Rehospitalization rates of chronically ill schizophrenic patients discharged on a regimen of risperidone, olanzapine, or conventional antipsychotics

OBJECTIVE: The purpose of this study was to compare the rehospitalization rates of patients discharged from the hospital while being treated with risperidone, olanzapine, or conventional antipsychotics. METHOD: By using Israel's National Psychiatric Hospitalization Case Registry, rehospitalization status was monitored for all patients with schizophrenia who were discharged from any inpatient psychiatric facility in Israel while taking risperidone (N=268) or olanzapine (N=313) between Jan. 1, 1998, and Dec. 31, 1998, and a group of patients discharged during that time who were treated with conventional antipsychotics (N=458). Time to readmission over the course of 2 years was measured by the product-limit (Kaplan-Meier) formula. RESULTS: The readmission rate for patients discharged while taking conventional antipsychotics was higher than the rates for patients treated with either risperidone or olanzapine. At 24 months, 67% of the risperidone-treated patients and 69% of the olanzapine-treated patients remained in the community, as compared to 52% of the patients treated with conventional antipsychotics. CONCLUSIONS: This study suggests that the rehospitalization rates of patients taking the novel antipsychotics risperidone and olanzapine are not different from each other and are considerably lower than the rate for patients treated with conventional antipsychotics. The results confirm findings of previous studies suggesting that the levels of overall effectiveness of risperidone and olanzapine are not very different and offers evidence that these drugs are more effective in preventing rehospitalization than conventional antipsychotic drugs.     

Cognitive function and social abilities in patients with schizophrenia: relationship with atypical antipsychotics

Although atypical antipsychotics have been associated with improvements in cognitive function in schizophrenia, the neurochemical basis for such effects is not well understood. Candidate neurotransmitter systems primarily involve dopamine and serotonin. The current study explored this issue by examining the cognitive abilities, social function and quality of life in patients with schizophrenia who were medicated with atypical antipsychotics. Comparisons were done for matched schizophrenia patients who were on antipsychotics with (i) an affinity for multiple receptors (olanzapine, clozapine, quetiapine) versus those that have preferential affinity for dopamine receptors (risperidone, amisulpride); and patients on medication with (ii) a high affinity for serotonin (5HT-2A) receptors (risperidone, olanzapine, clozapine) versus those with a low (or no) affinity for 5HT-2A receptors (quetiapine, amisulpride). No differences emerged between groups on any cognitive or social variable when the groups were compared for the dopaminergic properties of antipsychotic medication. By contrast, differences did emerge when patients were compared on the 5HT-2A affinity of their antipsychotic medications. Patients on low 5HT-2A-affinity antipsychotics exhibited a better performance on a measure of selective attention and adjustment to living. These findings accord with the notion that serotonergic mechanisms are important determinants of both the cognitive and the social effects of the atypical antipsychotics.     

Rehospitalization Risk with Second-Generation and Depot Antipsychotics

Decreasing hospital admissions is important for improving outcomes for people with schizophrenia. Second-generation antipsychotics (SGAs) are better tolerated for long-term therapy than traditional medications and may contribute to a lower rehospitalization risk, but have not been compared to depot forms with regard to long-term outcomes. This study evaluates the risk of readmission in patients discharged from six State of Maryland inpatient mental health facilities between Jan. 1, 1997 and Dec. 31, 1997 on clozapine (N = 41), risperidone (N = 149), and olanzapine (N = 103). These patients were compared with those discharged from the two largest state facilities during the same time period on fluphenazine decanoate (N = 59) or haloperidol decanoate (N = 59). One-year readmission risk (measured by Kaplan–Meier survival analysis with Holm's adjustment for multiple comparison on Log Rank tests) were 10% for clozapine, 12% for risperidone, and 13% for olanzapine. These risks were not significantly lower than the readmission risk for fluphenazine decanoate (21%) but were significantly lower than haloperidol decanoate (35%) for all three SGAs. Demographic and clinical variables did not predict readmission for any of the medications. In patients with similar demographic and clinical characteristics, 1-year risk of readmission for patients treated with SGAs were at least comparable to the 1-year risk for patients receiving fluphenazine decanoate and lower than the risk for patients treated with haloperidol decanoate. SGAs may provide better long-term prognoses and outcomes for patients with schizophrenia.     

