A prospective,open-label trial of olanzapine in adolescents with schizophrenia

BACKGROUND: Olanzapine is an atypical antipsychotic that has efficacy in adults with psychotic disorders. This preliminary study examined the effectiveness of olanzapine in adolescents with schizophrenia or its related conditions. METHOD: Adolescents aged 12-17 years (inclusive) with a diagnosis of schizophrenia, schizoaffective, or schizophreniform disorder were enrolled in this 8-week, open-label, outpatient study. The Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions Scale (CGI), and the Children's Global Assessment Scale (CGAS) were administered as outcome measures. Extrapyramidal side effects were assessed at each visit. Olanzapine was initiated at a dose of 2.5 mg/day and could be increased to a maximum total daily dose of 20 mg. RESULTS: Sixteen participants with a mean age of 13.8 (SD = 1.5) years were treated. Significant improvements were found in the PANSS, CGI severity, and CGAS scores. Reductions in both positive and negative symptoms were found. Increased appetite and sedation were the most frequently reported side effects. Two subjects required treatment for extrapyramidal side effects. CONCLUSIONS: Psychotic symptoms significantly improved during study. Overall, olanzapine was well tolerated. Future studies are needed to confirm these findings, to assess long-term treatment outcomes, and to compare the effectiveness of olanzapine with that of other antipsychotics.     

Effectiveness, safety, and tolerability of risperidone in adolescents with schizophrenia: an open-label study

Data on risperidone's efficacy and tolerability in adolescents with schizophrenia are scarce. We found only one prospective, open-label study in this population. The aim of this open-label, prospective study was to estimate the effectiveness, safety, and tolerability of risperidone treatment in adolescents with first-episode schizophrenia. Subjects were adolescent inpatients diagnosed with Diagnostic and Statistical Manual of Mental Disorders (fourth edition) first-episode schizophrenia by the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present Episode version. Most of the patients (10/11) were drug na?ve. Improvement was assessed during the first 6 weeks of treatment using the Positive and Negative Syndrome Scale (PANSS), the Brief Psychiatric Rating Scale (BPRS), and the Clinical Global Impression (CGI) scale. Side effects were monitored using the Abnormal Involuntary Movement Scale, the Simpson-Angus Scale, the Barnes Akathisia Rating Scale, and the Udvalg for Kliniske Undersogelser Side Effect Rating Scale. Eleven adolescents between 15.5 and 20 years of age (mean = 17.27, SD = 1.27 years) were included in this study. Risperidone in an average dose of 3.14 mg/day (SD = 1.60 mg/day) produced a significant improvement on the total PANSS score (28%, p < 0.01), BPRS score (30.11%, p < 0.01), and CGI-Severity score (31.36%, p < 0.01). Risperidone was ineffective in the treatment of negative signs as assessed by the PANSS. The major side effects were extrapyramidal side effects, somnolence, depression, and weight gain. In conclusion risperidone appears to be a safe, acceptably tolerated, and effective antipsychotic medication for the treatment of adolescent-onset schizophrenia.     

An open-label study of olanzapine in children and adolescents with schizophrenia

The purpose of this open-label study was to evaluate the use of olanzapine in the treatment of children and adolescents with schizophrenia. Sixteen children who were 8-17 years of age and met DSM-IV criteria for schizophrenia were admitted into a 10-week, open-label, optimizing dose study of olanzapine. The Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS), and the Clinical Global Impression (CGI)-Severity/Improvement scales were used to assess improvement during the study. Of the 16 subjects who completed the study, 12 demonstrated significant improvement on end of treatment BPRS, CGI, and PANSS scores compared with baseline. Male subjects showed greater improvement and also gained more weight. Weight gain occurred in all but 2 subjects. Weight gain was significant, with patients averaging a gain of about 6.2 kg during the 6-week course of the study. Two of the subjects experienced extrapyramidal symptoms. The average dose of olanzapine for all subjects was 0.17 mg/kg.     

Pharmacokinetics, tolerability, and clinical effectiveness of quetiapine fumarate: an open-label trial in adolescents with psychotic disorders

