains of quality of life, and to determine whether such effects were direct or mediated via changes in psychiatric symptoms.. At baseline, processing speed affected functioning mainly indirectly via negative symptoms. Positive symptoms also affected functioning at baseline although independent of cognition. At 24 weeks, changes in processing speed affected changes in functioning both directly and indirectly via PANSS negative subscale scores. Positive symptoms no longer contributed to the path-analytic models. Although a consistent relationship was observed between processing speed and the 3 functional domains, variation existed as to whether the paths were direct and/or indirect. Working memory and verbal memory did not significantly contribute to any of the path-analytic models studied.. Processing speed demonstrated direct and indirect effects via negative symptoms on three domains of functioning as measured by the QLS at baseline and following 24 weeks of antipsychotic treatment.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Female; Follow-Up Studies; Haloperidol; Humans; Male; Neuropsychological Tests; Olanzapine; Psychiatric Status Rating Scales; Psychometrics; Quality of Life; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

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

There is uncertainty regarding the onset timing of the cognitive deficiencies of schizophrenia. We investigated whether conversion to psychosis and/or olanzapine altered the neuropsychological course of subjects within the first-ever double blind medication study of the putative schizophrenia first episode prodrome.. Sixty participants in a double blind trial of olanzapine as a treatment for putative prodromal states were assessed at entry (pre-randomization), and again at 6 and 12 months (if they remained non-psychotic), or at any of these points prior to psychosis followed by post-psychosis and 6 months post-psychosis assessments.. Participants who converted to psychosis did not differ from placebo non-converters in pre-randomization global neuropsychological status. Early converters did not differ from later converters in entry neuropsychological status. Subjects who converted after 6 months did not show neuropsychological declines during the initial, pre-psychosis, 6 months. Neuropsychological course did not differ between converters to psychosis and non-converters, or between olanzapine and placebo-assigned subjects.. Neither the onset of frank psychosis nor olanzapine treatment of the prodrome significantly alters neuropsychological course in persons considered to be at high risk at their initial (pre-psychosis) assessment. These findings suggest that the neuropsychological deficiencies associated with psychotic conditions largely pre-exist the first frank psychotic episode.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Cognition; Cognition Disorders; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Neuropsychological Tests; North America; Olanzapine; Placebos; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

The purpose of this study was to compare the effects of olanzapine, clozapine, and haloperidol on neurocognitive function in schizophrenic patients who present with documented episodes of physical aggression and to determine whether change in cognitive function is related to aggression. One hundred physically aggressive schizophrenic inpatients were assigned to a randomized, double-blind, parallel-group, 12-week treatment, and received cognitive evaluations at baseline. There were 33, 34, and 33 subjects in the clozapine, olanzapine, and haloperidol groups, respectively. They were administered a battery of tests assessing psychomotor function, general executive function, visual and verbal memory, and visuospatial ability. A general cognitive index was derived from the above battery. The overall score on the Modified Overt Aggression Scale was used to measure the number and severity of the aggressive events. Psychiatric symptoms and side effects were also assessed. The improvement in the general cognitive index differed significantly among the 3 treatment groups, with olanzapine being superior to both haloperidol and clozapine. Further analyses revealed significantly greater improvement with olanzapine in several cognitive domains. Furthermore, improvement in the general cognitive index was significantly associated with a decrease in aggression in the olanzapine group but not in the other 2 medication groups. In violent schizophrenic patients, olanzapine treatment is associated with better cognitive functioning relative to haloperidol and clozapine. This improvement in neurocognitive function is associated with a decrease in aggressive behavior. As clozapine markedly reduced aggression, there may be different pathways for the antiaggressive effect of olanzapine and that of clozapine.

Topics: Adult; Aggression; Antipsychotic Agents; Benzodiazepines; Clozapine; Cognition Disorders; Double-Blind Method; Female; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Violence

To investigate potential changes and associations in clinical dimensions and cognitive functioning after the first 6 weeks of pharmacological treatment as the relation between cognitive and clinical change may have an impact in determining the importance of cognition as a treatment target.. Patients (n = 42) completed a brief battery of 5 neurocognitive tests within 72 hours of commencing, and 6 weeks after, standard pharmacological treatment. The cognitive testing comprised 5 domains: attention, visuomotor speed, declarative memory, working memory, and executive function. Volunteers (n = 43) were recruited to control for practice effects.. Patients and control subjects improved over time in the raw scores in cognitive tests. Patients' performance, at baseline and end point assessments, was below that of the control subjects in all cognitive variables, except the Stroop interference score. No interaction effect between time and group was found. Further, after controlling for practice effects and adjusting for multiple comparisons, patients' cognitive performance showed no significant improvement. Accordingly, there was no association between clinical improvement and cognitive change. This lack of association was also observed in the subgroup of people who showed decreased scores in negative symptoms.. Cognitive response is not clearly enhanced by antipsychotic drugs and it is not a by-product of clinical recovery during the acute phase (first 6 weeks) of a first-episode nonaffective psychosis.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Female; Haloperidol; Humans; Male; Middle Aged; Neuropsychological Tests; Olanzapine; Psychiatric Status Rating Scales; Psychometrics; Psychotic Disorders; Risperidone; Schizophrenia; Statistics as Topic; Young Adult

AMPA-receptor-positive modulators (Ampakines) facilitate learning and memory in animal models and in preliminary trials in human subjects. CX516 is the first Ampakine to be studied for cognitive enhancement in schizophrenia. Stable schizophrenia patients treated with clozapine (n=52), olanzapine (n=40), or risperidone (n=13) were randomly assigned to add-on treatment with CX516 900 mg three times daily or placebo for 4 weeks. Subjects were assessed with a cognitive battery at baseline, week 4, and at 4-week follow-up. Clinical scales and safety monitoring were also performed. The primary endpoint was the change from baseline in a composite cognitive score at week 4 for the intent-to-treat sample. Additional analyses examined change in symptom rating scores and examined drug effects on patients treated with clozapine separately from patients treated with either olanzapine or risperidone. A total of 105 patients were randomized and 95 (90%) completed the 4-week trial. Patients treated with CX516 did not differ from placebo in change from baseline on the composite cognitive score, or on any cognitive test at weeks 4 or 8. The between groups effect size at week 4 for the cognitive composite score was -0.19 for clozapine-treated patients and 0.24 for patients treated with olanzapine or risperidone. The placebo group improved more on the PANSS total score than the CX516 group; no other clinical rating differed between treatment groups. CX516 was associated with fatigue, insomnia and epigastric discomfort compared to placebo, but was generally well tolerated. CX516 was not effective for cognition or for symptoms of schizophrenia when added to clozapine, olanzapine, or risperidone.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Cognition Disorders; Dioxoles; Double-Blind Method; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Olanzapine; Pilot Projects; Piperidines; Psychiatric Status Rating Scales; Psychomotor Performance; Risperidone; Sample Size; Schizophrenia; Schizophrenic Psychology

This study aimed to evaluate the association of positive and negative symptoms, as well as of neurocognition to functional status in patients with schizophrenia. Participants were 309 veterans with DSM-IV-diagnosed schizophrenia or schizoaffective disorder who were enrolled in a 12-month double-blind clinical trial and randomized to receive either 5 to 20 mg/d of oral olanzapine or haloperidol. Patients were assessed at study entry and at 3, 6 and 12-months on the PANSS and measures of verbal memory, verbal fluency, fine motor coordination, visual sequencing/set shifting, and conceptual reasoning. Functional status was evaluated by the Heinrichs-Carpenter Quality of Life Scale (QLS) and by days of employment in the past 30. Hierarchical regression models examined the association of functional status with symptomatology and three neurocognitive factors (motor skills, memory and card sorting), controlling for demographics and visit number. A mixed effects model was used to adjust for repeated observations from the same subjects.. The PANSS explained 16% additional variance in QLS total score after accounting for demographics and visit number (p<.001), while the neurocognitive factors explained only 4% additional variance beyond the effect of symptoms. When neurocognition was entered before symptoms, it explained an additional 8% of the variance on the QLS total score, while the PANSS explained an additional 12% over and above neurocognition.. These findings suggest that symptoms may pose an equal or greater impediment to functional capacity independent of neurocognition, at least in younger non-institutionalized people with schizophrenia.

Topics: Activities of Daily Living; Administration, Oral; Adult; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Dose-Response Relationship, Drug; Double-Blind Method; Employment; Female; Follow-Up Studies; Haloperidol; Humans; Male; Middle Aged; Neuropsychological Tests; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Quality of Life; Schizophrenia; Schizophrenic Psychology; Social Adjustment; Veterans

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

Primary negative symptoms are intrinsic to the pathology of schizophrenia and are associated with significant deficits in motivation, verbal and nonverbal communication, affect, and cognitive and social functioning. Overall, atypical antipsychotic medications have been found to be more efficacious than conventional antipsychotics in the treatment of negative symptoms, based on studies with acute patients. Results have been confounded by concomitant improvements in positive, depressive, and extrapyramidal symptoms. This 12-week, double-blind, controlled study aimed to examine the effects of the atypical antipsychotic olanzapine versus haloperidol on persistent, primary negative symptoms and neurocognitive functions in stable schizophrenic patients with the deficit syndrome and low levels of concomitant positive, depressive, and extrapyramidal symptoms.. Thirty-five patients with DSM-IV-TR schizophrenia and predominant negative symptoms were randomly assigned in a 12-week double-blind study to either olanzapine (15-20 mg/day) or haloperidol (15-20 mg/day). Patients taking haloperidol received additional blinded benztropine. Inclusion criteria were Positive and Negative Syndrome Scale (PANSS) negative score of >or=20, PANSS positive score < 20, and fulfilling the criteria for the Schedule for the Deficit Syndrome. The PANSS, Clinical Global Impressions, Hamilton Rating Scale for Depression (HAM-D), Simpson-Angus Scale, and Abnormal Involuntary Movement Scale were assessed at regular subsequent intervals. A neuropsychological battery examining declarative verbal learning memory, attention and processing speed, executive functioning, and simple motor functioning domains of cognition was assessed at baseline and endpoint. The study ran from September 1998 through May 2005.. There was a statistically significant difference for PANSS negative symptoms (F = 5.44, df = 1,15; p

Topics: Adult; Affect; Antipsychotic Agents; Attention; Benzodiazepines; Cognition; Cognition Disorders; Communication; Double-Blind Method; Female; Haloperidol; Humans; Male; Middle Aged; Motivation; Olanzapine; Schizophrenia; Social Behavior; Treatment Outcome

To compare olanzapine and risperidone outcome on some neurocognitive dimensions in chronic schizophrenia patients with prominent negative symptoms.. We randomised and followed for 1 year 235 chronic schizophrenia outpatients with a SANS global score > or =10 to open-label flexible-dose treatment with olanzapine or risperidone. Clinical, functional and cognitive assessments [including the COGLAB battery reaction time, vigilance-span of apprehension (VSA) and a card-sorting task] were done periodically.. There were no significant differences between olanzapine (n=120) and risperidone (n=115) treatments in the neurocognitive dimensions tested. Mean+/-SD doses were 12.2+/-5.8 mg/day of olanzapine and 4.9+/-2.0 mg/day of risperidone. Patients in the olanzapine group showed a significant improvement in the VSA total score, but the within-group change was modest (effect size of 0.26); the difference with the risperidone group was not significant (p=0.207). Patients in both groups showed a significant improvement in a composite measure of executive efficiency based on the card-sorting task, with within-group effect size of 0.21 (risperidone) and 0.35 (olanzapine); the between-group difference was not significant (p=0.164). At baseline, better functional status correlated with VSA. Patients scoring lower on VSA or executive efficiency at baseline improved more on these respective measures.. Modest pro-cognitive effects can also be found in chronic schizophrenia outpatients with prominent negative symptoms when treated with olanzapine or risperidone.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neuropsychological Tests; Olanzapine; Outpatients; Pain Measurement; Reaction Time; Risperidone; Schizophrenia; Schizophrenic Psychology; Single-Blind Method; Social Behavior; Spain

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

Although antipsychotic drugs control acute psychotic manifestations of schizophrenia, improving cognitive symptoms is also important for long-term prognosis.. Three hundred and seventy-seven adult patients with acute psychosis were randomised to either amisulpride (200-800 mg/d) or olanzapine (5-20 mg/d) for 6 months. Neuropsychological performance was assessed at inclusion and after 6 months in a subgroup of 26 subjects (11 treated with amisulpride and 15 with olanzapine) using the Auditory Verbal Learning Test (AVLT), the Trail Making Test (TMT) and the Controlled Oral Word Association Test (COWAT).. The improvement in BPRS score was similar in both treatment groups. No significant differences in test performance between groups were observed at inclusion. After 6 months, AVLT scores increased by 8.7 points in the amisulpride group and by 2.3 points in the olanzapine group (p = 0.049). Completion speed in the TMT increased by 17.4 s (amisulpride) and 15.4 s (olanzapine) for Part A and by 39.8 and 48.8 s, respectively for Part B. Performance in the COWAT improved little in both groups.. Both amisulpride and olanzapine produce sustained improvement in certain measures of neuropsychological performance in patients with schizophrenia; a significant improvement in score on the AVLT was observed only with amisulpride.

