Male sexual dysfunction and quality of life in schizophrenia

OBJECTIVE: To describe the prevalence and clinical correlates of sexual dysfunction in a sample of adult male outpatients with schizophrenia treated with olanzapine, risperidone, quetiapine, or haloperidol, focusing on associations between sexual dysfunction and patient-perceived quality of life. METHOD: Sexual dysfunction was assessed in 139 outpatients with DSM-IV schizophrenia who were receiving olanzapine, risperidone, quetiapine, or haloperidol, but no other medications associated with sexual side effects. Structured assessments were made of psychiatric symptoms, quality of life, and relationships. RESULTS: Sexual dysfunction occurred in 45.3% of patients. Patients with and without sexual dysfunction did not significantly differ with respect to severity of psychiatric symptoms. However, as compared with patients without sexual dysfunction, patients with sexual dysfunction reported significantly lower ratings on global quality of life (t = 2.4, df = 136, p = .02) and the level of enjoyment in their life (t = 2.5, df = 136, p = .01). Patients with sexual dysfunction were significantly less likely than those without sexual dysfunction to report having a romantic partner (17.5% vs. 43.4%; chi(2) = 10.7, df = 1, p = .001), though they were not significantly less likely to report difficulty making friends (27.0% vs. 32.9%; chi(2) = 0.57, df = 1, p = .45). Among patients with romantic partners, those with sexual dysfunction reported significantly poorer quality of their relationships (t = 2.3, df = 42, p = .02) and were less likely to talk to their partner about their illness (t = 2.0, df = 42, p = .047). CONCLUSIONS: Sexual dysfunction is common in men with schizophrenia who are treated with olanzapine, risperidone, quetiapine, or haloperidol and is associated with diminished quality of life, decreased occurrence of romantic relationships, and reduced intimacy when relationships are established. High prevalence and substantial interference with quality of life combine to make sexual dysfunction an important area for clinical assessment and appropriate intervention in the community management of schizophrenia.     

Sexual dysfunction associated with second-generation antipsychotics in outpatients with schizophrenia or schizoaffective disorder: an empirical evaluation of olanzapine, risperidone, and quetiapine

OBJECTIVE: Evaluate sexual dysfunction, as measured by the Arizona Sexual Experience Scale (ASEX), in olanzapine-, quetiapine-, and risperidone-treated outpatients with schizophrenia or schizoaffective disorder. METHOD: The sexual functioning of 238 outpatients (age> or =18 years) with diagnoses of schizophrenia or schizoaffective disorder who took quetiapine (n=57), olanzapine (n=94), or risperidone (n=87) was evaluated with a one-time rating of the ASEX. The dose range for each treatment group was 5 to 40 mg/day (M=16.6 mg/day, SD=7.4) for olanzapine; 1 to 8 mg/day (M=3.9 mg/day, SD=1.6) for risperidone; and 50 to 900 mg/day (M=376.8 mg/day, SD=213.4) for quetiapine. Antipsychotic group designation was based on medication treatment at study entry (i.e., non-random assignment). Participant characteristics were collected to test for treatment group differences and for potential associations with severity of sexual dysfunction. The primary data analysis was a mixed linear model analysis of covariance with age, gender, and presence/absence of antidepressant known to cause sexual dysfunction included as covariates. RESULTS: There was a significant treatment effect on severity of sexual dysfunction, as measured by ASEX total scores (p=.04). The adjusted average ASEX total scores were lower in the quetiapine (M=17.80) than in the risperidone (M=19.69) or olanzapine (M=20.34) groups. Individual comparisons of the treatments on adjusted average ASEX total scores indicated a significant difference between olanzapine and quetiapine (p=.04), but no difference between risperidone and quetiapine (p=.17) or olanzapine and risperidone (p=.76). CONCLUSIONS: Quetiapine was associated with less severe sexual dysfunction than olanzapine and risperidone (albeit the effect between risperidone and quetiapine was not statistically significant). Olanzapine and risperidone were associated with a comparable degree of sexual dysfunction. Patients in all three treatment groups, nonetheless, experienced a moderately high degree of sexual dysfunction. Because the patients were not randomized, conclusions must be interpreted within the context of the quasi-experimental design.     