BACKGROUND: This is the first investigation of the pharmacokinetics, tolerability, and efficacy of quetiapine fumarate in adolescents with chronic or intermittent psychotic disorders. METHOD: Ten patients with DSM-IV chronic or intermittent psychotic disorders (ages 12.3 through 15.9 years) participated in an open-label, rising-dose trial and received oral doses of quetiapine twice daily (b.i.d.), starting at 25 mg b.i.d. and reaching 400 mg b.i.d. by day 20. The trial ended on day 23. Key assessments were pharmacokinetic analysis of plasma quetiapine concentrations and neurologic, safety, and efficacy evaluations. RESULTS: No statistically significant differences were observed between 100-mg b.i.d. and 400-mg b.i.d. quetiapine regimens for total body clearance, dose-normalized area under the plasma concentration-time curve, or dose-normalized premorning- or postmorning-dose trough plasma values obtained under steady-state conditions after multiple-dose regimens. No unexpected side effects occurred with quetiapine therapy, and no statistically significant changes from baseline were observed for the UKU Side Effect Rating Scale items that were rated. No serious adverse events or clinically important changes in hematology or clinical chemistry variables were reported. The most common adverse events were postural tachycardia and insomnia. Extrapyramidal side effects improved, as evidenced by significant (p < .05) decreases from baseline to endpoint in the mean Simpson-Angus Scale total scores and Barnes Akathisia Scale scores. Quetiapine improved positive and negative symptoms, as shown by significant (p < .05) decreases from baseline to endpoint in the mean Brief Psychiatric Rating Scale total score, the Clinical Global Impressions-Severity of Illness scale, and the Modified Scale for the Assessment of Negative Symptoms summary score. CONCLUSION: Quetiapine pharmacokinetics were dose proportional in adolescents and were similar to those previously reported for adults. Quetiapine was well tolerated and effective in the small number of adolescents studied.     

Effectiveness and tolerability of citalopram for the treatment of depression and anxiety disorders in children and adolescents: an open-label study

To assess the effectiveness and tolerability of citalopram for the acute treatment of children and adolescents suffering from depression and/or anxiety disorders. As much as 78 outpatients, aged 7–18 years with a diagnosis of depressive and/or anxiety disorder, completed an 8-week open trial with citalopram (20–40 mg/day). Outcome, side effects and suicidality were assessed weekly to bi-weekly using appropriate rating scales. At endpoint 56% of subjects were found to be responders (Clinical Global Impression-Improvement [CGI-I] Scale ≤ 2). Subjects with less severe psychopathology and subjects with anxiety disorders showed a more favorable response. As much as 43% of depressed and 51% of anxious subjects had a 50% or greater reduction in scores on our secondary outcome measures, Children’s Depression Rating Scale-Revised (CDRS-R) and Screen for Child Anxiety Related Emotional Disorders (SCARED). Most reported adverse events were mild to moderate and did not affect medication adherence. No increase in suicidality was observed during the study. Citalopram was moderately effective, generally well tolerated and safe for the acute treatment of depressed and anxious children and adolescents.     

Low-dose fluvoxamine treatment of children and adolescents with pervasive developmental disorders: a prospective,open-label study

The objective of this study was to assess the efficacy and tolerability of low-dose fluvoxamine (1.5 mg/kg/day) in youngsters with pervasive developmental disorders (PDDs). This was a prospective, open-label trial that included 18 subjects with a mean age of 11.3 ± 3.6 years. Fourteen children (78%) completed the 10-week study. Premature discontinuation due to behavioral activation occurred in three participants. Although there was no response for the group as a whole, eight subjects (including all four females) were considered at least partial responders in intent-to-treat analyses. Neither pubertal status nor serotonin levels predicted clinical response. Fluvoxamine can be beneficial in the treatment of select children and adolescents with PDDs. Gender differences in selective serotonin reuptake inhibitor (SSRI) response warrant further investigation.     

Obsessive-compulsive symptoms during treatment with olanzapine and risperidone: a prospective study of 113 patients with recent-onset schizophrenia or related disorders

OBJECTIVE: To determine whether severity of obsessive-compulsive symptoms (OCS) differs during treatment with olanzapine or risperidone and to establish whether duration of antipsychotic treatment is related to severity of OCS. METHOD: We conducted a prospective study of consecutively hospitalized young patients (mean age = 22.4 years) with DSM-IV schizophrenia or related disorders (N = 113) who were treated with olanzapine or risperidone. Olanzapine or risperidone was randomly prescribed for patients who were drug-naive or were treated with typical antipsychotics before admission (N = 36). Patients who had started olanzapine (N = 39) or risperidone treatment (N = 23) prior to admission continued with that medication if they showed initial clinical response. Patients who prior to admission started olanzapine (N = 6) or risperidone (N = 9) but showed no response or suffered from adverse effects switched at admission to risperidone or olanzapine, respectively. Medical records, parents, and patients revealed information on duration of treatment and compliance with olanzapine or risperidone prior to admission. The Yale-Brown Obsessive Compulsive Scale (YBOCS) was administered at admission and 6 weeks thereafter. RESULTS: At baseline and 6-week assessments, OCS were found in about 30% of 106 evaluable cases and 15% met DSM-IV criteria for obsessive-compulsive disorder. No differences in OCS were found in the patients randomly assigned to olanzapine or risperidone. The 35 subjects treated with olanzapine at both assessments had significantly (p = .01) more severe OCS at week 6 than the 20 subjects treated with risperidone at both assessments. Duration of treatment with olanzapine was significantly (p < .01) related to severity of OCS. CONCLUSION: There are no differences in the short-term propensity of olanzapine or risperidone to induce or exacerbate OCS. However, severity of OCS was associated with duration of treatment with olanzapine.     

