换用阿立哌唑对精神分裂症患者代谢的影响

目的:探讨换用阿立哌唑治疗后精神分裂症患者各项代谢指标的改善情况。方法:选择43例换用阿立哌唑治疗的精神分裂症患者,分别在换药前和换药12周对患者的血糖、血脂和体质量等代谢指标进行检测。结果:换用阿立哌唑12周,患者的体质量(t=3.38,P<0.01)和体质量指数(t=3.07,P<0.01)显著改善,空腹血糖(t=2.96,P<0.01)、2h血糖(t=2.58,P<0.01)、糖化血红蛋白(t=3.50,P<0.01)、空腹胰岛素(t=19.71,P<0.01)、和稳态模型评估的胰岛素抵抗系数(t=2.70,P<0.05)均较治疗前显著降低,总胆固醇(t=2.78,P<0.01)、三酰甘油(t=4.38,P<0.01)和低密度脂蛋白(t=2.81,P<0.01)亦有显著降低,代谢综合征的患病率(χ2=19.07,P<0.01)显著降低。结论:换用阿立哌唑治疗对精神分裂症患者的代谢有显著改善作用。     

Prospective comparison of course of disability in antipsychotic‐treated and untreated schizophrenia patients

Objective: To compare the course of disability in schizophrenia patients receiving antipsychotics and those remaining untreated in a rural community. Method: Of 215 schizophrenia patients identified in a rural south Indian community, 58% were not receiving antipsychotics. Trained raters assessed the disability in 190 of these at baseline and after 1 year. The course of disability in those who remained untreated was compared with that in those who received antipsychotics. Results: Mean disability scores remained virtually unchanged in those who remained untreated, but showed a significant decline (indicating decrement in disability) in those who continued to receive antipsychotics and in those in whom antipsychotic treatment was initiated (P < 0.001; group × occasion effect). The proportion of patients classified as ‘disabled’ declined significantly in the treated group (P < 0.01), but remained the same in the untreated group. Conclusion: Disability in untreated schizophrenia patients remains unchanged over time. Treatment with antipsychotics in the community results in a considerable reduction in disability.     

Equally increased risk for metabolic syndrome in patients with bipolar disorder and schizophrenia treated with second-generation antipsychotics

Objective: Although second-generation antipsychotics (SGAs) are widely used in treating schizophrenia and bipolar disorder, their effects on dyslipidemia, glucose intolerance, metabolic syndrome (MetS), and coronary heart disease (CHD) risk are less well documented for bipolar disorder. We compared bipolar disorder and schizophrenia patients receiving SGAs to determine whether MetS prevalence is influenced by the primary psychiatric diagnosis or concomitant mood stabilizer treatment. Methods: Admission assessment of MetS criteria (abdominal obesity, fasting hypertriglyceridemia, low high-density lipoprotein cholesterol, hyperglycemia, arterial hypertension) and the calculated 10-year CHD risk in bipolar disorder and schizophrenia patients treated with SGAs and closely matched for age, sex, and race. Results: Compared to schizophrenia patients (n = 111), those with bipolar disorder (n = 74) had lower body mass index (27.1 ± 5.3 versus 29.9 ± 8.1, p = 0.0053), were more likely treated with mood stabilizers (60.8 versus 36.0, p = 0.0009), and less likely treated with clozapine (1.3% versus 15.3%, p = 0.0017) or two antipsychotics (10.8% versus 34.2%, p = 0.0003). Despite these differences, bipolar disorder and schizophrenia patients had comparable rates of MetS (43.2% versus 45.9%, p = 0.71) and predicted CHD events (10-year risk >10%: 18.9% versus 23.4%, p = 0.47). Using ≥100 mg/dL as the adapted glucose criterion, MetS rates were 54.0% in both diagnostic groups (p = 1.0). Mood stabilizer co-treatment was not associated with MetS or its individual criteria. Conclusions: Patients with bipolar disorder and schizophrenia who are treated with SGAs have similarly high rates of MetS. These findings suggest a shared susceptibility to antipsychotic-related metabolic dysregulations that is not primarily related to psychiatric diagnosis or concomitant mood stabilizer treatment.     