Olanzapine vs. other antipsychotics in actual out-patient settings: six months tolerability results from the European Schizophrenia Out-patient Health Outcomes study

OBJECTIVE: The European Schizophrenia Out-patient Health Outcomes study is an observational study investigating treatment in schizophrenia. We report treatment-emergent adverse events during the first 6 months of treatment. METHOD: The rate of extrapyramidal symptoms (EPS), anticholinergic use, weight gain and sexual related dysfunctions were assessed in 8,400 out-patients. RESULTS: Patients typical antipsychotics and risperidone experienced significantly more EPS and anticholinergic use than patients in the clozapine, olanzapine, and quetiapine cohorts. Patients treated with amisulpride, typical antipsychotics and risperidone were significantly more likely to have sexual related dysfunctions and/or amenorrhea. Increases in weight and body mass index occurred in all cohorts, but were significantly greater in the olanzapine and clozapine cohorts. CONCLUSION: Patients treated with olanzapine, quetiapine and clozapine had better tolerability outcomes regarding EPS and sexual related dysfunctions compared with patients receiving risperidone, amisulpride and typicals. Patients treated with olanzapine and clozapine had higher weight increases than patients treated with risperidone, quetiapine and typicals.     

Evaluating the CANSAS self-report (CANSAS-P) as a screening instrument for care needs in people with psychotic and affective disorders

The metabolic profiles of Chinese patients treated with second-generation antipsychotic (SGA) medication and first-generation antipsychotic (FGA) medication were compared. The sample comprised 99 patients treated with SGA (risperidone, olanzapine and ziprasidone) and 99 with FGA (chlorpromazine, haloperidol and trifluoperazine) from the outpatient clinic of a teaching hospital in Hong Kong. The most frequent psychiatric diagnosis was schizophrenia, followed by affective disorder and other psychiatric diagnoses. Subjects were measured for body weight, body height, fasting lipid and glucose levels. SGA was associated with higher LDL-cholesterol level than FGA. Individual comparison of different antipsychotics showed that patients on olanzapine had the greatest increases in cholesterol and triglycerides among all antipsychotics. The finding suggested SGA, particularly olanzapine, were associated with more metabolic risk factors than first-generation antipsychotics.     

Reduced serum BDNF levels in patients with chronic schizophrenic disorder in relapse,who were treated with typical or atypical antipsychotics

Brain-derived neurotrophic factor signals and dopaminergic function in the brain are strongly associated, and research on BDNF in schizophrenia may enhance our insights on the pathophysiological mechanisms of this disease. In the present study we aimed to investigate the possible association between serum BDNF levels and schizophrenic relapses and the possible differential effects of treatment with typical and atypical antipsychotics on serum BDNF levels in the same group of patients. We measured serum BDNF levels in 47 patients with schizophrenia during a relapse and again 6 weeks after administration of antipsychotic treatment (14 on risperidone, 18 on haloperidol, 10 on olanzapine and five on amisulpride) and in 44 healthy volunteers. Patients with schizophrenia showed reduced serum BDNF levels in relation to healthy volunteers at study entry. No significant differences were revealed in BDNF serum levels after 6 weeks of antipsychotic treatment in the patients compared to their own levels at study entry. However, serum BDNF was significantly increased in the subgroup receiving olanzapine compared to the other antipsychotics. Our findings may indicate a differential effect of olanzapine on BDNF levels compared to haloperidol, risperidone, and amisulpride.     

