奥氮平联合金刚烷胺治疗精神分裂症首次发病患者的随机双盲对照研究

目的:探讨金刚烷胺添加对奥氮平治疗精神分裂症首次发病患者疗效及脂代谢的影响。方法:采用随机双盲法,将61例精神分裂症首次发病的患者随机分为研究组(31例)和对照组(30例),在奥氮平治疗的基础上,研究组及对照组分别添加金刚烷胺200 mg/d及安慰剂;疗程8周。治疗前及治疗4、8周进行阳性和阴性症状量表(PANSS)及治疗过程中出现的症状量表(TESS)评定,测量体质量,检测血三酰甘油(TG)、低密度脂蛋白(LDL)、总胆固醇(TC)水平。结果:治疗后研究组PANSS阴性症状减分值显著大于对照组(P0.05);TESS评分两组间差异无统计学意义;两组体质量和TG增加值差异无统计学意义;对照组LDL、TC增加值显著大于研究组(P均0.05)。结论:添加小剂量金刚烷胺短期内可明显增加奥氮平对精神分裂症患者阴性症状的改善作用,减少血LDL和TC水平升高;但不能改善奥氮平所致的体质量增加。     

阿立哌唑对奥氮平所致女性精神分裂症患者泌乳素、体质量增加的影响

正精神分裂症是精神科常见的病因未明的严重精神疾病;目前尚无根治手段,主要以长期服药控制精神症状达到康复的目的。使用最为广泛的是第二代抗精神病药,较之第一代抗精神病药明显减少了锥体外系反应,但其引起的代谢、体质量及内分泌异常等不良反应也越来越引起重视。奥氮平是第二代抗精神病药的代表之一,临床应用广泛,但容易引起嗜睡、体质量增加,泌乳素增高等内分泌变化。本研究采用自身对照方法,观察小剂量阿立哌唑对奥氮平所致女性精神分裂症患者泌乳素、体质量增高的影响。1对象和方法患者为2015年6～12月在本中心住院治疗及出院后完     

奥氮平治疗精神分裂症对照研究的Meta分析

目的：探讨奥氮平治疗精神分裂症的疗效和不良反应。方法：应用M eta分析对17篇奥氮平与其他抗精神病药治疗精神分裂症对照研究的文章进行再分析。结果：奥氮平自身对照比较的治疗效应极大（χ^2=141.00,P〈0.05）。治疗2周和治疗结束,奥氮平与对照药疗效比较差异无显著性（P〉0.05）;阳性与阴性症状量表（PANSS）评分比较差异亦无显著性（P〉0.05）。与对照药相比,奥氮平的不良反应显著少于对照药组（P〈0.05或P〈0.01）。结论：奥氮平与对照药的临床疗效相仿,但不良反应明显较少。     

奥氮平治疗精神分裂症阴性症状对照研究的Meta分析

目的探讨奥氮平治疗精神分裂症阴性症状的疗效和不良反应的差异。方法应用Meta分析对13项奥氮平与其他抗精神病药物治疗精神分裂症阴性症状对照研究的文章进行再分析，评价其合并效应量大小和综合显著性检验。结果1．奥氮平治疗前后的自身对照，合并效应量d=-2．77，95％CI（-4．83，-0．70），Х^2=89．03，P〈0．01；2．奥氮平与对照药物在第2周末和治疗后组间的比较，分别为d=-0．14，95%ACI（-0．31，0．04），Х^2=4．56，P〉0．05；Y合并=-0．10，95％CI（-0．22，0．03），Х^2=3．20，P〉0．05；提示两组疗效没有显著差异；3．奥氮平的不良反应显著少于对照组药物。结论奥氮平与对照组的疗效相仿，但副作用少。     

中国大陆地区精神分裂症患者奥氮平治疗引起体质量增加的相关因素分析

目的 分析中国大陆地区精神分裂症患者奥氮平治疗期间体质量增加的相关因素.方法 采用事后分析方法,对1项多国家及地区关于奥氮平治疗的观察性研究中国大陆地区330例精神分裂症患者的临床数据进行分析.结果 奥氮平治疗6个月,中国大陆地区患者平均体质量增加(4.5±4.0)kg,145例(47.2%)患者出现有临床意义的体质量...     