Topics: Acute Disease; Adult; Amisulpride; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Olanzapine; Prognosis; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Sulpiride

Cognitive impairment in schizophrenia is frequent, involves multiple domains, and is enduring. Numerous recent clinical trials have suggested that second-generation antipsychotic medications significantly enhance cognition in schizophrenia. However, none of these studies included healthy controls undergoing repeated testing to assess the possibility that improvements might reflect simple practice effects.. To report the results on cognition of a randomized comparison of 2 widely prescribed second-generation antipsychotic medications, olanzapine and risperidone, in patients with first-episode schizophrenia and a healthy control group.. Randomized clinical trial.. Hospital-based research units. Patients A total of 104 participants with first-episode schizophrenia and 84 healthy controls.. Cognitive assessment of all study participants occurred at baseline, 6 weeks later, and 16 weeks later. Neurocognitive tests included measures of working memory and attention, speed, motor function, episodic memory, and executive function.. No differential drug effects were observed. Of 16 cognitive measures, 9 demonstrated improvement over time and only 2 demonstrated greater rates of change than those observed in the healthy control group undergoing repeated assessment. The composite effect size for cognitive change was 0.33 in the healthy control group (attributed to practice) and 0.36 in the patients with first-episode schizophrenia. Improvements in cognition in the first-episode schizophrenia group could not be accounted for by medication dose, demographic variables, or intellectual level.. The cognitive improvements observed in the trial were consistent in magnitude with practice effects observed in healthy controls, suggesting that some of the improvements in cognition in the first-episode schizophrenia group may have been due to practice effects (ie, exposure, familiarity, and/or procedural learning). Our results also indicated that differential medication effects on cognition were small. We believe that these findings have important implications for drug discovery and the design of registration trials that attempt to demonstrate cognitive enhancement.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cognition; Cognition Disorders; Control Groups; Female; Humans; Male; Neuropsychological Tests; Olanzapine; Practice, Psychological; Psychiatric Status Rating Scales; Research Design; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Neurocognitive deficits are severe in first-episode psychosis.. Patients (N = 263) with first-episode psychosis (schizophrenia, schizoaffective, or schizophreniform disorders) were randomly assigned to double-blind treatment with olanzapine (mean 11.30 mg/day) or haloperidol (mean 4.87 mg/day) for 104 weeks. A neurocognitive battery was administered at baseline (n = 246) and 12 (n = 167), 24 (n = 126), 52 (n = 89), and 104 (n = 46) weeks during treatment. Weighted principal component and unweighted composite scores were derived from individual tests.. Both treatment groups demonstrated significant improvement on both composite scores. On the basis of the weighted composite score, olanzapine had greater improvement than haloperidol only at 12 (p = .014) and 24 (p = .029) weeks. For the unweighted composite, olanzapine had significantly better improvement compared with haloperidol only at week 12 (p = .044). At week 12 only, olanzapine improved performance on the Digit Symbol and Continuous Performance Test significantly more than haloperidol.. Both antipsychotic agents appeared to improve neurocognitive functioning among first-episode psychosis patients with schizophrenia. A significantly greater benefit in terms of neurocognitive improvement was found with olanzapine than with haloperidol at weeks 12 and 24.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Haloperidol; Humans; Male; Neuropsychological Tests; Olanzapine; Principal Component Analysis; Psychotic Disorders; Statistics, Nonparametric

The authors examined cognitive changes associated with treatment with ziprasidone and olanzapine over a 6-month double-blind clinical trial, using normative standards for the cognitive measures. Sixty-two schizophrenia patients entered the study on ziprasidone treatment (39 completers), and 71 patients entered while receiving treatment with olanzapine (33 completers). From a larger set of cognitive domains assessed in the acute treatment study, we selected verbal learning, executive functioning, and verbal fluency for further analysis due to their functional relevance and extensive normative data. Standard scores were developed based on previously published age- and education-corrected norms. Baseline performance was impaired across all tests on average. The proportion of patients impaired on each of the tests at baseline ranged from 36% (letter fluency) to 89%. Performance was significantly improved by ziprasidone and olanzapine treatment for all cognitive variables and for the composite measure. A number of subjects met the a priori criteria for normalization in performance, ranging from 10% for Trail Making Test Part B to 37% for Word List Total Learning. There were no significant differences across medications in extent of change or likelihood of inducing normalization. Statistically significant improvements in cognitive performance over 6 months of treatment with atypical antipsychotic medications are associated with performance increasing into the normal range of cognitive functioning in a proportion of previously impaired patients.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Double-Blind Method; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Olanzapine; Patient Admission; Piperazines; Psychometrics; Psychotic Disorders; Schizophrenia; Thiazoles

We report here a study examining the relationships between insight and psychopathology, cognitive performance, brain volume and co-morbid depression in 251 patients experiencing a first episode of psychosis, who were then randomly assigned to 2 years of double-blind treatment with either olanzapine or haloperidol.. Repeated measures of insight were obtained at baseline and 12, 24, 52 and 104 weeks by the Insight and Treatment Attitudes Questionnaire (ITAQ).. Older age, female gender and white ethnicity were associated with more insight. Higher total, positive, negative and general psychopathology scores on the Positive and Negative Syndromes Scale (PANSS) were associated with less insight. Higher depression scores were associated with more insight. Better neurocognitive function and large brain volumes were associated with more insight. More insight throughout the study was associated with longer time to medication non-adherence. However, baseline insight was not significantly related to the probability of discontinuing the study before 2 years. Insight improved significantly over the course of the study, but the improvement in insight was not significantly different between the two antipsychotic treatment groups.. Multiple factors contribute to insight. Patients experiencing a first episode of psychosis who have little insight are at increased risk of discontinuing their medication.

Topics: Adolescent; Adult; Antipsychotic Agents; Attitude to Health; Benzodiazepines; Brain; Cognition Disorders; Depressive Disorder, Major; Double-Blind Method; Female; Haloperidol; Humans; Male; Neuropsychological Tests; Olanzapine; Psychotic Disorders; Surveys and Questionnaires; Treatment Refusal

Recovery from anorexia nervosa is confounded by intrusive anorectic cognitions and rituals. It has been observed that olanzapine, an atypical antipsychotic, can reduce this anorexic rumination. A pilot study was designed to test the effectiveness of olanzapine in this role.. A randomized trial of olanzapine versus chlorpromazine, with anorexic rumination as the primary outcome, was conducted. Of the 26 patients who presented, 15 were randomized in a balanced block design, eight to olanzapine and seven to chlorpromazine.. Only the olanzapine group had a significant reduction in the degree of rumination.. Olanzapine may be of benefit in anorexia nervosa by causing a reduction in anorexic rumination.

Topics: Adult; Anorexia Nervosa; Antipsychotic Agents; Benzodiazepines; Chlorpromazine; Cognition Disorders; Drug Administration Schedule; Female; Humans; Male; Olanzapine

Pathomorphologic brain changes occurring as early as first-episode schizophrenia have been extensively described. Longitudinal studies have demonstrated that these changes may be progressive and associated with clinical outcome. This raises the possibility that antipsychotics might alter such pathomorphologic progression in early-stage schizophrenia.. To test a priori hypotheses that olanzapine-treated patients have less change over time in whole brain gray matter volumes and lateral ventricle volumes than haloperidol-treated patients and that gray matter and lateral ventricle volume changes are associated with changes in psychopathology and neurocognition.. Longitudinal, randomized, controlled, multisite, double-blind study. Patients treated and followed up for up to 104 weeks. Neurocognitive and magnetic resonance imaging (MRI) assessments performed at weeks 0 (baseline), 12, 24, 52, and 104. Mixed-models analyses with time-dependent covariates evaluated treatment effects on MRI end points and explored relationships between MRI, psychopathologic, and neurocognitive outcomes.. Fourteen academic medical centers (United States, 11; Canada, 1; Netherlands, 1; England, 1).. Patients with first-episode psychosis (DSM-IV) and healthy volunteers.. Random allocation to a conventional antipsychotic, haloperidol (2-20 mg/d), or an atypical antipsychotic, olanzapine (5-20 mg/d).. Brain volume changes assessed by MRI.. Of 263 randomized patients, 161 had baseline and at least 1 postbaseline MRI evaluation. Haloperidol-treated patients exhibited significant decreases in gray matter volume, whereas olanzapine-treated patients did not. A matched sample of healthy volunteers (n = 58) examined contemporaneously showed no change in gray matter volume.. Patients with first-episode psychosis exhibited a significant between-treatment difference in MRI volume changes. Haloperidol was associated with significant reductions in gray matter volume, whereas olanzapine was not. Post hoc analyses suggested that treatment effects on brain volume and psychopathology of schizophrenia may be associated. The differential treatment effects on brain morphology could be due to haloperidol-associated toxicity or greater therapeutic effects of olanzapine.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Brain; Caudate Nucleus; Cognition Disorders; Female; Haloperidol; Humans; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Olanzapine; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

This was an exploratory study of olanzapine as potential treatment for improvement in cognition in patients with Alzheimer's disease without prominent psychobehavioral symptoms.. Non-psychotic/non-agitated patients (n = 268) with Alzheimer's disease, who had baseline Mini-Mental State Examination (MMSE) scores of 14-26 were randomized to treatment with olanzapine (2.5 to 7.5 mg/d) or placebo for 26 weeks. The primary objectives were to determine if treatment with olanzapine improved cognition as indexed by the Alzheimer's disease Assessment Scale for Cognition (ADAS-Cog) and the Clinician's Interview-Based Impression of Change (CIBIC) after 26 weeks of therapy.. Patients treated with olanzapine vs placebo experienced significant worsening ADAS-Cog scores at weeks 12 (p = 0.03) and 26 (p = 0.004). Changes in CIBIC scores were not significantly different between treatment groups at either assessment. A post hoc analysis revealed that olanzapine-treated patients with more cognitive impairment at baseline (MMSE scores of 14-18) (n = 35) experienced significantly greater deterioration in ADAS-Cog performance than patients in the placebo group (n = 24; p < 0.001); whereas in patients with less cognitive impairment (n = 78, baseline MMSE scores of 23-26) between-group ADAS-Cog changes were not significant.. In this 26-week study non-psychotic/non-agitated patients with Alzheimer's disease treated with olanzapine experienced significant worsening of cognition as compared to placebo.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Disease Progression; Double-Blind Method; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Olanzapine; Prospective Studies; Psychiatric Status Rating Scales; Psychomotor Agitation; Treatment Outcome