A meta-analysis of the efficacy of second-generation antipsychotics

BACKGROUND: Consensus panel recommendations regarding choice of an antipsychotic agent for schizophrenia differ markedly, but most consider second-generation antipsychotics (SGAs) as a homogeneous group. It has been suggested that SGAs seem falsely more efficacious than first-generation antipsychotics (FGAs) as a result of reduced efficacy due to use of a high-dose comparator, haloperidol. We performed (1) a meta-analysis of randomized efficacy trials comparing SGAs and FGAs, (2) comparisons between SGAs, (3) a dose-response analysis of FGAs and SGAs, and (4) an analysis of the effect on efficacy of an overly high dose of an FGA comparator. METHODS: Literature search of clinical trials between January 1953 and May 2002 of patients with schizophrenia from electronic databases, reference lists, posters, the Food and Drug Administration, and other unpublished data. We included 124 randomized controlled trials with efficacy data on 10 SGAs vs FGAs and 18 studies of comparisons between SGAs. Two of us independently extracted the sample sizes, means, and standard deviation of the efficacy data. RESULTS: Using the Hedges-Olkin algorithm, the effect sizes of clozapine, amisulpride, risperidone, and olanzapine were 0.49, 0.29, 0.25, and 0.21 greater than those of FGAs, with P values of 2 x 10-8, 3 x 10-7, 2 x 10-12, and 3 x 10-9, respectively. The remaining 6 SGAs were not significantly different from FGAs, although zotepine was marginally different. No efficacy difference was detected among amisulpride, risperidone, and olanzapine. We found no evidence that the haloperidol dose (or all FGA comparators converted to haloperidol-equivalent doses) affected these results when we examined its effect by drug or in a 2-way analysis of variance model in which SGA effectiveness is entered as a second factor. CONCLUSION: Some SGAs are more efficacious than FGAs, and, therefore, SGAs are not a homogeneous group.     

第二代抗精神病药对慢性精神分裂症患者的治疗作用

目的：探讨第1代抗精神病药（FGA）联合与未联合第2代抗精神病药（SGA）对慢性精神分裂症患者临床疗效、认知功能及社会功能的影响。方法：74例慢性精神分裂症患者被随机分为联合组和对照组,联合组为FGA联合SGA,对照组则为持续应用FGA,治疗至少12周。采用简明精神病量表（BPRS）分别于治疗前后评估患者临床疗效,以探究性眼动检测来评估患者的认知功能,采用个人和社会功能量表（PSP）评估社会功能。结果：探究性眼动检测治疗前凝视点数联合组显著低于对照组（P〈0.05）;尽管经过联合SGA治疗后两组间凝视点数虽不存在差异（P〉0.05）,但联合组治疗前后的凝视点数增加值却显著好于对照组（P〈0.001）;反应性探索（RSS）评分在疗前、疗后两组间均差异无显著性。所有联合SGA患者在治疗后PSP评分均显著优于未联合用药组（P〈0.05或P〈0.001）;LSD分析提示：尤以联合利培酮或阿立哌唑对患者PSP评分改善最为显著（P均〈0.001）。结论：联合SGA对慢性精神分裂症患者疗效显著,尤其对患者认知和社会功能改善明显。     

One-year rehospitalization rates of patients discharged on atypical versus conventional antipsychotics

This study examined one-year rehospitalization rates for patients who were discharged from Austin State Hospital between August 1, 1997, and July 31, 1998, while taking olanzapine, risperidone, or a conventional antipsychotic. Time to readmission was measured by the product-limit formula. Although conventional antipsychotics were associated with a lower rehospitalization rate, no significant difference in the one-year rehospitalization rate was observed between the groups. At 180 days after initial discharge, the patients who received olanzapine had a higher rate of rehospitalization than patients who were taking conventional antipsychotics. Conventional antipsychotics were associated with a lower one-year rehospitalization rate than risperidone or olanzapine.     