Effectiveness of olanzapine, quetiapine, risperidone, and ziprasidone in patients with chronic schizophrenia following discontinuation of a previous atypical antipsychotic

BACKGROUND: In the treatment of schizophrenia, changing antipsychotics is common when one treatment is suboptimally effective, but the relative effectiveness of drugs used in this strategy is unknown. This randomized, double-blind study compared olanzapine, quetiapine, risperidone, and ziprasidone in patients who had just discontinued a different atypical antipsychotic. METHOD: Subjects with schizophrenia (N=444) who had discontinued the atypical antipsychotic randomly assigned during phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) investigation were randomly reassigned to double-blind treatment with a different antipsychotic (olanzapine, 7.5-30 mg/day [N=66]; quetiapine, 200-800 mg/day [N=63]; risperidone, 1.5-6.0 mg/day [N=69]; or ziprasidone, 40-160 mg/day [N=135]). The primary aim was to determine if there were differences between these four treatments in effectiveness measured by time until discontinuation for any reason. RESULTS: The time to treatment discontinuation was longer for patients treated with risperidone (median: 7.0 months) and olanzapine (6.3 months) than with quetiapine (4.0 months) and ziprasidone (2.8 months). Among patients who discontinued their previous antipsychotic because of inefficacy (N=184), olanzapine was more effective than quetiapine and ziprasidone, and risperidone was more effective than quetiapine. There were no significant differences between antipsychotics among those who discontinued their previous treatment because of intolerability (N=168). CONCLUSIONS: Among this group of patients with chronic schizophrenia who had just discontinued treatment with an atypical antipsychotic, risperidone and olanzapine were more effective than quetiapine and ziprasidone as reflected by longer time until discontinuation for any reason.     

Effectiveness of antipsychotic treatments for schizophrenia: interim 6-month analysis from a prospective observational study (IC-SOHO) comparing olanzapine, quetiapine, risperidone, and haloperidol

BACKGROUND: 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. METHOD: 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. RESULTS: 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). CONCLUSION: Our results support the previously reported positive impact of atypical antipsychotics, particularly olanzapine, in patients with schizophrenia.     

Effectiveness of clozapine, olanzapine, quetiapine, risperidone, and haloperidol monotherapy in reducing hostile and aggressive behavior in outpatients treated for schizophrenia: a prospective naturalistic study (IC-SOHO).

OBJECTIVE: Antipsychotic medications may reduce hostile and aggressive behavior in schizophrenia. This study compared the effectiveness of antipsychotics in the treatment of aggression. METHOD: The Intercontinental Schizophrenia Outpatient Health Outcomes (IC-SOHO) study compares the effectiveness of antipsychotic treatments in practice setting. Schizophrenia outpatients who initiated or changed to a new antipsychotic are followed in this non-interventional, prospective observational study for up to 3 years, with 6-months data now available on the entire cohort (N=7655). The presence or absence of verbal or physical hostility/aggression was assessed retrospectively for the period of 6 months before enrollment, and prospectively in the period of 6 months after enrollment (the study treatment period). At baseline, patients in five monotherapy treatment groups (combined N=3135) were prescribed one of the treatments: clozapine, olanzapine, quetiapine, risperidone, or haloperidol, and had complete data. RESULTS: Hostile/aggressive behavior was reduced during the treatment period. Olanzapine and risperidone were significantly superior to haloperidol and to clozapine in this respect. These results remained essentially unchanged when adjusting for baseline imbalances in age, gender, age of onset, and substance abuse. CONCLUSIONS: As monotherapy, both olanzapine and risperidone were superior to haloperidol and clozapine in reducing aggression. The relative lack of effectiveness of clozapine may be specific to this study population.     