Psychotic symptoms and behavioral disturbances are a concern in the care of elderly patients with Alzheimer's dementia (AD). This study was conducted to compare the efficacy of olanzapine versus placebo in patients with psychotic symptoms associated with AD in long-term or continuing-care settings.. Patients (n = 652) with AD and delusions or hallucinations were randomly assigned to 10 weeks of double-blind treatment with placebo or fixed-dose olanzapine (1.0, 2.5, 5.0, 7.5 mg/day).. Mean age was 76.6+/-10.4 years. Repeated-measures analysis showed significant improvement from baseline in NPI/NH Psychosis Total scores (sum of Delusions, Hallucinations items-primary efficacy measure) in all five treatment groups (p<0.001), but no pairwise treatment differences were seen at the 10-week endpoint. However, under LOCF analysis, improvement in the 7.5 mg olanzapine group (-6.2 +/- 4.9) was significantly greater than with placebo (-5.0 +/- 6.1, p = 0.008), while endpoint CGI-C scores showed the greatest improvement in the Olz 2.5 olanzapine group (2.8 +/- 1.4, p = 0.030) relative to placebo (3.2 +/- 1.4). There were significant overall treatment-group differences in increased weight, anorexia, and urinary incontinence, with olanzapine showing numerically higher incidences. However, neither the incidence of any other individual events, including extrapyramidal symptoms, nor of total adverse events occurred with significantly higher frequency in any olanzapine group relative to placebo. No clinically relevant significant changes were seen across groups in cognition or any other vital sign or laboratory measure, including glucose, triglyceride, and cholesterol.. While 1.0 mg olanzapine did not show significant differences from placebo, the 2.5 mg dose was a reasonable starting dose. Olanzapine at 7.5 mg/day significantly decreased psychosis and overall behavioral disturbances (NPI/NH, BPRS) and was well tolerated.

Topics: Adult; Aged; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Delusions; Double-Blind Method; Female; Hallucinations; Humans; Male; Middle Aged; Olanzapine; Patient Compliance; Psychiatric Status Rating Scales; Psychotic Disorders; Time Factors; Treatment Outcome

The effect of antipsychotic medication on neurocognitive function remains controversial, especially since most previous work has compared the effects of novel antipsychotic medications with those of high doses of conventional medications. This study compares the neurocognitive effects of olanzapine and low doses of haloperidol in patients with first-episode psychosis.. Patients with a first episode of schizophrenia, schizoaffective disorder, or schizophreniform disorder (N=167) were randomly assigned to double-blind treatment with olanzapine (mean modal dose= 9.63 mg/day) or haloperidol (mean modal dose=4.60 mg/day) for the 12-week acute phase of a 2-year study. The patients were assessed with a battery of neurocognitive tests at baseline and 12 weeks after beginning treatment.. An unweighted neurocognitive composite score, composed of measures of verbal fluency, motor functions, working memory, verbal memory, and vigilance, improved significantly with both haloperidol and olanzapine treatment (effect sizes of 0.20 and 0.36, respectively, no significant difference between groups). A weighted composite score developed from a principal-component analysis of the same measures improved to a significantly greater degree with olanzapine, compared with haloperidol. Anticholinergic use, extrapyramidal symptoms, and estimated IQ had little effect on the statistical differentiation of the medications, although duration of illness had a modest effect. The correlations of cognitive improvement with changes in clinical characteristics and with side effects of treatment were significant for patients who received haloperidol but not for patients who received olanzapine.. Olanzapine has a beneficial effect on neurocognitive function in patients with a first episode of psychosis. However, in a comparison of the effects of olanzapine and low doses of haloperidol, the difference in benefit is small.

Topics: Adolescent; Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Cognition Disorders; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Haloperidol; Humans; Male; Neuropsychological Tests; Olanzapine; Principal Component Analysis; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

The main objective of this study was to compare 1-year outcome on symptoms, extrapyramidal side effects (EPS) , positive and negative symptoms, and domains of cognition in first episode psychosis (FEP) patients. Drug-naive FEP patients, who were similar on a number of characteristics likely to affect outcome, were treated with only one antipsychotic (risperidone or olanzapine) for at least 1 year and compared at baseline and after 1 year of treatment. Differences in outcome were assessed using an analysis of co-variance with change scores between initial assessment and after 1 year of treatment on levels of psychotic, disorganization and psychomotor poverty symptoms, EPS (parkinsonism, akathesia and dyskineisa) and domains of cognition as the dependent variable, respective baseline scores as covariates, and drug group as the independent variable. While patients in both groups showed substantial improvement, there were no significant differences in the magnitude of change in reality distortion, disorganization and psychomotor poverty symptoms. Trends in change in EPS favouring olanzapine and on some domains of cognition (processing speed and executive functions) favouring risperidone failed to reach statistical significance. The failure to confirm previous claims of greater improvement on either risperidone or olanzapine in patients with a first episode of psychosis may be the result of methodological bias introduced by unequal dosing between the two drugs or the use of chronically ill and treatment-refractory patients in previous studies.

Topics: Adolescent; Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Cognition Disorders; Female; Humans; Male; Olanzapine; Psychomotor Disorders; Psychotic Disorders; Risperidone; Severity of Illness Index

Older individuals with dementia are highly sensitive to the effects of muscarinic receptor blockade.. This was a 6-week multisite, randomized clinical trial.. Eighty-six patients with probable Alzheimer's disease, vascular dementia, or mixed-etiology dementia (DSM-IV criteria) were randomly assigned to treatment with olanzapine or risperidone.. Anticholinergic activity was measured with a radioreceptor assay, and plasma levels of antipsychotic medications were determined. Primary outcomes were assessed with the Udvalg for Kliniske Undersogelser (UKU) scale and somnolence adverse events; secondary outcome measures included scores on the Neuropsychiatric Inventory (NPI) and other scales.. There were no between-treatment differences in the UKU scale or in somnolence adverse events. Statistically significant improvements (p < .001) from baseline were found for the NPI measures, with no between-treatment group differences. Olanzapine was associated with significant increases from baseline in anticholinergic activity, while risperidone was not; the between-treatment group differences were not statistically significant. Increase in anticholinergic activity was associated with an increase in anticholinergic side effects and slower performance on the Trail Making Test Part A. Higher endpoint anticholinergic activity was associated with higher endpoint scores on several items from the NPI, including delusions, anxiety, and aberrant motor behavior.. Efficacious doses of olanzapine increased anticholinergic activity in older patients with dementia, while similarly efficacious doses of risperidone did not. Patients whose anticholinergic activity increased were more likely to experience anticholinergic side effects and to have worsening in certain cognitive domains. These data suggest that certain patients may be vulnerable to the anticholinergic activity associated with antipsychotic treatment.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Cognition Disorders; Delusions; Dementia; Double-Blind Method; Female; Hallucinations; Humans; Male; Middle Aged; Muscarinic Antagonists; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Radioligand Assay; Receptors, Muscarinic; Risperidone; Sleep Wake Disorders; Trail Making Test; Treatment Outcome

A pilot study was conducted to examine if donepezil could enhance cognitive function in patients with schizophrenia. Fifteen subjects who were on stable olanzapine treatment were entered into a 6-week open-labeled trial of donepezil. Subjects received baseline and end-of-study P50 and neuropsychological assessments. Donepezil treatment resulted in significant improvement in manual dexterity. There were moderate improvements in verbal recall memory and visual memory and processing speed, with smaller changes in P50 and verbal recognition memory. There was no effect on an attention measure. There were no changes in either positive or negative symptoms. These results suggest that cholinergic tone modulation may enhance selective behavioral functions in patients with schizophrenia, but further study is required to delineate the full extent of the potential benefit of this approach.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Donepezil; Drug Therapy, Combination; Evoked Potentials; Female; Humans; Indans; Male; Memory; Nootropic Agents; Olanzapine; Pilot Projects; Piperidines; Pirenzepine; Schizophrenia

The effects of risperidone and olanzapine on cognitive functioning in patients with schizophrenia were compared in a randomized, double-blind trial.. Three hundred and seventy-seven patients were randomly assigned to receive 2-6 mg/day of risperidone or 5-20 mg/day of olanzapine for 8 weeks. Cognitive function was assessed with a focused cognitive assessment battery; in addition, extrapyramidal symptoms were assessed using the extrapyramidal symptom rating scale (ESRS), and the positive and negative syndrome scale (PANSS) was rated for all patients.. Treatment with these two atypical antipsychotic medications was associated with improved performance on the Wisconsin card sorting test, the trail-making test, the California verbal learning test, the continuous performance test, and some aspects of verbal fluency and spatial working memory. No differences in the effects of the drugs on any of the cognitive tests were noted. Correcting for the effects of anticholinergic treatment did not alter the magnitude of cognitive effects.. Atypical antipsychotic treatment is associated with wide-ranging benefits on cognitive functioning. Previous reports of greater benefits of olanzapine over risperidone in a small-sample pilot study were not substantiated. These results are not due in general to changes in clinical symptoms or movement disorders, suggesting a direct effect of atypical antipsychotic medications on cognitive deficits in schizophrenia.

Topics: Adolescent; Adult; Arousal; Benzodiazepines; Cognition Disorders; Diagnostic and Statistical Manual of Mental Disorders; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Memory, Short-Term; Middle Aged; Movement Disorders; Olanzapine; Pirenzepine; Psychomotor Performance; Risperidone; Schizophrenia; Selective Serotonin Reuptake Inhibitors; Serotonin Antagonists; Verbal Learning

Atypical antipsychotics are the first-line treatment for psychosis and are commonly used for behavioural problems in people with intellectual disabilities (ID), but a comprehensive evidence base for this approach is lacking. We studied prescription trends and the clinical effectiveness of risperidone and olanzapine in people with ID in a clinical, naturalistic setting. The results suggest that both drugs are well tolerated and effective in treating target symptoms across a range of diagnoses and ID. Both risperidone and olanzapine appear to reach full efficacy within 3 months, after which improvement reaches a plateau, as reflected in the Clinical Global Impression-Improvement scale. Compliance with both drugs is high. Olanzapine tended to be prescribed mostly for psychotic disorders, and showed good rates of response, whereas risperidone was prescribed mostly for people with behavioural disturbance associated with a psychiatric diagnosis. Furthermore, approximately one-quarter of the risperidone group were prescribed the medication for a behavioural disorder associated with a pervasive developmental disorder. Again, the medication was broadly effective in treatment. Both medications were also used to effectively treat affective disorders in a small percentage of patients. This study appears to indicate that both medications could be of significant clinical benefit for people with ID across a wide range of diagnoses and level of ID, although further controlled trials are required.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Comorbidity; Disabled Persons; Female; Humans; Male; Middle Aged; Mood Disorders; Olanzapine; Pirenzepine; Practice Patterns, Physicians'; Psychotic Disorders; Risperidone; Treatment Outcome