Conference report: Belgian consensus on metabolic problems associated with atypical antipsychotics

BACKGROUND: The current literature supports that schizophrenia (and bipolar disorders) appear to be associated with a higher prevalence of type 2 diabetes. Because of the silent nature of diabetes mellitus, and the fact that schizophrenic patients are not screened comprehensively for the disease, the true prevalence of hyperglycemia and diabetes may be substantially underestimated. Notably, it has been suggested that schizophrenia as such carries an increased risk, as certain characteristics of schizophrenic patients such as unhealthy life style promote the diabetes risk. LITERATURE FINDINGS: This risk may be increased by antipsychotic drug treatment, as was already suggested for first-generation antipsychotics (FGA). The amount of literature on the association of SGA and metabolic disorders is much larger however, although well-controlled prospective data are sparse. Reports comprise abnormal glucose regulation, exacerbation of existing type 1 and 2 diabetes, new-onset pseudo-type 1 or type 2 diabetes, diabetic ketoacidosis, coma and death. In large-scale studies (mostly retrospective), reviews and meta-analyses, the association was not found for all drugs. NEW DATA: According to recent reviews, the risk of developing diabetes was highest for clozapine and olanzapine, followed by quetiapine and risperidone. The hierarchy of liability of weight gain, or differential effects on insulin resistance was also in the described order. Apart from disturbances in glucose metabolism, further frequent metabolic abnormalities in schizophrenic patients on SGA include features of the metabolic syndrome. Antipsychotics such as clozapine and olanzapine have also been associated with hypertriglyceridemia, while agents such as haloperidol, risperidone and ziprasidone were associated with reductions in plasma triglycerides. Amisulpride, aripiprazole and ziprasidone seem to carry the lowest risk for weight gain, diabetes and effects on insulin resistance. CONCLUSION: As a consequence, there is a shift in attention toward physical health monitoring in patients with mental health disorders. The APA and ADA as well a British working group have recently published the findings on SGA and metabolic abnormalities in a joint statement (table I).     

Cerebral cortical gray expansion associated with two second-generation antipsychotics.

BACKGROUND: Second-generation antipsychotics (SGAs) differ from first-generation antipsychotics (FGAs) with respect to induction of less extrapyramidal morbidity, partially reducing negative symptoms, and causing modest improvement in neurocognitive functioning in patients with schizophrenia. SGAs demonstrate 5-HT2a antagonism. Differential effects of SGAs and FGAs on cortical gray volumes are explored herein. METHODS: Cerebral cortical gray was examined volumetrically in 19 patients with schizophrenia before and following 28 days of treatment with two SGAs (risperidone and ziprasidone; n = 13) or a FGA (haloperidol; n = 6). Seven (untreated) control subjects were also assessed at a similar interval. RESULTS: During treatment with the SGAs risperidone and ziprasidone, cerebral cortical gray of 13 patients with schizophrenia expanded 20.6 +/- 11.4 cc (p < .0005). Six patients receiving the FGA haloperidol, as well as 7 control subjects, showed no change in cortical gray volumes (p = .983 and p = .932, respectively) at the time of reassessment. CONCLUSIONS: Volumetric increase of cerebral cortical gray occurred early in the course of treatment with the SGAs ziprasidone and risperidone, but not with the FGA haloperidol. Such cortical gray expansion may be relevant to the reported enhanced neurocognition and quality of life associated with SGA treatment.     