The METEOR study of diabetes and other metabolic disorders in patients with schizophrenia treated with antipsychotic drugs. I. Methodology

Patients with schizophrenia present a two‐ to three‐fold higher prevalence of diabetes, of metabolic syndrome and of cardiovascular morbidity. The reason for this increased prevalence may involve intrinsic vulnerability, lifestyle factors and iatrogenic effects of antipsychotic drugs. The objective of this multinational, cross‐sectional, pharmacoepidemiological study was to determine the prevalence of diabetes, lipid disorders, obesity, hypertension and the metabolic syndrome in patients with schizophrenia treated with antipsychotic drugs. Particular attention was taken to acquire data on a wide a range as possible of demographic, clinical and lifestyle variables that may influence the risk of metabolic disorders, which were taken into account in the calculation of prevalence data by propensity scoring. The study included 2270 subjects from 16 European countries, predominantly from Central and Eastern Europe. The proportion of subjects presenting the pathologies of interest was relatively high, ranging from 28% for glycaemic disorders to 70% for lipid disorders. Copyright © 2010 John Wiley & Sons, Ltd.     

氨磺必利替换奥氮平治疗对伴有代谢综合征精神分裂症患者的影响

目的:观察氨磺必利替换奥氮平治疗对伴有代谢综合征精神分裂症患者的影响。方法:92例奥氮平治疗伴代谢综合征的精神分裂症患者随机分为氨磺必利组(治疗组)及奥氮平组(对照组)各46例。治疗组在2周内将奥氮平换为氨磺必利,对照组维持奥氮平治疗,观察12周。入组时及第6、12周末测量腰围、血压、体质量指数(BMI)及空腹血糖(FBS)、高密度脂蛋白(HDL)、三酰甘油(TG)水平。应用阳性和阴性症状评定量表(PANSS)和治疗中出现的症状量表(TESS)进行疗效和安全性评定。结果:治疗12周末,治疗组腰围、收缩压、BMI、TG、FBS均显著低于对照组(P0.05或P0.01),两组PANSS评分差异无统计学意义(P0.05),而TESS评分治疗组低于对照组(P0.05)。结论:氨磺必利替换奥氮平治疗对精神分裂症患者体质量增加及代谢综合征有显著改善作用。     

Changes in metabolic parameters following a switch to aripiprazole in Japanese patients with schizophrenia: One-year follow-up study

The purpose of the present study was to evaluate changes in metabolic parameters after switching to aripiprazole in Japanese population. In this 1-year observation study, following a switch to aripiprazole, 32 patients with schizophrenia were observed and assessment was done of bodyweight, total cholesterol, triglyceride, serum prolactin level, and corrected QT (QTc) interval. Significant reductions were observed in these parameters other than QTc interval. Given known detrimental metabolic and hormonal effects of some atypical antipsychotics, a switch to aripiprazole may warrant serious consideration also in Asian patients who suffer those side-effects.     

Remission of severely impaired subjective wellbeing in 727 patients with schizophrenia treated with amisulpride

Studies of subjective wellbeing (SW) in schizophrenia have missed to define and to assess rate and predictors of SW response (SW-res) and SW remission (SW-rem). METHOD: A total of 727 patients with schizophrenia and severely impaired SW at entry (Subjective Wellbeing under Neuroleptics Scale, short version, SWN-K, total score < or =60) were treated with amisulpride over 12 weeks. SW-res was defined as SWN total score increase of at least 20% and by at least 10 points and SW-rem as total score of > or =80 points. RESULTS: Seventy percent fulfilled the SW-res criterion at week 4. At week 4 and week 12 (endpoint), the SW response criterion distinguished between patients with or without later SW remission and overall symptomatic and functional response. While 39% fulfilled the SW-rem criterion at endpoint, only 9.1% without early SW-res were in SW-rem at follow-up. Regression analyses indicated that SW-res was mainly predicted by greater severity of positive symptoms at baseline and SW-rem by lower severity of negative symptoms and better social functioning, and particularly by early SW-res. CONCLUSION: Patients with a risk of SW non-remission need to be identified early with subsequent treatment adaptation according to recommendations for incomplete remission and treatment resistance in schizophrenia.     

A double‐blind,placebo‐controlled trial of rosiglitazone for clozapine‐induced glucose metabolism impairment in patients with Schizophrenia

Objective: The primary purpose of this 8‐week double‐blind, placebo‐controlled trial of rosiglitazone 4 mg/day was to examine its effect on insulin sensitivity index (SI) and glucose utilization (SG) in clozapine‐treated subjects with schizophrenia with insulin resistance. Method: Eighteen subjects were randomized and accessed with a Frequently Sampled Intravenous Glucose Tolerance Test (FSIVGTT) at baseline and at week 8 to estimate SG and SI. Results: Controlling for the baseline, comparing the rosiglitazone group with placebo group, there was a non‐significant improvement in SG (0.016 ± 0.006–0.018 ± 0.008, effect size = 0.23, P = 0.05) with a trend of improvement in SI in the rosiglitazone group (4.6 ± 2.8–7.8 ± 6.7, effect size = 0.18, P = 0.08). There was a significant reduction in small low‐density lipoprotein cholesterol (LDL‐C) particle number (987 ± 443–694 ± 415, effect size = 0.30, P = 0.04). Conclusion: Rosiglitazone may have a role in addressing insulin resistance and lipid abnormalities associated with clozapine.     