To examine the effects of risperidone and olanzapine on cognitive functioning in elderly patients with schizophrenia or schizoaffective disorder.. One hundred seventy-six elderly inpatients and outpatients with schizophrenia or schizoaffective disorder were enrolled in this multicenter, double-blind trial. After their antipsychotic medications were tapered for 1 week, patients were randomly assigned to receive either risperidone 1 to 3 mg/day or olanzapine 5 to 20 mg/day for 8 weeks. Performance on the Continuous Performance Test (CPT), Serial Verbal Learning Test (SVLT), TMT (Trail Making Test) Parts A and B, Wisconsin Card Sorting Test (WCST), and Verbal Fluency Examinations (VFE) was assessed at baseline and at end point.. Patients in the risperidone group had improved scores on at least one test of attention, memory, executive function, and verbal fluency, and those in the olanzapine group had improved scores on at least one test of attention and memory function. Scores on the TMT Part B, WCST total errors (executive function domain), and the VFE improved significantly from baseline in the risperidone group but not in the olanzapine group. No significant differences in change scores between the two groups were found. Higher baseline scores on each test predicted more improvement at endpoint.. Low doses of risperidone and olanzapine improve cognitive function in elderly patients with schizophrenia or schizoaffective disorder. Consistent with research in younger populations, these improvements occur in aspects of cognitive functioning related to functional outcome.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Double-Blind Method; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Olanzapine; Pirenzepine; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Atypical antipsychotic medications with lower affinities for D2 receptors are considered useful alternatives to treat drug-induced hallucinations in Parkinson's disease (PD). We conducted a double-blind, placebo-controlled, unforced titration, parallel design study (2:1 drug to placebo randomization ratio) using olanzapine (2.5-10 mg/day to effect) in 30 PD patients with drug-induced hallucinations. We performed an extensive battery of neuropsychological tests, the Unified Parkinson's Disease Rating Scale (UPDRS), assessments of on and off time at baseline and at 9 weeks after starting the medication. Sixteen patients on olanzapine (mean dose, 4.6 mg/night) and 11 on placebo completed the study. Compared with placebo, performance on the UPDRS item 2 (thought disorder), and a structured interview for hallucinations, both tended to improve on drug but neither reached statistical significance. A neuropsychological test battery did not show any significant differences. Total on UPDRS motor scores (P < 0.05) and timed tapping (P < 0.01) worsened while on drug compared to placebo. Bradykinesia (P < 0.01) and gait (P < 0.001) items on the UPDRS largely accounted for this deterioration. After completion of the study, 8 of 16 patients randomly assigned to drug continued olanzapine at a mean dose of 2.4 mg/day. However, at the last recorded visit only 5 of 24 (20.8%) of all patients exposed to drug (including those originally randomly assigned to placebo) remained on olanzapine. In patients with PD, low-dose olanzapine did not significantly improve hallucinations but did worsen motor function.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Dopamine Agonists; Double-Blind Method; Female; Hallucinations; Humans; Interview, Psychological; Male; Neuropsychological Tests; Olanzapine; Parkinson Disease; Pirenzepine

Recent studies suggest that novel antipsychotics have positive effects on certain cognitive functions in schizophrenia. The present study investigated this claim by means of saccadic paradigms, which provide a selective index of cognitive function. Thirty-three first-episode schizophrenic patients were randomly assigned to either olanzapine or risperidone treatment and compared with healthy control subjects for three saccadic paradigms. The influence of symptom profile, extrapyramidal symptoms, age, education, gender, hospitalization, and medication dose on cognitive performance was also investigated. Although the two patient groups did not differ from each other in task performance, both patient groups showed substantial problems in inhibitory control of saccades. A high level of education appeared to be protective for this impairment.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Female; Humans; Male; Middle Aged; Olanzapine; Photic Stimulation; Pirenzepine; Risperidone; Saccades; Schizophrenia

Previous research has suggested that high doses of conventional neuroleptics may induce neurocognitive deficits when assessed with standard tasks. However, little is known about the effects of high doses of neuroleptics (conventional or atypical) on subjective cognitive dysfunction. Recent research stresses the putative importance of self-reported cognitive deficits for both symptomatic outcome and medication compliance. The aim of the present study was to investigate the impact of neuroleptic medication on subjective cognition in patients treated with either conventional or atypical agents (clozapine, risperidone, olanzapine). Patients were asked to endorse the items of a questionnaire entitled 'Subjective Well-Being under Neuroleptic Treatment' prior to discharge. Subjective impairment, as assessed with the subscale 'mental functioning', was significantly correlated with greater conventional neuroleptic dosage after controlling for psychopathology (P<0.05). The difference between patients medicated with higher doses of conventional neuroleptics and those with lower doses was highly significant (P<0.001). In contrast, higher atypical neuroleptic doses were not associated with impairment.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Cognition Disorders; Dose-Response Relationship, Drug; Female; Humans; Male; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Risperidone; Schizophrenia; Schizophrenic Psychology; Surveys and Questionnaires

Cognitive impairment in multiple domains is common in patients with schizophrenia and may be a powerful determinant of poor functional ability and quality of life. We report a double-blind, placebo-controlled, cross-over study of donepezil augmentation in a schizoaffective disorder patient stabilized on olanzapine pharmacotherapy. The patient showed significant improvements in several cognitive measures and increased activation of prefrontal cortex and basal ganglia on functional MRI during the donepezil augmentation. In addition, the donepezil augmentation resulted in a reduction of depressive symptoms and in significant improvements in functional abilities and quality of life. Further studies of donepezil augmentation of neuroleptics in schizophrenia are warranted.

Topics: Adult; Basal Ganglia; Benzodiazepines; Brain; Brain Mapping; Cognition Disorders; Cross-Over Studies; Donepezil; Double-Blind Method; Drug Therapy, Combination; Humans; Indans; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Olanzapine; Piperidines; Pirenzepine; Prefrontal Cortex; Psychiatric Status Rating Scales; Psychotic Disorders; Quality of Life

According to current theories, schizophrenia results from altered connectivity in brain circuits for fundamental cognitive operations. Consequently, the poorly understood mechanisms of neuroleptic treatment may be explainable by altered functional interactions within such networks. The 'cognitive dysmetria' model hypothesizes that one key structure in these circuits is the cerebellum. To investigate the effects of olanzapine on cerebellar functional connectivity (CFC), a seed-voxel correlation analysis (SVCA) was used in a functional magnetic resonance imaging (fMRI) study of a simple finger-tapping task.. fMRI scans were obtained from six schizophrenic patients under both drug-free and olanzapine-treated conditions and from a matched control group of six healthy subjects at corresponding time points. SVCAs were performed for anatomically and functionally standardized seed voxels in the anterior cerebellum. SVCA results were then processed by three different randomization analyses.. The analyses revealed that olanzapine caused widespread changes of CFC, including prominent changes in prefrontal cortex and mediodorsal thalamus. Significant changes in motor structures were found after subtractions within both groups and may thus indicate repetition effects rather than drug effects. Olanzapine 'normalized' the patients' CFC patterns for the right, but not for the left cerebellum.. Even for a simple motor task, olanzapine affects functional interactions between the cerebellum and many non-motor brain regions, including elements of the 'cognitive dysmetria' circuit. Altogether, our findings suggest that olanzapine has a stronger differential effect on neural activity in prefrontal cortex and thalamus than in motor structures.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cerebellum; Cognition Disorders; Female; Humans; Magnetic Resonance Imaging; Male; Nerve Net; Neuropsychological Tests; Olanzapine; Pirenzepine; Prefrontal Cortex; Schizophrenia; Severity of Illness Index

The purpose of this investigation was to test the efficacy of novel antipsychotic medications in the treatment of cognitive impairment in early phase schizophrenia.. Sixty-five patients in this multicenter double-blind study were randomly assigned to olanzapine (5-20 mg), risperidone (4-10 mg), or haloperidol (5-20 mg). Standard measures of clinical and motor syndromes were administered, as well as a comprehensive battery of tests to assess (1) motor skills, (2) attention span, (3) verbal fluency and reasoning, (4) nonverbal fluency and construction, (5) executive skills, and (6) immediate recall at baseline and after 6, 30, and 54 weeks of treatment.. The general cognitive index derived from the 6 domain scores revealed a significantly greater benefit from treatment with olanzapine relative to haloperidol and olanzapine relative to risperidone, but no significant difference was shown between risperidone and haloperidol. The improvement related to olanzapine was apparent after 6 weeks and enhanced after 30 and 54 weeks of treatment. Exploratory within-group analyses of the 6 cognitive domains after a conservative Bonferroni adjustment revealed a significant improvement with olanzapine only on the immediate recall domain, and similar analyses of the 17 individual tests revealed a significant improvement with olanzapine only on the Hooper Visual Organization Test.. These data suggest that olanzapine has some superior cognitive benefits relative to haloperidol and risperidone. A larger sample replication study is necessary to confirm and generalize the observations of this study and begin evaluation of the implications of this change to cerebral function and quality of life for people with schizophrenia.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Double-Blind Method; Female; Haloperidol; Humans; Male; Middle Aged; Motor Skills; Neuropsychological Tests; Olanzapine; Pirenzepine; Psychomotor Performance; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Depressive symptoms are common during the course of schizophrenia and may carry prognostic relevance.. From a 28-week prospective, double-blind, randomized study of olanzapine and risperidone, a post hoc evaluation of changes on the Positive and Negative Syndrome Scale (PANSS) depression cluster (PDC) and the subsequent risk of relapse were analyzed by logistic regression.. Olanzapine was associated with a significantly higher categorical rate of improvement on the PANSS depression cluster (> or = 7 points) (p < .05). Although the baseline severity of depressive symptoms was not a significant predictor of relapse, the degree of acute (8-week) mood improvement on the PANSS depression cluster (but neither negative or positive symptom changes) was related to the probability of a subsequent psychotic relapse. Acute mood improvement with olanzapine was inversely related to a nonsignificantly lower risk of relapse. However, an opposite and significant relationship was observed among risperidone-treated subjects. Risperidone-treated subjects with a greater degree of acute mood change were both 3.58 times more likely to relapse than their risperidone counterparts who had experienced less mood improvement (p = .008) and 8.55 times more likely than olanzapine-treated subjects who had had similar mood improvements (p = .001).. These data suggest the underlying pharmacologic differences between the two drugs may bestow different rates of longer-term mood stabilization and relapse prevention. In a second series of analyses, worsening on the PANSS depression cluster in the 4 weeks or less preceding a clinical relapse was a significant prodromal predictor of relapse among all subjects. As a whole, subjects with a worsening on the PDC demonstrated a 1.77 times higher risk of a relapse during the subsequent 4 weeks (p = .001). Among this mood-worsening stratum, risperidone-treated patients were 3.51 times more likely to relapse in those next 4 weeks (p = .005) than their olanzapine counterparts. Future comparative drug studies in this area will further contribute to our understanding of the pathophysiology of mood change and its relationship to psychosis, including clinical relapse and how newer agents may differ in their respective delivery of long-term treatment outcomes.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cluster Analysis; Cognition Disorders; Depressive Disorder; Double-Blind Method; Female; Humans; Male; Neuropsychological Tests; Olanzapine; Pirenzepine; Prognosis; Prospective Studies; Recurrence; Regression Analysis; Risperidone; Schizophrenia; Schizophrenic Psychology

Alzheimer's disease (AD) is a profoundly debilitating neurodegenerative disorder characterized most notably by progressive cognitive decline, but also agitation and behavioral disturbances that are extremely disruptive to patient and caregiver. Current pharmacological treatments for these symptoms have limited efficacy and significant side effects. We have recently reported the discovery of Compound 24, an M4 positive allosteric modulator (PAM) that is potent, highly selective, and devoid of cholinergic-like side effects in rats. In order to further evaluate the translatability of the effects of compound 24 in primates, here we describe the effect of Compound 24 on three behavioral and cognition assays in rhesus monkeys, the stimulant induced motor activity (SIMA) assay, the object retrieval detour task (ORD), and the visuo-spatial paired-associates learning (vsPAL) task. As far as we know, this is the first such characterization of an M4 PAM in non-human primate. Compound 24 and the clinical standard olanzapine attenuated amphetamine induced hyperactivity to a similar degree. In addition, Compound 24 demonstrated procognitive effects in scopolamine-impaired ORD and vsPAL, and these effects were of similar magnitude to donepezil. These findings suggest that M4 PAMs may be beneficial to diseases such as Alzheimer's disease and schizophrenia, which are marked by behavioral disturbances as well as deficits in cognitive function.