Choosing antipsychotic maintenance therapy--a naturalistic study

Antipsychotic maintenance treatment is essential for preventing relapses of schizophrenia, but the variety of available antipsychotics may complicate the choice of drug. The aim of our naturalistic one-year follow-up study was to find out the factors predicting the choice of antipsychotics in discharged patients with schizophrenia or schizoaffective disorder and the predictors of one-year rehospitalization. The patients were receiving oral or depot classical antipsychotics or atypical agents clozapine or risperidone. Symptoms were assessed with Present State Examination. Included were 447 patients (202 males and 245 females) with a mean age of 39.1 years and 5.9 previous hospitalizations. The majority of patients (n = 322) were receiving depot antipsychotics and 43 were prescribed atypical agents. Two predictive models were built using the logistic regression analysis. Previously prescribed depot antipsychotics were positively related to further depot use, while patients who left the hospital against medical advice and those with slowness of speech at admission were less likely to receive depot drugs. On the other hand, previously used atypical antipsychotics and longer hospitalization predicted further use of atypical agents while patients discharged to community care facilities or nursing homes and those with more frequent previous hospitalizations were less likely to receive atypical agents. The Cox survival analysis showed the following one-year rehospitalization risk factors: diagnosis of schizoaffective disorder, frequent previous hospitalizations, inappropriate behavior, and oral classical antipsychotics versus depot or atypical agents. This study may yield some insight into the decision-making process in everyday clinical work regarding the choice of antipsychotic maintenance medication and its influence on rehospitalization rate.     

Service use and costs of treating schizophrenia with atypical antipsychotics

BACKGROUND: The high acquisition cost of the atypical antipsychotics has prompted their closer clinical and economic evaluation. This study aims to examine the financial implications of using atypical antipsychotics in a defined catchment area sample of patients with schizophrenia. METHOD: Service costs over a 10-month period were compared between groups of patients fulfilling DSM-IV criteria for schizophrenia who were taking different atypical antipsychotic agents. RESULTS: All patients studied were taking clozapine (N = 31). risperidone (N = 19), or olanzapine (N = 41). Clozapine was used in more chronic patients, while risperidone and olanzapine were prescribed in both chronic and recently diagnosed cases. After background group differences were controlled for, patients on risperidone treatment incurred the lowest costs. The monthly costs for the clozapine and olanzapine groups were higher than for risperidone by US $246 and US $566, respectively. CONCLUSION: Clozapine was reserved for more severe forms of schizophrenia, but its cost impact was relatively low. Risperidone, as prescribed in ordinary practice, may be more cost-effective than olanzapine.     

Second-Generation Antipsychotic Drugs and Extrapyramidal Side Effects: A Systematic Review and Meta-analysis of Head-to-Head Comparisons

Objective: While all second-generation antipsychotics (SGAs) are promoted for having a low risk of extrapyramidal side effects (EPS), clinical observations suggest differences between the various agents. Nevertheless, this question has never been examined in a systematic review and meta-analysis of head-to-head comparisons. Methods: We searched the register of the Cochrane schizophrenia group (last search May 2007), supplemented by MEDLINE (last search July 2009) for randomized, blinded studies comparing the following SGAs in the treatment of schizophrenia or related disorders: amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone, and zotepine. At least 3 reviewers extracted the data independently. The primary outcome was “use of antiparkinson medication.” The results were combined in a meta-analysis. Results: We included 54 studies with 116 arms. Risperidone was associated with more use of antiparkinson medication than clozapine, olanzapine, quetiapine, and ziprasidone. Ziprasidone showed more use of antiparkinson medication than olanzapine and quetiapine and zotepine more than clozapine. There was no significant difference between amisulpride and its comparators (olanzapine, risperidone, or ziprasidone). Quetiapine showed significantly less use of antiparkinson medication than the 3 other SGAs it was compared with (olanzapine, risperidone, and ziprasidone). Scale-derived data (Barnes Akathisia Scale and Simpson Angus Scale) were limited. Conclusions: Our meta-analysis demonstrates that there are differences between the SGAs in their ability to induce EPS that clinicians consider warrant treatment with antimuscarinic drugs. Even though the differences were relatively small, they might be important for individual patients and should be taken into account in drug choice.     

The new and evolving pharmacotherapy of schizophrenia.