Effectiveness and tolerability of schizophrenia treatment in Central and Eastern Europe: results after 1 year from a prospective,observational study (IC-SOHO)

Objective. The Intercontinental Schizophrenia Outpatient Health Outcomes (IC-SOHO) study is intended to complement smaller, shorter-term observational studies and randomised controlled clinical trials in providing information on the treatment of schizophrenia in various geographies that have not been well studied previously.

Methods. Interim results after 12 months are presented for a subset of patients from eight Central and Eastern European (CEE) countries initiating or switching to olanzapine, risperidone, or typical antipsychotic monotherapy at Baseline (n=1387).

Results. Patients initially prescribed olanzapine and risperidone experienced significantly greater improvements in a broad range of schizophrenia symptom domains compared with patients prescribed typicals. Furthermore, patients in the olanzapine group showed significantly greater improvements in overall and negative symptom domains compared with the risperidone group (all P≤0.05). While patients in the olanzapine group gained more weight than the other two groups, they had significantly lower odds of developing extrapyramidal symptoms, loss of libido, and sexual dysfunction. Patients initially prescribed olanzapine were also significantly less likely to have changed or added antipsychotics during 12 months of treatment compared with the risperidone and typicals groups.

Conclusion. In this CEE sample, schizophrenia treatment outcomes after 12 months varied between patients initially prescribed different antipsychotics.     

Amoxapine shows atypical antipsychotic effects in patients with schizophrenia: results from a prospective open-label study

OBJECTIVE: Amoxapine is marketed as an antidepressant. However, its receptor occupancy, in vitro and in vivo, and its effects in pre-clinical models are very similar to atypical antipsychotics. To examine if this leads to an atypical antipsychotic effect in the clinical context, the authors examined the antipsychotic and side-effect profile of amoxapine in acutely psychotic patients with schizophrenia. METHODS: Seventeen patients were enrolled and 15 completed a prospective open-label 6-week study of amoxapine starting with a fixed-starting dose (150 mg/h) with standardized titration up to 250 mg/h, if required. Positive, negative, affective symptoms and side-effects were monitored using standardized weekly assessments. RESULTS: Amoxapine (median final dose 210 mg/h) was well-tolerated and showed significant improvement in positive and negative symptoms (both p<0.001), with a trend towards improvement in mood symptoms and no treatment-emergent extrapyramidal side-effects, akathisia or weight gain. Prolactin elevation was observed. CONCLUSION: These clinical data lend support to the pre-clinical suggestions that amoxapine may be an atypical antipsychotic. Given its lack of weight gain and that it is considerably less expensive than current options, amoxapine could be a valuable alternative for some patients. These considerations strongly call for more systematic, double-blind studies of amoxapine as an atypical antipsychotic.     

Olanzapine in the treatment of depression with psychotic features: A prospective open-label study

Objective. Depression with psychotic features is a severe subtype of major depression associated with the presence of delusions, hallucinations and specific neurobiological features. Despite clinical consensus and guideline recommendations, data comparing the efficacy of combining antipsychotics with antidepressants compared to antidepressants alone remain inconclusive. The aim of the study was to investigate effectiveness and tolerability of the atypical antipsychotic olanzapine in acute depression with psychotic features. Methods. Seventeen inpatients with major depressive disorder with psychosis (MDDp) were treated with a combination of an antidepressant and olanzapine for 6 weeks in a prospective open-label study. Depressive and psychotic symptoms, extrapyramidal and general side effects were assessed every 2 weeks. Sixteen patients were eligible for final analysis. Results. The Brief Psychiatric Rating Scale (BPRS) showed a 30% symptom reduction after week 2, a 45% symptom reduction after week 4 and no considerable improvement thereafter. Depressive symptoms (Bech–Rafaelsen Melancholia Scale, BRMS) receded by 37% after week 2 and 50% after week 4. No extrapyramidal side effects occurred. Conclusion. Olanzapine is effective and tolerable in combination with an antidepressant in an MDDp inpatient sample. The results concur with data supporting good efficacy in negative and depressive symptoms of patients with schizophrenic and schizoaffective diseases.     