Topics: Alzheimer Disease; Amphetamine; Animals; Association Learning; Behavior, Animal; Central Nervous System Stimulants; Cholinergic Agents; Cognition Disorders; Hyperkinesis; Macaca mulatta; Male; Motor Activity; Olanzapine; Orientation; Receptor, Muscarinic M4; Schizophrenia; Schizophrenic Psychology

It is generally accepted that impaired cognitive function is a core feature of schizophrenia. There is evidence for the role of brain-derived neurotrophic factor (BDNF) in cognitive function. Olanzapine was reported to yield cognitive improvement in patients with schizophrenia.. In this study, we performed a prospective, open-label, 12-week observation trial to investigate whether peripheral BDNF may represent a potential biomarker for the effect of cognitive improvement induced by olanzapine in patients with schizophrenia.. In total, 95 patients with acute schizophrenia were enrolled in the study. We also recruited 72 healthy individuals for a control group. The Positive and Negative Syndrome Scale (PANSS) was used to evaluate symptom severity and treatment response. Cognitive function was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Plasma BDNF levels were measured with an enzyme-linked immunosorbent assay.. Of the 95 patients consented into the study, 68 completed the 12-week follow up. Our results showed that schizophrenia patients with acute exacerbation had significantly poorer performance than that of the controls (Ps < 0.01). A significantly decreased plasma level of BDNF in patients was observed compared with the controls (F = 7.77, P = 0.006). A significant improvement in each PANSS subscore and total score was observed when the patients completed this study (Ps < 0.01). Additionally, 12-week olanzapine treatment exhibited significant improvements in RBANS immediate memory, attention, and total scores (P = 0.018, 0.001, and 0.007, respectively). Along with the clinical improvement, plasma BDNF levels after 12-week olanzapine monotherapy (4.67 ± 1.74 ng/ml) were also significantly increased compared with those at baseline (3.38 ± 2.11 ng/ml) (P < 0.01). Spearman's correlation analysis showed that the increase in plasma levels of BDNF is significantly correlated with the change in the RBANS total scores (r = 0.28, P = 0.02) but not with the change in the PANSS total scores (r = - 0.18, P = 0.13). There is a significant correlation of BDNF increase with the change of RBANS attention subscore (r = 0.27, P = 0.028).. Our findings suggest that olanzapine improves psychiatric symptoms and cognitive dysfunction, particularly attention and immediate memory, in patients with acute schizophrenia, in parallel with increased plasma BDNF levels. Plasma BDNF levels may be a potential biomarker for cognitive recovery in acute schizophrenia.

Topics: Adult; Antipsychotic Agents; Biomarkers; Brain-Derived Neurotrophic Factor; Cognition; Cognition Disorders; Female; Humans; Longitudinal Studies; Male; Memory, Short-Term; Middle Aged; Olanzapine; Prospective Studies; Schizophrenia; Young Adult

Topics: Antipsychotic Agents; Benzodiazepines; Cognition; Cognition Disorders; Humans; Olanzapine; Risperidone; Schizophrenia

Diacylglycerol kinase (DGK) is an enzyme that converts diacylglycerol to phosphatidic acid. Previously, we reported that DGKβ knockout (KO) mice showed mania-like behaviors such as hyperactivity, reduced anxiety, and cognitive impairment. Furthermore, lithium ameliorated the hyperactivity and reduced anxiety of DGKβ KO mice. In this study, we investigated the effects of the clinically active antimanic drugs valproate and olanzapine on the abnormal behaviors of DGKβ KO mice.. Valproate (100mg/kg/day) and olanzapine (1mg/kg/day) were administered intraperitoneally. Following drugs treatments, behavioral tests were performed to investigate locomotor activity, anxiety levels, and cognitive function of the mice.. A single treatment of valproate and olanzapine did not ameliorate the hyperactivity or abnormal anxiety level of DGKβ KO mice. Chronic treatment with valproate and olanzapine significantly decreased locomotor activity and abnormal anxiety levels of DGKβ KO mice. Additionally, valproate also ameliorated cognitive function of DGKβ KO mice.. These results suggest that the abnormal behaviors of DGKβ KO mice is responsive to antimanic drugs, and that DGKβ KO mice are useful as an animal model of mania.

Topics: Animals; Anxiety; Benzodiazepines; Cognition Disorders; Diacylglycerol Kinase; Disease Models, Animal; Drug Therapy, Combination; Male; Maze Learning; Mice; Mice, Knockout; Motor Activity; Olanzapine; Valproic Acid

The aim of the study was to explore the effects of increased levels of blood sugar and cytokines on impaired cognitive function in the olanzapine-induced obesity rat model. A total of 40 rats were randomly divided into 2 groups; the control and olanzapine groups (N = 20 per group). The control rats were fed regular food, while the olanzapine rats received olanzapine-enriched (1.2 mg/kg) food by gavage for 4 weeks to establish the olanzapine-induced obese rat model. Enzyme-linked immunosorbent assays were used to measure the serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP). Serum glucose content was measured by biochemical colorimetry. Learning and memory capacity was measured using a Y-maze, and the time before escape from a Morris water maze was recorded. Body weight and levels of blood glucose, lipids, TNF-α, IL-6, and CRP increased in the olanzapine group. In addition, the number of shocks received before reaching the learning and memory standard and the time before escape from the Morris water maze were higher in the olanzapine group than in the control group. Olanzapine causes disorders in glucose and lipid metabolism. Increase in blood glucose promotes the toxicity of cytokines and leads to cognitive dysfunction in rats.

Topics: Animals; Benzodiazepines; Blood Glucose; Body Weight; C-Reactive Protein; Cognition Disorders; Disease Models, Animal; Interleukin-6; Lipid Metabolism; Lipids; Memory; Obesity; Olanzapine; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

Schizophrenia patients exhibit a wide range of impairments in cognitive functions. Clinically, atypical antipsychotic drugs (AAPs) such as olanzapine (OLZ) have a therapeutic effect on memory function among schizophrenia patients rather than typical antipsychotics, e.g., haloperidol. To date, however, little is known about the neuroplasticity mechanism underlying the effect of AAPs on the impairment of cognitive functions. Here, we treated schizophrenia rat models with a systematic injection of MK-801 (0.1mg/kg) and chose the drug OLZ as a tool to investigate the mechanisms of AAPs when used to alter cognitive function. The results showed that the systematic administration of MK-801 results in the impairment of spatial learning and memory as well as spatial working memory in a Morris water maze task. OLZ but not HAL improved these MK-801-induced cognitive dysfunctions. After MK-801 application, the hippocampal LTP was profoundly impaired. In conjunction with the results of the behavioral test, the administration of OLZ but not of HAL resulted in a significant reversal effect on the impaired LTP induced via MK-801 application. Furthermore, we found that OLZ but not HAL can upregulate the phosphorylation of GluR1 Ser845. These data suggest that the therapeutic effect of OLZ on cognitive dysfunctions may be due to its contribution to synaptic plasticity via the ability to upregulate the state of GluR1 Ser845 phosphorylation. We therefore suggest that the upregulated state of GluR1 Ser845 phosphorylation may be a promising target for developing novel therapeutics for treating schizophrenia.

Topics: Animals; Antipsychotic Agents; Behavior, Animal; Benzodiazepines; Cognition Disorders; Disease Models, Animal; Dizocilpine Maleate; Excitatory Amino Acid Antagonists; Haloperidol; Hippocampus; Male; Memory, Short-Term; Neuronal Plasticity; Olanzapine; Phosphorylation; Rats; Rats, Sprague-Dawley; Receptors, AMPA; Schizophrenia; Spatial Learning

Schizophrenia is a group of mental disorders of unclear origin, affecting around 1% of global population, most commonly young people. Of various treatment methods, pharmacotherapy using atypical neuroleptics such as aripiprazole (ARI) and olanzapine (OLA) seems to be the most effective. The aim of this paper was to show that prenatal stress causes impairment of cognitive functions in adolescent rats.. The effect of chronic stress used in pregnant rats and the use of drugs such as ARI (1.5 mg/kg) and OLA (0.5 mg/kg) were studied in the Morris Water Maze (spatial memory) and Porsolt test (antidepressant effect).. The behavioral tests showed that ARI improved spatial memory both in the non-stressed control group (NSCG) (after single and chronic treatment) and in the prenatally stressed group (PSG) (only in 14 and 21 days of treatment). An antidepressant effect was observed in the NSCG (only in 1 and 7 days) and the PSG (after single and chronic administration). OLA also showed memory improvement in the NSCG (chronic treatment - 14 and 21 days) and the PSG (all days of treatment) rats, but the antidepressant effect was noted only in single administration in both study groups (NSCG and PSG).. Results suggest that ARI and OLA may prove effective in treating both schizophrenia and depression and may improve disturbed memory functions observed in these diseases.

Topics: Animals; Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Behavior, Animal; Benzodiazepines; Cognition Disorders; Depression; Disease Models, Animal; Drug Administration Schedule; Female; Male; Maze Learning; Memory Disorders; Olanzapine; Piperazines; Pregnancy; Prenatal Exposure Delayed Effects; Quinolones; Rats; Rats, Wistar; Schizophrenia; Stress, Psychological; Time Factors

Topics: Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Female; Humans; Male; Molindone; Neuropsychological Tests; Olanzapine; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology

Disruption in cognition is characteristic of psychiatric illnesses such as schizophrenia. Studies of drugs that improve cognition might provide a better insight into the mechanisms underlying cognitive deficits.. We compared the effects of the antipsychotic drugs aripiprazole, olanzapine, and haloperidol on performance deficit in a test of divided and sustained visual attention, the five-choice serial reaction time task (5-CSRTT), which provides information on attentional functioning (accuracy of visual discrimination), response control (measured by anticipatory and perseverative responses) and speed.. The cognitive deficit was induced by infusion of the competitive NMDA receptor antagonist 3-(R)-2-carboxypiperazin-4-propyl-1-phosphonic acid (CPP) in the rat medial prefrontal cortex (mPFC). In vivo microdialysis was used to compare the effects of aripiprazole, olanzapine and haloperidol on CPP-induced glutamate (GLU) and serotonin (5-HT) release in the mPFC of conscious rats.. Oral aripiprazole (1.0 and 3.0 mg/kg) and olanzapine (0.3 and 1.0 mg/kg), but not haloperidol (0.1 mg/kg), abolished the CPP-induced accuracy deficit and GLU release. Haloperidol and aripiprazole, but not olanzapine, reduced perseverative over-responding, while anticipatory responding was best controlled by olanzapine. However, these effects were not associated with changes in GLU release. No association was found between the effects of these antipsychotics on CPP-induced attentional performance deficits in the 5-CSRTT and 5-HT efflux.. The data confirm that excessive GLU release in the mPFC is associated with attentional deficits. Thus, suppression of GLU release may be a target for the development of novel antipsychotic drugs with greater effect on some aspects of cognitive deficits.

Topics: Analysis of Variance; Animals; Antipsychotic Agents; Aripiprazole; Behavior, Animal; Benzodiazepines; Choice Behavior; Cognition Disorders; Disease Models, Animal; Dose-Response Relationship, Drug; Excitatory Amino Acid Antagonists; Glutamic Acid; Haloperidol; Impulsive Behavior; Male; Microdialysis; Neuropsychological Tests; Olanzapine; Piperazines; Prefrontal Cortex; Quinolones; Rats; Reaction Time; Schizophrenia; Serotonin; Time Factors

This study was conducted to delineate the relationship between self-reported side effects and psychopathology in schizophrenia patients. Patients with schizophrenia completed the Liverpool University Neuroleptic Side Effects Rating Scale for subjective side effects and were evaluated with the Positive and Negative Syndrome Scale for their psychopathology. Based on a series of multiple linear regression analyses, we derived a model accounting for the relationships among the specific domains of psychopathology and red herring (RH) items of the Liverpool University Neuroleptic Side Effects Rating Scale in predicting subjective side effects. The model with anxiety/depressive symptoms and RH serving as mediators between positive symptoms and side effects was found to show good fit. Positive symptoms caused mostly anxiety symptoms and tendency to report RH items, whereby resulting in over-generalized reporting of subjective side effects. However, a large proportion of variance of side effects was explained by RH, which was only partially explained by positive symptoms alone. Therefore, patients with severe levels of positive and anxiety/depressive symptoms may be prone to nocebo-like effects of antipsychotics. Studies that include acute stage patients presenting severe levels of these symptoms should not rely only on the subjective report of side effects but also apply objective measures.