10‐Year trends in the treatment and outcomes of patients with first‐episode schizophrenia

Nielsen J, le Quach P, Emborg C, Foldager L, Correll CU. 10‐Year trends in the treatment and outcomes of patients with first‐episode schizophrenia. Objective: The first episode of schizophrenia is a critical period for illness course and outcomes. We aimed to investigate treatments and outcomes during the first year after the diagnosis of schizophrenia. Method: Pharmacoepidemiologic inception cohort study of all newly diagnosed patients with schizophrenia in Denmark (n = 13 600) 1996–2005. Results: From 1996 to 2005, the mean age at first diagnosis decreased significantly (29.2–26.1 years), more patients received antipsychotics (67.2–80.7%, annual OR = 1.07, CI: 1.06–1.09, P < 0.001) and antipsychotic polypharmacy for >4 months (16.7–37.1%, OR = 1.14, CI: 1.12–1.57, P < 0.001). The antipsychotic defined daily dosage (DDD) doubled (150–332 DDD, P < 0.001), use of antidepressants (24.3–40.6%, P < 0.001). Bed days [89.9 days (CI: 81.8–98.8) to 71.8 days, CI: 63.7–80.8, P < 0.0001] decreased, whereas outpatient contacts [10.2 (CI: 9.5–11.0) to 21.4 (CI: 19.9–21.0), P < 0.0001] doubled. Conclusion: Between 1996 and 2005, there was an earlier recognition of schizophrenia, intensified outpatient treatment, increased use and dosing of antipsychotics and antidepressants, but also more antipsychotic polypharmacy.     

阿立哌唑对精神分裂症患者生活质量影响的研究

目的:探讨阿立哌唑、舒必利对精神分裂症患者生活质量的影响.方法:对70例精神分裂症患者随机分为两组,分别给予阿立哌唑和舒必利治疗.疗程3个月.用阳性症状与阴性症状量表(PANSS)评定精神症状,用世界卫生组织编制的生活质量量表(WHOQOL-100)评定生活质量.结果:治疗3个月后,阿立哌唑对精神分裂症阳性症状、阴性症状的改善和舒必利相似,两组间 PANSS 评分差异无显著性.阿立哌唑组 WHOQOL-100 各领域除精神支柱外均明显改善,在生活领域、心理领域、独立性领域、社会关系领域较舒必利有显著改善.结论:阿立哌唑组患者生活质量优于舒必利组.     

An economic evaluation of aripiprazole vs olanzapine adapted to the Italian setting using outcomes of metabolic syndrome and risk for diabetes in patients with schizophrenia

Objective

To evaluate the cost-effectiveness of aripiprazole and olanzapine in patients with schizophrenia.

Methods

Data from a double-blind, randomized study demonstrating the efficacy of aripiprazole and olanzapine were used to observe new incidence of metabolic syndrome (26-week therapy) and to model the risk of developing diabetes over 5 years of therapy. Cumulative incidence of metabolic syndrome was compared using Kaplan–Meier estimates; diabetes risk was estimated using a validated, general population risk-prediction model. Economic assessment was conducted from the third-party payer perspective by evaluating pharmacotherapy costs of treating schizophrenia and medical costs associated with treating adverse metabolic effects in a hypothetical cohort of 1000 patients. Resource utilization and costs were derived from the underlying study and published data, using a 3% rate to discount costs and benefits.

Results

For the patients switched from olanzapine to aripiprazole, treatment with aripiprazole was a dominant cost-saving strategy. Use of aripiprazole avoided 184 events of metabolic syndrome over 26 weeks of treatment, contributing to a real-world (RW) cost savings of €2.53 per patient and a total savings of approximately €465.52 over a 5-year period. For the same cohort, the risk-prediction model indicated that 34 occurrences of diabetes could be avoided over 5 years, corresponding to a RW cost savings of €56.86 per patient and a total saving of approximately €1,933.24. These savings reflect avoided costs in treating adverse metabolic events and comparable costs in the acquisition of aripiprazole.

Conclusions

Maintenance aripiprazole therapy offers medical and economic benefits over olanzapine, reflected by reduced incidence of metabolic syndrome and diabetes and associated lower costs.