Weight gain in patients with schizophrenia treated with risperidone,olanzapine, quetiapine or haloperidol: results of the EIRE study

OBJECTIVES: The aim of this cross-sectional study, the EIRE study, was to assess the frequency of several side effects with antipsychotics in the clinical setting. This paper addresses the adverse effect of weight gain. METHOD: Outpatients diagnosed of schizophrenia according to DSM-IV criteria and receiving a single antipsychotic (risperidone, olanzapine, quetiapine or haloperidol) for at least 4 weeks were consecutively recruited. Data were collected in a single visit, including data on demographic, clinical and treatment characteristics. Mean weight change was evaluated retrospectively by means of clinical charts and the weight at the time of the visit; in addition, the corresponding item of a modified version of the UKU, a Scandinavian side-effect rating scale, was used. Chi-squared test and logistic regression methods were used to analyze frequency of weight gain between treatments. RESULTS: Out of 669 recruited, 636 evaluable patients were assessed. The treatment with the highest number of patients with weight gain as an adverse reaction on the UKU scale was olanzapine (74.5%), followed by risperidone (53.4%) and haloperidol (40.0%). The proportion of patients with clinically relevant weight gain (>or=7% increase versus initial weight) was also higher with olanzapine (45.7%) than with risperidone (30.6%) and haloperidol (22.4%). Five patients (13.5%) treated with quetiapine had some degree of weight gain according to the UKU scale, although no patient showed a clinically relevant weight gain (>or=7%). Treatment with olanzapine and risperidone were identified as risk factors of weight gain versus haloperidol. The risk of weight gain was higher in women (OR: 4.4), overweight patients (OR: 3.0) and in patients with 相似文献   

Safety and efficacy of long-acting risperidone in schizophrenia: a 12-week, multicenter, open-label study in stable patients switched from typical and atypical oral antipsychotics

BACKGROUND: The safety and efficacy of the first long-acting injectable atypical antipsychotic, risperidone, were assessed in stable patients with schizophrenia switched from oral antipsychotic medications. METHOD: Data were collected between July 1, 2001, and October 25, 2002. The study population included patients from clinics, hospitals, and physicians' offices. After a 4-week run-in period, symptomatically stable patients with schizophrenia (DSM-IV) who had been taking haloperidol (N = 46), quetiapine (N = 45), or olanzapine (N = 50) received 25 mg of long-acting risperidone. The oral antipsychotics were continued for 3 weeks after the first injection of long-acting risperidone. Injections were administered every 2 weeks at 25 mg up to a maximum dose of 50 mg for 12 weeks in this multicenter, open-label study. RESULTS: Long-acting risperidone was well tolerated. Of the 141 patients who participated in the study, the most frequently reported adverse events were insomnia (16%), headache (15%), psychosis (11%), and agitation (11%). The mean increase in body weight was 0.4 kg. No other clinically relevant laboratory abnormalities or significant electrocardiogram changes were observed during the 12-week treatment. Extrapyramidal Symptom Rating Scale total scores were reduced during treatment with long-acting risperidone. Improvements in symptoms of schizophrenia were observed with long-acting risperidone at week 4 and continued through the 12-week treatment with significant reductions in total Positive and Negative Syndrome Scale (PANSS) scores at week 8 (-2.5, p <.01) and week 12 (-3.9, p <.001). At endpoint, 37% (50/135) of these stable patients were rated as clinically improved (> or = 20% decrease in PANSS total scores). CONCLUSIONS: Switching treatment from oral antipsychotics to long-acting risperidone without an intervening period of oral risperidone was safe and well tolerated. Long-acting risperidone also significantly reduced the severity of symptoms in these stable 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.     

Ethnicity and prescription patterns for haloperidol, risperidone, and olanzapine

OBJECTIVE: Patients with schizophrenia may respond better to second-generation antipsychotics than to older antipsychotics because of their superior efficacy and safety profiles. However, the reduced likelihood among ethnic minority groups of receiving newer antipsychotics may be associated with reduced medication adherence and health service use, potentially contributing to poor response rates. This study examined whether ethnicity helped predict whether patients with schizophrenia were given a first- or a second-generation antipsychotic, haloperidol versus risperidone or olanzapine, and what type of second-generation antipsychotic was prescribed, risperidone or olanzapine, when other factors were controlled for. METHODS: Texas Medicaid claims were analyzed for persons aged 21 to 65 years with a diagnosis of schizophrenia or schizoaffective disorder who started treatment with olanzapine (N=1875), risperidone (N=982), or haloperidol (N= 726) between January 1, 1997 and August 31, 1998. The association between antipsychotic prescribing patterns among African Americans, Mexican Americans, and whites was assessed by using logistic regression analysis. Covariates included other patient demographic characteristics, region, comorbid mental health conditions, and medication and health care resource use in the 12 months before antipsychotic initiation. RESULTS: The results of the first- versus second-generation antipsychotic analysis indicated that African Americans were significantly less likely than whites to receive risperidone or olanzapine. Although not statistically significant, the odds ratio indicated that Mexican Americans were also less likely to receive risperidone or olanzapine. Ethnicity was not associated with significant differences in the prescribing patterns of risperidone versus olanzapine. CONCLUSIONS: When other factors were controlled for, African Americans were significantly less likely to receive the newer antipsychotics. Among those who received the newer antipsychotics, ethnicity did not affect medication choice.     