Topics: Adult; Amisulpride; Antipsychotic Agents; Anxiety; Benzodiazepines; Cognition Disorders; Depressive Disorder; Female; Humans; Linear Models; Male; Models, Psychological; Olanzapine; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Sulpiride

Patients' non-compliance in treatments, such as irregular taking of medication, represents an enormous problem with psychiatric patients in general. This difficulty occurs especially in patients suffering from chronic mental illnesses such as schizophrenia. There are not any significant differences in the efficacy of reducing the positive symptoms in schizophrenia between the conventional and the atypical antipsychotics. However, the effects which are manifested in negative schizophrenia symptoms or in the patients' cognitive functioning, favour the atypical antipsychotics. When it comes to adding the subjective well-being of the patients and their improvement of the quality of life, then, the advantages of atypical antipsychotics are unquestionable. New trends in medicine are increasingly impinge on the pharmacoeconomy, which aims at reducing treatment cost. This trend is getting progressively stronger in the world and as such, it certainly will not bypass Croatia. Pharmacists and General Practice doctors (GP) are permitted, by the law, to replace the original medicament prescribed by a specialist doctor, with a cheaper one from the same generic group of medicaments, with a purpose of cutting down the treatment costs. Is there always a valid justification for such practice, and should it become a rule for all the patients out there? This is a case report of a patient who suffers from paranoid schizophrenia. He has been on a treatment with atypical antipsychotics and has kept in a good and stable remission for the past seven years. His therapy consisted of olanzapine in a dose of 15 mg in the evening, throughout the whole period of his 7-year remission. A month ago, his GP doctor self- initially prescribed a generic olanzapine. The impact of this decision on to the mental state of the patient as well as his trust in the treatment itself is described in this report.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Chronic Disease; Cognition Disorders; Cost Savings; Croatia; Drug Costs; Drug Therapy, Combination; Drugs, Generic; Family Practice; Humans; Male; Medication Adherence; Olanzapine; Patient Readmission; Quality of Life; Schizophrenia, Paranoid; Treatment Outcome

We explored the subjective effects associated with olanzapine, risperidone and older antipsychotics.. We conducted a content analysis of an Internet database of comments about prescribed medications.. We analysed 223 comments on risperidone, 170 on olanzapine and 46 relating to three older antipsychotics. The predominant subjective effects produced by all drugs consisted of sedation, cognitive impairment and emotional flattening or indifference. Connections appeared between these effects and Parkinsonian-like symptoms with the older drugs, sexual impairment with risperidone and metabolic effects with olanzapine. The experience of akathisia was frequently linked to suicidal thoughts. Some respondents described how the drugs' subjective effects helped to reduce symptoms of mania, psychosis and anxiety.. The generalisability of Internet data is uncertain. However, the data suggest that adverse subjective effects play a central role in the experience of taking antipsychotic drugs and may be related to the drugs' desired benefits.

Topics: Adult; Affect; Akathisia, Drug-Induced; Antipsychotic Agents; Anxiety Disorders; Attitude to Health; Benzodiazepines; Bipolar Disorder; Cognition Disorders; Female; Health Behavior; Humans; Internet; Male; Middle Aged; Olanzapine; Parkinsonian Disorders; Psychotic Disorders; Risperidone; Sexual Dysfunction, Physiological

This study focuses on exploring the relationship between changes in appetite or eating behaviors and subsequent weight change for adult patients with schizophrenia or bipolar disorder treated with olanzapine and adjunctive potential weight mitigating pharmacotherapy. The aim is not to compare different weight mitigating agents, but to evaluate patients' characteristics and changes in their eating behaviors during treatment. Identification of patient subgroups with different degrees of susceptibility to the effect of weight mitigating agents during olanzapine treatment may aid clinicians in treatment decisions.. Data were obtained from 3 randomized, double-blind, placebo-controlled, 16-week clinical trials. Included were 158 patients with schizophrenia or bipolar disorder and a body mass index (BMI) > or = 25 kg/m2 who had received olanzapine treatment in combination with nizatidine (n = 68), sibutramine (n = 42), or amantadine (n = 48). Individual patients were analyzed for categorical weight loss > or= 2 kg and weight gain > or = 1 kg. Variables that were evaluated as potential predictors of weight outcomes included baseline patient characteristics, factors of the Eating Inventory, individual items of the Eating Behavior Assessment, and the Visual Analog Scale.. Predictors/correlates of weight loss > or = 2 kg included: high baseline BMI, low baseline interest in food, and a decrease from baseline to endpoint in appetite, hunger, or cravings for carbohydrates. Reduced cognitive restraint, increase in hunger, and increased overeating were associated with a higher probability of weight gain > or = 1 kg.. The association between weight gain and lack of cognitive restraint in the presence of increased appetite suggests potential benefit of psychoeducational counseling in conjunction with adjunctive pharmacotherapeutic agents in limiting weight gain during antipsychotic drug therapy.. This analysis was not a clinical trial and did not involve any medical intervention.

Topics: Adult; Amantadine; Appetite; Benzodiazepines; Bipolar Disorder; Cognition Disorders; Cyclobutanes; Drug Therapy, Combination; Feeding Behavior; Female; Humans; Male; Nizatidine; Olanzapine; Randomized Controlled Trials as Topic; Schizophrenia; Weight Gain; Weight Loss

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

The noradrenergic (NE) system mediates cognitive dysfunction in schizophrenia patients, and the NE transporter represents a putative target for cognitive enhancing therapy. In a double-blind placebo-controlled study we evaluated the effect of add-on reboxetine (4 mg/day), a selective norepinephrine reuptake inhibitor (NRI), co-administered with atypical antipsychotic olanzapine (10 mg/day) on cognitive functioning in DSM-IV schizophrenia patients. The Automated Neuropsychological Assessment Metrics battery and Wisconsin Card Sorting Test were used to assess selective cognitive functions at baseline and endpoint (6 weeks). Clinical assessment was also performed. No between-group differences were found in neurocognitive tests, suggesting that reboxetine did not significantly change patients' cognitive performance compared to placebo. Reboxetine was well-tolerated and did not interfere with the therapeutic effect of olanzapine. Long-term studies using higher reboxetine dosages and alternative NRIs (e.g., atomoxetine) are needed to determine the role of NRIs as cognitive enhancers in patients with schizophrenia and other disorders associated with cognitive impairments.

Topics: Adrenergic Uptake Inhibitors; Adult; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Morpholines; Neuropsychological Tests; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Reboxetine; Schizophrenia; Schizophrenic Psychology; Young Adult

Cannabis is the most widely used illicit substance. Delta9-Tetrahydrocannabinol (THC), the major psychoactive component of cannabis, is known to induce cognitive impairment that closely resembles the impairment observed in schizophrenic patients. THC has also been known to impair spatial memory in rats tested in the eight-arm radial maze. We previously reported that microinjection of THC (20 microg/side) into the rat dorsal hippocampus impaired spatial memory and that i.p. injection of THC (6 mg/kg) decreased the extracellular levels of acetylcholine (ACh) in the dorsal hippocampus. In the present study, we compared the effects of olanzapine, an atypical antipsychotic, with those of haloperidol, a typical neuroleptic, on the impairments of spatial memory and decreased ACh levels induced by THC (6 mg/kg, i.p.) in rats. We found that olanzapine (0.1 mg/kg, i.p.) reversed the THC-induced memory deficits and decrease in extracellular ACh levels, whereas haloperidol (0.03-0.3 mg, i.p.) had no effect. These results suggest that olanzapine may improve the THC-induced impairment of spatial memory, partly by enhancing ACh release in the dorsal hippocampus. Therefore, olanzapine could attenuate the acute short-term and working memory deficits induced by cannabis.

Topics: Acetylcholine; Animals; Antipsychotic Agents; Behavior, Animal; Benzodiazepines; Cognition Disorders; Dronabinol; Extracellular Space; Hallucinogens; Haloperidol; Hippocampus; Humans; Male; Marijuana Abuse; Maze Learning; Memory Disorders; Microdialysis; Olanzapine; Rats; Rats, Wistar

Neonatal quinpirole (dopamine D(2)/D(3) agonist) treatment to rats has been shown to increase dopamine D(2) receptor sensitivity throughout the animal's lifetime. Male and female Sprague-Dawley rats were neonatalally treated with quinpirole (1 mg/kg) from postnatal days (P) 1-21 and raised to adulthood. Beginning on P62, rats were administered the atypical antipsychotic olanzapine (2.5 mg/kg) twice daily for 28 days. Starting 1 day after the end of olanzapine treatment, animals were behaviorally tested on the place and match-to-place version of the Morris water maze (MWM) over seven consecutive days, and a yawning behavioral test was also performed to test for sensitivity of the D(2) receptor 1 day following MWM testing. Similar to results from a past study, olanzapine alleviated cognitive impairment on the MWM place version and increases in yawning produced by neonatal quinpirole treatment. Brain tissue analyses showed that neonatal quinpirole treatment resulted in a significant decrease of hipppocampal ChAT and BDNF RNA expression that were unaffected by adulthood olanzapine treatment, although adulthood olanzapine treatment produced a significant increase in cerebellar ChAT RNA expression. There were no significant effects of drug treatment on NGF RNA expression in any brain area. These results show that neonatal quinpirole treatment produced significant decreases of protein RNA expression that is specific to the hippocampus. Although olanzapine alleviated cognitive deficits produced by neonatal quinpirole treatment, it did not affect expression of proteins known to be important in cognitive performance.

Topics: Acetylcholine; Aging; Animals; Animals, Newborn; Antipsychotic Agents; Benzodiazepines; Brain-Derived Neurotrophic Factor; Choline O-Acetyltransferase; Cognition; Cognition Disorders; Dopamine Agonists; Down-Regulation; Female; Hippocampus; Learning Disabilities; Male; Maze Learning; Olanzapine; Quinpirole; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D2; RNA, Messenger; Time

Topics: Aged; Anti-Anxiety Agents; Antipsychotic Agents; Benzodiazepines; Catatonia; Chlorpromazine; Cholinesterase Inhibitors; Cognition Disorders; Creatine Kinase; Dementia; Disease Progression; Donepezil; Female; Humans; Indans; Lorazepam; Muscle Rigidity; Neuroleptic Malignant Syndrome; Olanzapine; Piperidines; Recurrence; Risperidone

Schizophrenia is a neurodevelopmental disorder associated with persistent symptomatology, severe functional disability, and residual morbidity characteristic of neurodegenerative brain diseases. The illness begins with genetic susceptibility and generally expresses itself after puberty through subtle changes that begin during the prodromal stage. Symptoms get progressively worse and tend to become more resistant to treatment with each relapse. Evidence for a neuroprotective effect of some forms of early treatment is beginning to emerge. While the underlying mechanisms remain uncertain, atypical antipsychotics may counteract some of the progressive deteriorative effects by enhancing synaptic plasticity and cellular resilience. However, identifying and treating patients in the earliest disease states presents methodological challenges as there is no consensus on the best methods of intervention and differences in at-risk children are not readily detectable or substantial enough to predict which ones will develop schizophrenia. In this expert roundtable supplement, Jeffrey A. Lieberman, MD, reviews the historical context of progressive deterioration in schizophrenia. Next, Diana O. Perkins, MD, MPH, reviews some of the challenges to early identification of illness as well as the impact of early versus delayed treatment. Finally, L. Fredrik Jarskog, MD, focuses on the neurobiology of functional progression in schizophrenia as well as pharmacology and the potential for neuroprotection.