Based on the evidence presented here, the following tentative conclusions can be drawn. Atypical antipsychotics (except amisulpride) have shown superiority over placebo in acute schizophrenia. Compared with conventional antipsychotics, they are at least as effective. Generally, analyses employing conservative criteria (e.g., Cochrane reviews) report few efficacy differences between atypical and conventional agents. There are now many well-controlled studies indicating modest advantages for the atypical antipsychotics, however, particularly in specific symptom domains. For the treatment of negative symptoms, olanzapine and to a lesser extent amisulpride seem most promising. Risperidone, olanzapine, and quetiapine display advantages in improving cognitive and depressive symptoms. There are indications that the atypical antipsychotics are associated with decreased likelihood of rehospitalization and improved quality of life. In head-to-head comparisons of atypical antipsychotics, none have shown consistent efficacy advantages. In severely refractory samples, no atypical antipsychotics have consistently been shown to be as effective as clozapine or superior to conventional agents. There are indications, however, that risperidone, olanzapine, and quetiapine have advantages over conventional agents in less severely refractory patients. Few maintenance RCTs have been published, and efficacy advantages for atypical antipsychotics in prospective RCTs in first-episode schizophrenia have not been reported.     

Effects of drop-out on efficacy estimates in five Cochrane reviews of popular antipsychotics for schizophrenia

Hutton P, Morrison AP, Yung AR, Taylor PJ, French P, Dunn G. Effects of drop‐out on efficacy estimates in five Cochrane reviews of popular antipsychotics for schizophrenia. Objective: Our aim was to find out how Cochrane reviews of five popular or frequently prescribed second‐generation antipsychotics in the UK (olanzapine, risperidone, quetiapine, amisulpride and aripiprazole) approached the problem of high drop‐out in placebo‐controlled trials. Method: We examined the following: (i) whether reviews included data from studies with a level of drop‐out exceeding their stated exclusion criterion; (ii) the level of missing data each efficacy outcome in each review relied upon; and (iii) impact of excluding studies with high drop‐out. Results: All reviews included data they stated they would exclude because of unacceptable levels of attrition, four (risperidone, olanzapine, amisulpride, aripiprazole) without clear acknowledgement or justification. Several reviews also excluded data from a number of relatively low‐attrition studies because of missing standard deviations. Conclusion: Cochrane reviews of five popular antipsychotics for schizophrenia misrepresented the available evidence on their efficacy. The impact of including high‐attrition studies was difficult to quantify because of the exclusion of relevant low‐attrition studies. Further analysis of the efficacy of these drugs in studies with acceptable rates of attrition is required. To reduce the problem of high attrition, trialists should gather follow‐up data from people who leave the double‐blind process early.     

Effectiveness and safety of antipsychotics in early onset psychoses: a long-term comparison

The effectiveness and safety of various antipsychotics was evaluated in a long-term study on 47 patients, 29 with schizophrenia and 18 with schizoaffective disorder, aged 10 to 17 years (mean 15.5) at onset. Follow-up ranged from 3 years (all 47 patients) to 11 years (19 patients). Data were collected on the following antipsychotics: haloperidol, risperidone, olanzapine, quetiapine, aripiprazole and clozapine. Cases with positive response were significantly more frequent with clozapine as compared to haloperidol, risperidone and olanzapine. Risperidone was significantly better than haloperidol at the 3-year follow-up. A comparison of the degree of clinical improvement evaluated with PANSS and CGI in patients treated with drugs in subsequent periods showed clozapine led to significantly greater improvement as compared to haloperidol, risperidone and olanzapine, and risperidone as compared to haloperidol. Data on long-term functioning significantly favored clozapine as compared to all the other drugs. Discontinuation due to side effects involved 20% patients with clozapine, lower percentage with the other drugs. The results of this study on early-onset schizophrenic and schizoaffective disorders confirm that even in the long-term, clozapine is more effective than haloperidol, risperidone and olanzapine. Despite a relevant incidence of adverse effects, clozapine seems to have unique effectiveness in treating children and adolescents with early-onset schizophrenic disorders.