The PsyCoLaus study: methodology and characteristics of the sample of a population-based survey on psychiatric disorders and their association with genetic and cardiovascular risk factors

Background

How long an antipsychotic is effective in maintaining response is important in choosing the correct treatment for people with schizophrenia. This post-hoc analysis describes maintenance of response over 24 or 28 weeks in people treated for schizophrenia with olanzapine, risperidone, quetiapine, ziprasidone, or aripiprazole.

Methods

This was a post-hoc analysis using data from 5 double-blind, randomized, comparative trials of 24 or 28 weeks duration in which olanzapine was compared to risperidone (1 study; N = 339), quetiapine (1 study; N = 346), ziprasidone (2 studies; N = 548 and 394) or aripiprazole (1 study; N = 566) for treatment of schizophrenia. For each study, time to loss of response in patients who met criteria for response at Week 8 and the proportion of patients who lost response following Week 8 were compared by treatment group. The number needed to treat (NNT) with olanzapine rather than comparator to avoid loss of one additional responder over 24 or 28 weeks of treatment was calculated for each study.

Results

Time maintained in response was significantly longer (p < .05) for olanzapine compared to risperidone, quetiapine, and ziprasidone. Olanzapine did not significantly differ from aripiprazole. The proportion of patients who lost response was significantly lower for olanzapine versus risperidone, quetiapine, and ziprasidone (p < .05). NNTs to avoid one additional patient with loss of response with olanzapine versus risperidone, quetiapine and ziprasidone were favourable, ranging from 5 to 9.

Conclusion

During 24 and 28 weeks of treatment, the antipsychotics studied differed in the time that treated patients with schizophrenia remained in response and the proportion of patients who lost response. Olanzapine treatment resulted in a consistent and statistically significant advantage in maintenance of response compared to treatment with risperidone, quetiapine and ziprasidone; but not compared to treatment with aripiprazole.     

Serum leptin and triglyceride levels in patients on treatment with atypical antipsychotics

BACKGROUND: Weight gain is a common adverse effect associated with the use of most antipsychotic drugs. Leptin has been reported to be associated with antipsychotic-induced weight gain. Previous studies have demonstrated a relationship between the atypical antipsychotics clozapine and olanzapine and serum leptin levels. We planned to comparatively investigate the effects of the atypical antipsychotics quetiapine, olanzapine, risperidone, and clozapine on leptin and triglyceride levels and weight gain. METHOD: The study population comprised 56 patients with DSM-IV schizophrenia, who were divided into 4 treatment groups: quetiapine (N = 14), olanzapine (N = 14), risperidone (N = 14), or clozapine (N = 14) monotherapy, and a control group of 11 patients receiving no psychopharmacologic treatment. The patients were evaluated at baseline and at the sixth week according to the Positive and Negative Syndrome Scale (PANSS), body mass index (BMI), weight, and fasting serum leptin and triglyceride levels. Data were gathered in 2001 and 2002. RESULTS: Olanzapine and clozapine caused a marked increase in weight and serum triglyceride and leptin levels, though increases in these variables were modest in the patients receiving quetiapine and minimal in those receiving risperidone. There were positive correlations between serum leptin levels and BMI and triglyceride levels. Clinical efficacy, as indicated by decrease in total PANSS scores, was associated with leptin levels in all atypical antipsychotic groups. CONCLUSION: Our results suggest that leptin may be associated with olanzapine- and clozapine-induced weight gain and that quetiapine appears to have modest influence and risperidone appears to have minimal influence on leptin and triglyceride levels and weight gain compared with olanzapine and clozapine.     