Topics: Adolescent; Adult; Antipsychotic Agents; Atrophy; Benzodiazepines; Cerebral Cortex; Child; Cognition Disorders; Disease Progression; Haloperidol; Humans; Image Processing, Computer-Assisted; Imaging, Three-Dimensional; Magnetic Resonance Imaging; Neurodegenerative Diseases; Neuroprotective Agents; Neuropsychological Tests; Olanzapine; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Schizotypal Personality Disorder

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

A definition of clinical remission in schizophrenia has recently been proposed. However, it is also known that neuropsychological (NP) impairments may be better predictors of functional outcomes than clinical symptoms. Understanding the relationship between clinical remission and cognitive improvement may be required in order to predict functional improvements, so we examined the development and convergence of clinical remission and neuropsychological improvements in a sample of patients with schizophrenia whose medication was switched to ziprasidone.. One hundred eighty-four patients were switched from their previous treatment with risperidone, olanzapine, or conventional antipsychotics to open-label ziprasidone treatment. One hundred and thirty seven patients were not in remission at baseline and 40 met the clinical criteria for remission at study entry. We rated their symptoms with the PANSS at baseline and after 6 months of treatment. We performed an NP assessment and generated a composite score which was examined for improvements.. Of the 184 cases, 48 (26.1% of the total sample) met the remission criteria at baseline. Of these cases, 41 (85%) sustained their remission at the 6-month follow-up. Of the remaining 136 cases, 33% developed remission by the 6-month follow-up. Thus, a total of 55% of the total sample were in remission at the 6-month endpoint. A comparable number of the patients, 34%, improved by 0.5 SD or more in their cognitive performance. Baseline NP performance was not associated with remission at baseline and did not predict achieving remission over time. Further, clinical remission was not correlated with concurrent NP improvements. However, 33 patients achieved clinical remission and improved by 0.5 SD in their NP performance.. After a switch from previous treatment to open-label ziprasidone more than half of patients with schizophrenia experienced sustained clinical remission over 6 months and 32% of the patients achieving remission experienced a concurrent NP improvement. Later research will be required to determine which aspects of improvement (clinical remission and/or cognitive improvements) are required for functional improvements.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Humans; Middle Aged; Neuropsychological Tests; Olanzapine; Piperazines; Remission Induction; Risperidone; Schizophrenia; Thiazoles

Theory of mind (ToM), the ability to attribute mental states to others, is associated with medial prefrontal cortical (mPFC) activity and is impaired in schizophrenia. Olanzapine or clozapine but not typical antipsychotics or risperidone preferentially affect c-fos expression in mPFC in animals. We tested the hypothesis that schizophrenic patients treated with different antipsychotics would perform differently on ToM tasks. Groups receiving Typicals (n=23), Clozapine (n=18), Olanzapine (n=20) or Risperidone (n=23) and a Control group of healthy volunteers (n=24) were matched for age, gender, handedness and education. ToM functioning was assessed with picture sequence, second-order belief and faux-pas tests. Schizophrenic groups performed similarly to controls on non-ToM conditions. The Olanzapine and Clozapine groups performed similarly to Controls on ToM tasks. The Typicals and Risperidone groups performed worse than the other groups on ToM tasks. We concluded that ToM performance of schizophrenic patients is influenced by the antipsychotic they are taking. Our results suggest that olanzapine or clozapine but not typicals or risperidone may improve or protect ToM ability.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Brief Psychiatric Rating Scale; Clozapine; Cognition; Cognition Disorders; Diagnostic and Statistical Manual of Mental Disorders; Drug Prescriptions; Female; Humans; Male; Neuropsychological Tests; Olanzapine; Risperidone; Schizophrenia; Severity of Illness Index

Impaired ability to detect and correct errors may contribute to poor cognitive and social function in schizophrenia.. To test the hypothesis that impairment in error monitoring contributes to impaired executive function in schizophrenia.. 56 schizophrenia patients and 77 healthy individuals were tested with the Penn Conditional Exclusion test (PCET), a computerised test of executive function which allowed collection of accuracy and latency performance parameters. Error monitoring was assessed by analyzing reaction times for correct (RTC) and incorrect (RTI) responses. Tests of face recognition, working memory (WM) and processing speed were also administered.. Executive error-monitoring effort (EXER), calculated by dividing the difference between RTI and RTC by the sum of RTC and RTI, was significantly smaller in patients than controls. A regression model with the executive function (PCET total errors) as dependent variable showed independent contributions of EXER, verbal WM and spatial WM to test performance and explained 35% of the variance. EXER showed significant association with error-monitoring effort for face recognition in patients but not controls.. Impaired error-monitoring contributes to poor executive function in schizophrenia. Independent contributions of error-monitoring effort and verbal WM to executive functions may reflect distinct contributions of prefrontal and medial frontal cortical dysfunctions. Error-monitoring mechanisms in different cognitive domains may share more neural resources in schizophrenia than in healthy individuals, reflecting inefficient processing.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Chronic Disease; Clozapine; Cognition Disorders; Diagnostic and Statistical Manual of Mental Disorders; Female; Humans; Male; Memory, Short-Term; Neuropsychological Tests; Olanzapine; Piperazines; Reaction Time; Risperidone; Schizophrenia; Self Efficacy; Severity of Illness Index; Thiazoles

We acquired Positron emission tomography with 18-F-deoxyglucose (FDG-PET) and anatomical MRI in 30 never-previously medicated psychotic adolescents (ages 13-20). (FDG-PET) was obtained at baseline and after 8-9 weeks of a randomized double-blind trial of either olanzapine or haloperidol. Neuropsychological tests of executive function were also obtained. Patients carried out the serial verbal learning task, a modification of the California Verbal Learning Test, during the uptake of the FDG. PET scans were coregistered with spoiled gradient MRI (TR=24, TE=5, flip angle 40 degrees, slice thickness 1.2 mm, field of view 230 mm) for accurate anatomical identification of regions of interest traced on the MRI. Twenty-two of the thirty patients completed the second PET and clinical evaluation. Individuals treated with olanzapine increased relative metabolic rates in the frontal lobe more than the occipital lobe while patients treated with haloperidol failed to increase frontal metabolic rates and did not show an anteroposterior gradient in medication response. Haloperidol increased striatal metabolic rate more than olanzapine. Both drugs increased thalamic metabolic rates and this increase was significantly larger in younger (age 13-15) than older (16-21) patients.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Brain; Cognition Disorders; Female; Fluorodeoxyglucose F18; Frontal Lobe; Haloperidol; Humans; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Occipital Lobe; Olanzapine; Positron-Emission Tomography; Psychotic Disorders; Radiopharmaceuticals; Temporal Lobe

This study examined the short-term effects of first- and second-generation antipsychotic medications on social cognition and basic cognition.. One hundred patients with schizophrenia or schizoaffective disorder participated in an 8 week, double-blind study of risperidone, olanzapine, and haloperidol. Participants were administered multiple measures of social cognition, basic cognition, and clinical symptoms at baseline, the end of week 4, and the end of week 8. Seventy-three patients completed the baseline assessment and at least one other assessment. Data were analyzed with mixed-effects analyses of covariance. For data reduction, the social cognitive measures were clustered into a summary score, and the cognitive measures were clustered into two summary scores: general cognitive ability and processing speed.. There were no treatment-related differences on any of the three summary scores. Social cognition did not show within-group changes over time either by itself or after control for the cognitive clusters. One cognitive score (general cognitive ability) increased during the study period for all three medication groups.. The present study included a rather thorough assessment of social cognition and did not find any evidence of between-group or within-group effects of antipsychotic medication on social cognition.

Topics: Ambulatory Care; Antipsychotic Agents; Benzodiazepines; Cognition; Cognition Disorders; Emotions; Facial Expression; Female; Haloperidol; Humans; Male; Middle Aged; Neuropsychological Tests; Olanzapine; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology; Social Perception; Treatment Outcome

We report a case of recurrent psychosis, spanning decades, with full inter-episode recovery and minimal functional impairment. While it is difficult to classify this disorder using DSM IV-TR criteria, Leonhard and others have described a 'cycloid psychosis' that correlates well with the phenomenology and course of this case. We believe this may represent a subset within the ICD-10 category of 'acute and transient psychotic disorders'. While this disorder, of unknown incidence, is not well reported in the U.S., it is worthy of further investigation and clinical attention given its generally favorable prognosis and potentially distinct pathophysiology and treatment.

Topics: Acute Disease; Aged; Benzodiazepines; Cognition Disorders; Delusions; Diagnosis, Differential; Diagnostic and Statistical Manual of Mental Disorders; Drug Therapy, Combination; Hallucinations; Hospitalization; Humans; Lorazepam; Male; Olanzapine; Psychomotor Agitation; Psychotic Disorders; Recurrence

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

The case presented highlights the difficult differential diagnosis of memory-sparing cognitive decline in an elderly patient with previously stable bipolar illness. Many disorders can contribute to cognitive and behavioral deterioration in this population, including reversible causes, particularly delirium and psychiatric illness, and irreversible structural or progressive processes including vascular disease, dementia with Lewy bodies, normal-pressure hydrocephalus, and frontotemporal dementia.

Topics: Age of Onset; Aged; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Brain; Cognition Disorders; Dementia; Dementia, Vascular; Disease Progression; Humans; Lithium Compounds; Male; Memory; Mental Disorders; Neuropharmacology; Olanzapine; Psychoses, Substance-Induced; Recovery of Function

Cognitive dysfunction is increasingly considered to be the strongest clinical predictor of poor long-term outcome in schizophrenia. Associations have been found between the severity of cognitive deficits and social dysfunction, impairments in independent living, occupational limitations, and disturbances in quality of life (QOL).. In this cross-sectional study, the relationships of cognitive deficits and treatment outcomes in terms of QOL, needs, and psychosocial functioning were examined in 60 outpatients with schizophrenia who had a duration of illness over 2 years and had been treated with either clozapine or olanzapine for at least 6 months.. The present study suggests that cognitive functioning might be a predictor of work functioning/independent living outcome in stabilized patients with schizophrenia: deficits of visual memory and working memory were negatively associated with occupational functioning, and older patients lived independently and/or in a stable partnership more often. The patients' assessments of QOL and needs for care did not show any significant associations with cognitive functioning.. These findings suggest that cognitive functioning is a key determinant of work functioning/independent living for stable outpatients with schizophrenia.