A prospective open-label treatment trial of olanzapine monotherapy in children and adolescents with bipolar disorder

OBJECTIVE: The goal of this study was to assess the effectiveness and tolerability of olanzapine in the treatment of acute mania in children and adolescents. METHODS: This was an 8-week, open-label, prospective study of olanzapine monotherapy (dose range 2.5-20 mg/day) involving 23 bipolar youths (manic, mixed, or hypomanic; 5-14 years old). Weekly assessments were made using the Young Mania Rating Scale (YMRS), Clinical Global Impressions Severity Scale (CGI-S), Brief Psychiatric Rating Scale, and Children's Depression Rating Scale. Adverse events were assessed through self-reports, vital sign and weight monitoring, laboratory analytes, and extrapyramidal symptom rating scales (Barnes Akathisia Scale, Simpson-Angus Scale, and Abnormal Involuntary Movement Scale). RESULTS: Twenty-two of the 23 youths (96%) completed the study. Olanzapine treatment was associated with significant improvement in mean YMRS score (-19.0 +/- 9.2, p < 0.001). Using predefined criteria for improvement of > or = 30% decline in the YMRS and a CGI-S Mania score of < or = 3 at endpoint, the overall response rate was 61%. Overall, olanzapine was well tolerated, and extrapyramidal symptom measures were not significantly different from baseline. Body weight increased significantly over the study (5.0 +/- 2.3 kg, p < 0.001). CONCLUSIONS: Open-label olanzapine treatment was efficacious and well tolerated in the treatment of acute mania in youths with bipolar disorder. Future placebo-controlled, double-blind studies are warranted.     

Effectiveness of antipsychotic maintenance therapy with quetiapine in comparison with risperidone and olanzapine in routine schizophrenia treatment: results of a prospective observational trial

Objective of this observational trial is to examine the effects of quetiapine in comparison with olanzapine and risperidone on clinical outcomes and quality of life in patients with schizophrenia and schizoaffective disorder in routine care. 374 adult persons with schizophrenia or schizoaffective disorder prescribed antipsychotic maintenance therapy with quetiapine, olanzapine, or risperidone at discharge from inpatient treatment were included. Clinical and psychosocial outcomes were assessed before discharge and at 6, 12, 18, and 24?months. Statistical analyses were conducted by mixed-effects regression models for longitudinal data. The propensity score method was used to control for selection bias. Patients discharged on olanzapine had significantly lower hospital readmissions than those receiving quetiapine or risperidone. The average chlorpromazine equivalent dose of quetiapine was higher than in patients treated with olanzapine or risperidone. No further significant differences between treatment groups were found. Quetiapine and risperidone are less effective in preventing the need for psychiatric inpatient care than olanzapine, and higher chlorpromazine equivalent doses of quetiapine are needed to obtain clinical effects similar to those of olanzapine and risperidone.     

Resource utilization in a Canadian national study of people with schizophrenia and related psychotic disorders

OBJECTIVE: To determine how the use of the newer, so called atypical antipsychotic medications, effects the pharmacoeconomic treatment burden of schizophrenia and related conditions and to provide a clear comparison of the costs and risks associated with these atypical drugs. METHOD: In this 2-year, open-label, prospective study, resource utilization (RU) data were collected on 160 patients with these conditions. A comparison between risks and costs was performed by combining the generalized CNOMSS data on both economic factors and risk assessments. RESULTS: The main findings of the study were that the total adjusted 1- and 2-year costs were lowest for quetiapine. Drug acquisition costs were lowest for risperidone for both the 1- and 2-year cohorts. Clozapine use was predictably associated with the highest overall and medication costs at both 1 and 2 years. CONCLUSION: Treatment with risperidone or quetiapine was associated with the lowest overall costs when compared with olanzapine or clozapine.     

奥氮平治疗精神分裂症临床观察

目的：探讨奥氮平治疗精神分裂症的疗效与安全性。方法：对123例精神分裂症患者随机分成两组,奥氮平组61例,氯氮平组62例,于治疗前和治疗1、2、4、6、8周末进行阳性与阴性症状量表（PANSS）及副反应量表（TESS）评定疗效及不良反应。结果：奥氮平与氯氮平总的疗效差异无显著性;在认知因子和阴性症状方面,以奥氮平显著较好。奥氮平主要不良反应明显低于氯氮平。结论：奥氮平是一种安全、有效的非典型抗精神病药。     

Risperidone in the treatment of delirium: results from a prospective open-label trial

BACKGROUND: Effective treatment is necessary to reverse delirium and prevent potentially serious consequences. METHOD: Patients were identified for screening by initial chart review of all consecutive admissions to the general medical or surgical wards at the Department of Veterans Affairs hospital and the University of Mississippi Medical Center in Jackson, Mississippi, between November 2000 and April 2002. Medically ill patients with delirium defined by DSM-IV criteria and a Delirium Rating Scale (DRS) score of >or= 13 were given risperidone, 0.5 mg, twice daily, with additional doses permitted on day 1 for target symptoms. Total day 1 dosage was given daily until the DRS score was 相似文献