Effectiveness of olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia after discontinuing perphenazine: a CATIE study

OBJECTIVE: The relative effectiveness of newly started antipsychotic drugs for individuals with schizophrenia may depend on multiple factors, including each patient's previous treatment response and the reason for a new medication trial. This randomized, double-blind study compared olanzapine, quetiapine, and risperidone in patients who had just discontinued the older antipsychotic perphenazine. METHOD: Subjects with schizophrenia (N=114) who had been randomly assigned to and then discontinued perphenazine in phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia study were reassigned randomly to double-blinded treatment with olanzapine, 7.5-30.0 mg/day (N=38); quetiapine, 200-800 mg/day (N=38); or risperidone, 1.5-6.0 mg/day (N=38). The primary aim was to determine whether there were differences among these three treatments in effectiveness, as measured by time to treatment discontinuation for any reason. Secondary outcomes included reasons for treatment discontinuation and measures of drug tolerability. RESULTS: The time to treatment discontinuation was longer for patients treated with quetiapine (median, 9.9 months) and olanzapine (7.1 months) than with risperidone (3.6 months). There were no significant differences between treatments on discontinuation due to inefficacy, intolerability, or patient decision. CONCLUSIONS: Among this group of patients with chronic schizophrenia who had just discontinued the older antipsychotic perphenazine, quetiapine and olanzapine were more effective than risperidone, as reflected by longer time to discontinuation for any reason. In the context of other results from the CATIE study, the effectiveness and acceptability of antipsychotic drugs appears to vary considerably according to clinical circumstances.     

Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment

OBJECTIVE: When a schizophrenia patient has an inadequate response to treatment with an antipsychotic drug, it is unclear what other antipsychotic to switch to and when to use clozapine. In this study, the authors compared switching to clozapine with switching to another atypical antipsychotic in patients who had discontinued treatment with a newer atypical antipsychotic in the context of the Clinical Antipsychotic Trials for Interventions Effectiveness (CATIE) investigation. METHOD: Ninety-nine patients who discontinued treatment with olanzapine, quetiapine, risperidone, or ziprasidone in phase 1 or 1B of the trials, primarily because of inadequate efficacy, were randomly assigned to open-label treatment with clozapine (N=49) or blinded treatment with another newer atypical antipsychotic not previously received in the trial (olanzapine [N=19], quetiapine [N=15], or risperidone [N=16]). RESULTS: Time until treatment discontinuation for any reason was significantly longer for clozapine (median=10.5 months) than for quetiapine (median=3.3), or risperidone (median=2.8), but not for olanzapine (median=2.7). Time to discontinuation because of inadequate therapeutic effect was significantly longer for clozapine than for olanzapine, quetiapine, or risperidone. At 3-month assessments, Positive and Negative Syndrome Scale total scores had decreased more in patients treated with clozapine than in patients treated with quetiapine or risperidone but not olanzapine. One patient treated with clozapine developed agranulocytosis, and another developed eosinophilia; both required treatment discontinuation. CONCLUSIONS: For these patients with schizophrenia who prospectively failed to improve with an atypical antipsychotic, clozapine was more effective than switching to another newer atypical antipsychotic. Safety monitoring is necessary to detect and manage clozapine's serious side effects.     

The Schizophrenia Outpatient Health Outcomes (SOHO) study: 3-year results of antipsychotic treatment discontinuation and related clinical factors in Spain.