Topics: Adult; Age Factors; Antipsychotic Agents; Benzodiazepines; Clozapine; Cognition; Cognition Disorders; Comorbidity; Cross-Sectional Studies; Female; Humans; Male; Memory Disorders; Neuropsychological Tests; Olanzapine; Outpatients; Predictive Value of Tests; Quality of Life; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Recently we reported the pharmacological characterization of the 9,10-dihydropyrrolo[1,3]benzothiazepine derivative (S)-(+)-8 as a novel atypical antipsychotic agent. This compound had an optimum pK(i) 5-HT(2A)/D(2) ratio of 1.21 (pK(i) 5-HT(2A) = 8.83; pK(i) D(2) = 7.79). The lower D(2) receptor affinity of (S)-(+)-8 compared to its enantiomer was explained by the difficulty in reaching the conformation required to optimally fulfill the D(2) pharmacophore. With the aim of finding novel atypical antipsychotics we further investigated the core structure of (S)-(+)-8, synthesizing analogues with specific substituents; the structure-activity relationship (SAR) study was also expanded with the design and synthesis of other analogues characterized by a pyrrolo[2,1-b][1,3]benzothiazepine skeleton, substituted on the benzo-fused ring or on the pyrrole system. On the 9,10-dihydro analogues the substituents introduced on the pyrrole ring were detrimental to affinity for dopamine and for 5-HT(2A) receptors, but the introduction of a double bond at C-9/10 on the structure of (S)-(+)-8 led to a potent D(2)/5-HT(2A) receptor ligand with a typical binding profile (9f, pK(i) 5-HT(2A)/D(2) ratio of 1.01, log Y = 8.43). Then, to reduce D(2) receptor affinity and restore atypicality on unsaturated analogues, we exploited the effect of specific substitutions on the tricyclic system of 9f. Through a molecular modeling approach we generated a novel series of potential atypical antipsychotic agents, with optimized 5HT(2A)/D(2) receptor affinity ratios and that were easier to synthesize and purify than the reference compound (S)-(+)-8. A number of SAR trends were identified, and among the analogues synthesized and tested in binding assays, 9d and 9m were identified as the most interesting, giving atypical log Y scores respectively 4.98 and 3.18 (pK(i) 5-HT(2A)/D(2) ratios of 1.20 and 1.30, respectively). They had a multireceptor affinity profile and could be promising atypical agents. Compound 9d, whose synthesis is easier and whose binding profile is atypical (log Y score similar to that of olanzapine, 3.89), was selected for further biological investigation. Pharmacological and biochemical studies confirmed an atypical antipsychotic profile in vivo. The compound was active on conditioned avoidance response at 1.1 mg/kg, a dose 100-times lower than that required to cause catalepsy (ED(50) >90 mg/kg), it induced a negligible increase of prolactin serum levels after single and m

Topics: Animals; Antipsychotic Agents; Avoidance Learning; Benzothiepins; Catalepsy; Cognition Disorders; Dopamine Antagonists; Humans; Male; Mice; Models, Molecular; Motor Activity; Pituitary Gland, Anterior; Prolactin; Pyrroles; Rats; Rats, Inbred F344; Rats, Wistar; Receptors, Dopamine D1; Receptors, Dopamine D2; Receptors, Dopamine D3; Receptors, Serotonin, 5-HT2; Serotonin Antagonists; Structure-Activity Relationship; Thiazepines

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

The exponential growth in the prevalence of cognitive impairment of old patients leads the physicians to deal with a larger incidence of behavioral disorders (such as excitement,aggressiveness), and psychotic symptoms (such as delirium and visual hallucinations). The presence of psychotic troubles in dementia causes a remarkable distress to caregivers and involves higher difficulties in the patient management. The estimates of such troubles range between 15 and 75 %. Geriatric assessment and the management of behavioral troubles require a prompt evaluation of all their possible causes. As a matter of fact, their appearance often reveals a physical disturbance (pain, fever, etc.), or adverse environmental conditions, or it could also be a consequence of a multiple drug therapy. For this reason,the use of antipsychotics should always be preceded by an accurate clinical diagnosis.Anxiolytic, anti-depressive, anti-convulsive and anti-psychotic drugs are among the therapeutic strategies for the management of the psychogeriatric patient. Atypical antipsychotics seem to be able to decrease the psychotic symptoms, with low levels of therapeutic failure. They also reduce extrapyramidal effects and the growth of prolactine hormone, which is quite useful when dealing with very old patients. Risperidone and olanzapine are two atypical anti-psychotics, which already proved to be adequate and well tolerated during the treatment of schizophrenia and of acute maniacal disorders. Our experience, with a population of patients followed by our Alzheimer Evaluation Unit (AEU), confirms that a low dose of olanzapine (5mg/day) and risperidone (0.5-1.0 mg/day) are effective in lowering behavioral disturbances, and psychotic symptoms due to dementia. Even in the long run,low doses of these drugs are still well tolerated. Higher levels of risperidone (> 1 mg/die)often caused extra-pyramidal symptoms such as rigidity and dyskinesia, whereas higher levels of olanzapine (> 5 mg/day) lead to an exceeding sedation. The management of behavioral disturbances is one of the most important goals in the global treatment of patients affected by dementia, to the extent of improving the quality of life. Atypical antipsychotics are preferable compared to old-generation drugs, therefore, they are the key therapeutic strategy we cannot renounce.

Topics: Activities of Daily Living; Aged; Aged, 80 and over; Aggression; Alzheimer Disease; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Cognition Disorders; Female; Humans; Male; Mental Disorders; Middle Aged; Olanzapine; Psychotic Disorders; Risperidone

Topics: Acute Disease; Adolescent; Antipsychotic Agents; Benzodiazepines; Brain; Cognition Disorders; Electroencephalography; Humans; Lamotrigine; Male; Neuropsychological Tests; Olanzapine; Recovery of Function; Schizophrenia; Severity of Illness Index; Triazines

Topics: Aged; Aged, 80 and over; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Carbamazepine; Cognition Disorders; Hallucinations; Humans; Male; Music; Olanzapine; Syndrome; Visual Fields

The aim of this study was to evaluate the effects of atypical antipsychotics on cognitive function in schizophrenic patients under clinical routine conditions.. Schizophrenic patients (n = 78) were evaluated on neuropsychological tests of attention, short-term- and working memory, learning, long-term memory (retention) and executive function. Data were analyzed according to medication, severity of illness and age.. We observed that treatment with atypical antipsychotics compared to conventional neuroleptics was significantly associated with a more favorable effect on cognitive function. Especially in short-term memory and retention a clear advantage of atypical antipsychotics could be seen.. Results from this study suggest that even under clinical routine conditions atypical antipsychotics have an advantage on cognitive function when compared with conventional neuroleptics.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Cognition Disorders; Drug Therapy, Combination; Female; Haloperidol; Humans; Male; Middle Aged; Neuropsychological Tests; Olanzapine; Pirenzepine; Product Surveillance, Postmarketing; Risperidone; Schizophrenia; Schizophrenic Psychology

Traumatic brain injury can cause a variety of impairments, including persistent alterations in personality, mood, and cognition. Antipsychotic agents are frequently used to treat pathologic behaviors in traumatic brain injury patients, but the influence of prolonged administration of such drugs on cognition after injury is unknown. The effects of two antipsychotic drugs on cognitive recovery after traumatic brain injury were assessed using the fluid percussion model in rats.. The typical antipsychotic, haloperidol, and the third-generation antipsychotic, olanzapine, were administered via intraperitoneal injection beginning 24 hr after injury and continuing daily for the duration of the study. Morris water maze performance was assessed on days 11-15 postinjury.. Haloperidol, an antagonist acting on D2-like dopamine receptors, exacerbated the cognitive deficits induced by injury, as injured rats treated with 0.30 mg/kg haloperidol performed worse in the Morris water maze than injured rats treated with vehicle.. Our results demonstrate the importance of the D2 receptor in cognitive recovery after traumatic brain injury. Also, the data illustrate that some classes of antipsychotic drugs may influence cognitive recovery, and further research is needed to determine the optimal pharmacologic treatment of aggression, agitation, and other pathologic behaviors in patients with traumatic brain injury.

Topics: Analysis of Variance; Animals; Antipsychotic Agents; Benzodiazepines; Brain Injuries; Cognition Disorders; Dopamine Antagonists; Dose-Response Relationship, Drug; Haloperidol; Injections, Intraperitoneal; Male; Maze Learning; Olanzapine; Pirenzepine; Rats; Rats, Sprague-Dawley; Swimming

Topics: Adult; Benzodiazepines; Brain; Capgras Syndrome; Cognition Disorders; Depersonalization; Female; Humans; Magnetic Resonance Imaging; Olanzapine; Pirenzepine; Selective Serotonin Reuptake Inhibitors; Self Concept; Severity of Illness Index; Single Parent; Syndrome; Wechsler Scales

Topics: Benzodiazepines; Cognition Disorders; Dopamine Antagonists; Haloperidol; Humans; Olanzapine; Pirenzepine; Risperidone; Schizophrenia; Selective Serotonin Reuptake Inhibitors

The primary aim of our study is to evaluate the level of insight during the switch from a classical antipsychotic drug to a atypical neuroleptic. Twenty-two schizophrenic patients were admitted to the study, 9 were male and 13 were female. Standardized questionnaire were: Scale for Assessment of Negative Symptoms (SANS), Scale for Assessment of Positive Symptoms (SAPS), Brief Psychiatric Rating Scale (BPRS) and Schedule for Assessing the three components of Insight (SAI). All patients were receiving haloperidol at time of recruitment. Eight patients were switched to clozapine, 3 to risperidone and 11 to olanzapine. The global function, measured with BPRS, increased after administration of atypical antipsychotics. The positive and negative symptoms were reduced. The level of insight was increased after the administration of the atypical antipsychotics. The cognitive effect of the atypical antipsychotics changed the level of insight and augmented the compliance.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Cognition; Cognition Disorders; Female; Haloperidol; Humans; Male; Olanzapine; Patient Compliance; Pirenzepine; Risperidone; Schizophrenia; Severity of Illness Index; Treatment Outcome

Topics: Antipsychotic Agents; Benzodiazepines; Cognition; Cognition Disorders; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Olanzapine; Pirenzepine; Randomized Controlled Trials as Topic; Research Design; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Patients with schizophrenia have deficits in attention, cognition, and information processing. Measures such as P50 suppression are used to study cognitive and attentional dysfunction among these patients. P50 suppression is an operational measure of sensory gating that can be assessed by averaging electroencephalographic responses to multiple pairs of auditory clicks separated by 500 msec. Normally, the P50 response to the second click is smaller than the response to the first click. Many studies have demonstrated that schizophrenia patients have deficient P50 suppression, meaning that the difference between the first and second clicks is not as large as normal. Atypical antipsychotic medications may have superior clinical efficacy for negative symptoms and cognitive deficits. It is important, therefore, to evaluate the effects of atypical antipsychotic medications on measures such as P50 suppression.. P50 suppression of 13 patients with schizophrenia receiving clinically effective doses of clozapine, olanzapine, or risperidone (classified as atypical antipsychotic medications) was compared to that of 13 patients receiving conventional antipsychotic medications.. The patient groups did not differ on clinical or demographic measures. The patients receiving atypical antipsychotic medications had normal-range P50 suppression (mean=72%). In contrast, the patients receiving typical antipsychotic medications had dramatically lower P50 suppression (mean=27%).. The results support the hypothesis that patients treated with atypical antipsychotic medications have normal P50 measures of sensory gating. Longitudinal within-subjects studies are warranted to clarify the mechanisms mediating this effect.

Topics: Acoustic Stimulation; Adult; Antipsychotic Agents; Auditory Perception; Benzodiazepines; Clozapine; Cognition Disorders; Electroencephalography; Evoked Potentials, Auditory; Female; Humans; Male; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Risperidone; Schizophrenia; Schizophrenic Psychology

Dementia with Lewy bodies (DLB) is now a well-recognized form of dementia in which psychosis and behavioural disturbance are common. Treatment with conventional neuroleptics is often very poorly tolerated. Olanzapine, a newly introduced atypical neuroleptic which binds to multiple receptor types with relatively low affinity for D2 receptors, may be a useful treatment option in DLB.. The Behavioural Pathology in Alzheimer's Disease Rating Scale, The Neuropsychiatric Inventory, Unified Parkinson's Disease Rating Scale and The Webster Disability Scale.. We present the results of eight DLB patients with associated psychotic and behavioural difficulties. All patients were given olanzapine 2.5-7.5 mg. Their psychotic phenomena and behavioural and extrapyramidal symptoms were monitored at 2-weekly intervals.. Three out of the eight patients could not tolerate olanzapine even at the lowest available dose. Two patients had clear improvement in psychotic and behavioural symptoms. Three patients were able to tolerate olanzapine but gained only minimal benefit.. Olanzapine at the doses used conferred little advantage over conventional neuroleptics and should only be given with great caution to patients with DLB. The utility of smaller doses deserves further evaluation.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Contraindications; Delusions; Dementia; Depression; Dose-Response Relationship, Drug; Female; Hallucinations; Humans; Lewy Bodies; Male; Olanzapine; Parkinson Disease; Pirenzepine; Treatment Outcome