INTRODUCTION: This article presents the long-term results in terms of antipsychotic medication maintenance and factors influencing it in a representative sample of patients with schizophrenia recruited in the SOHO study within Spain. METHODS: The SOHO was a prospective, 3-year observational study of the outcomes of schizophrenia treatment in outpatients who initiated therapy or changed to a new antipsychotic performed in 10 European countries with a focus on olanzapine. The Kaplan-Meier method was used to analyse the time to treatment discontinuation and the Cox proportional hazards model to investigate correlates of discontinuation. RESULTS AND CONCLUSIONS: In total, 1688 patients were included in the analyses. Medication maintenance at 3years varied with the antipsychotic prescribed, being highest with clozapine (57.6%, 95% CI 39.2-74.5), followed by olanzapine (48.3%, 95% CI 45.1-51.5); and lowest with quetiapine (19.0%, 95% CI 13.0-26.3). Treatment discontinuation was significantly less frequent with olanzapine than with risperidone (p=0.015), depot typical (p=0.001), oral typical antipsychotics (p<0.001) or quetiapine (p<0.001); but not than with clozapine (p=0.309). Longer maintenance was also associated with higher social abilities and better cognitive status at baseline; in contrast, a shorter time to discontinuation was associated with the need for mood stabilisers during follow-up. This study emphasises the different value of antipsychotics in day-to-day clinical practice, as some of them were associated with longer medication maintenance periods than others. This study has some limitations because of possible selection and information biases derived from the non-systematic, non-randomised allocation to treatments and the existence of unobserved covariates that may influence the outcome.     

Equivalent occupancy of dopamine D1 and D2 receptors with clozapine: differentiation from other atypical antipsychotics

OBJECTIVE: Clozapine, the prototype of atypical antipsychotics, remains unique in its efficacy in the treatment of refractory schizophrenia. Its affinity for dopamine D(4) receptors, serotonin 5-HT(2A) receptor antagonism, effects on the noradrenergic system, and its relatively moderate occupancy of D(2) receptors are unlikely to be the critical mechanism underlying its efficacy. In an attempt to elucidate the molecular/synaptic mechanism underlying clozapine's distinctiveness in refractory schizophrenia, the authors studied the in vivo D(1) and D(2) receptor profile of clozapine compared with other atypical antipsychotics. METHOD: Positron emission tomography with the radioligands [(11)C]SCH23390 and [(11)C]raclopride was used to investigate D(1) and D(2) receptor occupancy in vivo in 25 schizophrenia patients receiving atypical antipsychotic treatment with clozapine, olanzapine, quetiapine, or risperidone. RESULTS: Mean striatal D(1) occupancies ranged from 55% with clozapine to 12% with quetiapine (rank order: clozapine > olanzapine > risperidone > quetiapine). The striatal D(2) occupancy ranged from 81% with risperidone to 30% with quetiapine (rank order: risperidone > olanzapine > clozapine > quetiapine). The ratio of striatal D(1)/D(2) occupancy was significantly higher for clozapine (0.88) relative to olanzapine (0.54), quetiapine (0.41), or risperidone (0.31). CONCLUSIONS: Among the atypical antipsychotics, clozapine appears to have a simultaneous and equivalent occupancy of dopamine D(1) and D(2) receptors. Whether its effect on D(1) receptors represents agonism or antagonism is not yet clear, as this issue is still unresolved in the preclinical arena. This distinctive effect on D(1)/D(2) receptors may be responsible for clozapine's unique effectiveness in patients with schizophrenia refractory to other typical and atypical antipsychotics.     

Lower mortality in geriatric patients receiving risperidone and olanzapine versus haloperidol: preliminary analysis of retrospective data.

OBJECTIVE: The authors examined the mortality rate in geriatric patients receiving either haloperidol or atypical antipsychotics. METHODS: Authors tracked mortality over a 2-year period in patients age 65 years or older receiving haloperidol (N=299) or the atypical antipsychotics risperidone or olanzapine (N= 1,254). RESULTS: Sixty-four patients in the haloperidol group (21.4%) and 61 patients in the atypical group (4.75%) died during the 2-year study period. The difference was statistically significant. CONCLUSIONS: The findings suggest that mortality in elderly patients receiving haloperidol is significantly higher than in those receiving the atypical antipsychotics risperidone or olanzapine. Authors discuss possible causal mechanisms.     

利培酮、奥氮平和喹硫平治疗未服药的精神分裂症患者的疗效和不良反应：1年自然观察研究

背景第二代抗精神病药被日益广泛地用于治疗精神分裂症首次发作,但其疗效是否一致尚有争议。假设利培酮、奥氮平、喹硫平治疗未服药的首次发病的精神分裂症或分裂样精神障碍患者,其1年的疗效是一致的。方法采用自然观察研究方法,对病程≤5年,符合ICD-10精神分裂症或分裂样精神障碍研究用诊断标准的未服药门诊患者随访1年。纳入398例患者,分别用利培酮（131例）、奥氮平（136例）、喹硫平（131例）单药治疗。在开始治疗后的第2周,2、3、6、8以及12个月时采用阳性与阴性综合征量表（Positive and Negative Syndrome Scale,PANSS）评估疗效,用副反应量表（Treatment Emergent Symptom Scale,TESS）评估治疗中出现的不良反应,非盲法评定。结果共269例（67%）患者完成1年随访。利培酮组、奥氮平组和喹硫平组的停药率分别为35.1%（46/131）、31.6%（43/136）和32.1%（42/131）,χ^2=0.43,P=0.809。对脱落患者的资料采用末次观察结转法,1年时利培酮组、奥氮平组和喹硫平组的PANSS总分平均值（标准差）分别减少46.8%（17.0%）,48.6%（19.6%）和47.3%（16.2%）,F=0.38,P=0.688。重复测量的方差分析显示,无论是PANSS总分还是分量表分,治疗各时点三组间差异均无统计学意义。治疗第2周时利培酮组发生震颤和静坐不能的比例高于其他两组。1年时,3组中常见的不良反应是体重增加和嗜睡,奥氮平组体重增加的比例（69.9%）高于其他两组。根据持续存在不良反应症状的时点数与总随访时点数的比值衡量不良反应的持续时间,锥体外系症状在利培酮组最明显,体重增加在奥氮平组最明显,心动过速在喹硫平组最明显。结论利培酮、奥氮平、喹硫平单药治疗未服药的精神分裂症或分裂样精神障碍患者1年疗效相似,但不良反应有所不同。     

Oral risperidone, olanzapine and quetiapine versus haloperidol in psychotic agitation

PURPOSE: Acute agitation is a common presentation in emergency departments and is often secondary to an underlying psychotic condition. The aim of this study was to compare the effectiveness of three second generation antipsychotics (risperidone, olanzapine, quetiapine) versus haloperidol in the treatment of psychotic agitation for up to 72 h. GENERAL METHODS: We recruited 101 patients with acute psychosis who were admitted at the Mental Health Department 1 South of Turin, Psychiatric Emergency Service of San Giovanni Battista Hospital, from June 2004 to June 2005. FINDINGS: Aggressive behavior, as measured by Modified Overt Aggression Scale and Hostility-suspiciousness factor derived from the Brief Psychiatric Rating Scale, significantly improved in all groups, with no significant between-group differences. Extrapyramidal symptoms were more common in haloperidol treated patients compared with patients receiving risperidone, olanzapine or quetiapine. CONCLUSIONS: Our results show that in the clinical practice setting of emergency psychiatry olanzapine, risperidone, quetiapine are as effective as haloperidol and better tolerated.     

Antipsychotic use in the treatment of outpatients with schizophrenia in the VA from fiscal years 1999 to 2006

OBJECTIVE: This study examined changes in prescribing patterns of antipsychotic medications to treat schizophrenia. METHODS: Pharmacy records for patients with schizophrenia were obtained from Department of Veterans Affairs databases. The proportion of patients prescribed specific second-generation antipsychotics or any first-generation antipsychotic was calculated per year. RESULTS: In fiscal year (FY) 2006, 78,849 veterans with schizophrenia were prescribed antipsychotic medication. For FY 1999 to FY 2006 the percentage of patients with schizophrenia who received first-generation antipsychotics decreased from 40.8% to 15.9%, but the percentage receiving olanzapine, after peaking at 32.0% in FY 2001, decreased to 19.0%. The percentage of patients given quetiapine increased from 2.5% to 18.8%; risperidone, from 25.5% to 29.7%. However, clozapine usage remained flat, at 2.0%-3.0%. Use of then-new ziprasidone and aripiprazole rose from 5.0% to 9.0%. CONCLUSIONS: Use of each antipsychotic newly marketed over eight years increased while use of risperidone was unchanged and use of olanzapine and the first-generation antipsychotics declined.