二甲双胍对奥氮平所致精神分裂症患者体质量增加的影响

目的 验证二甲双胍预防奥氮平引起精神分裂症患者的体质量增加和糖代谢紊乱的效果.方法 将37例未服过抗精神病药的精神分裂症患者,随机分为奥氮平(15 mg/d)联合二甲双胍组(750 ms/d;A组,18例)和奥氮平(15 mg/d)联合安慰剂组(B组,19例),治疗12周.于治疗前和治疗第4周末、8周末及12周末测定空腹血糖、胰岛素(INS)、身高、体质量、腰围、臀围,计算体质量指数(BMI)、腰臀比(WHR)、胰岛素抵抗指数(IRI)及治疗12周末体质量增加大于7%的比率.用阳性症状量表(SAPS)、阴性症状量表(SANS)于治疗前和治疗12周末评定疗效.结果 治疗12周末,A、B两组的体质量、BMI、WHR及B组患者的空腹INS和IRI较治疗前均升高(P＜0.05).治疗第8,12周末,B组的体质量、BMI、空腹INS和IRI的变化值高于A组(P＜0.05).B组体质量增加大于7%的比率(63%,12例)高于A组(17%,3例;P＜0.01).A、B两组的SAPS及SANS评分均显著低于治疗前(均P＜0.05),但组间差异均无统计学意义(P＞0.05).结论 二甲双胍能有效减轻奥氮平引起的体质量增加和糖代谢紊乱.     

阿立哌唑治疗奥氮平所致精神分裂症患者体质量增加的随机双盲对照研究

目的:探讨阿立哌唑干预奥氮平所致体质量增加的有效性及安全性。方法:将服用单一奥氮平治疗所致体质量增加≥7%的入组对象72例随机分为A组(加服阿立哌唑10 mg组,36例)及B安慰剂组(36例),入组时、治疗4周及8周分别测定体质量、体质量指数(BMI)、空腹血糖(FG)、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL)及高密度脂蛋白(HDL),并用阳性和阴性症状量表(PANSS)评定精神症状。结果:两组治疗前体质量、BMI、FG、TC、TG、LDL、HDL,差异无统计学意义(P0.05)。与治疗前比较,治疗8周,A组体质量、BMI、FG均明显下降(P0.05或P0.01),而HDL有明显增高(P0.05);B组体质量、BMI、FG均明显增高(P0.05或P0.01)。治疗4周体质量、BMI的变化值、治疗第8周体质量、BMI、FG、HDL的变化值,两组均差异有统计学意义(P0.05或P0.01)。结论:阿立哌唑能有效减轻奥氮平所致体质量增加和糖脂代谢紊乱。     

低能量膳食对奥氮平所致体质量增加的男性精神分裂症患者糖脂代谢的影响

目的:探讨低能量膳食对奥氮平所致体质量增加的男性精神分裂症患者糖脂代谢的影响。方法:选择2018年4月至2019年4月124例奥氮平所致体重增加的精神分裂症患者为研究对象,按照随机数字法分为A组(奥氮平片20 mg/d)、B组(奥氮平片20 mg/d联合二甲双胍片750 mg/d)和C组(奥氮平片20 mg/d联合低能量膳食)。比较3组患者治疗前和治疗3个月后体质量指数和糖脂代谢的变化。结果:治疗3个月后,A组体质量指数、空腹血糖、餐后2 h血糖、总胆固醇、三酰甘油、低密度脂蛋白胆固醇均高于B组和C组,高密度脂蛋白胆固醇低于B组和C组(P均0.05)。B组低密度脂蛋白胆固醇高于C组(P0.05),B组和C组在体质量指数、空腹血糖和餐后2 h血糖、总胆固醇、三酰甘油、高密度脂蛋白胆固醇方面差异无统计学意义(P均0.05)。结论:低能量膳食控制奥氮平所致体重增加的男性精神分裂症患者糖脂代谢水平的疗效与二甲双胍相当,提示膳食干预可作为该群体糖脂代谢异常的非药物性干预方案。     

盐酸小檗碱对奥氮平所致精神分裂症患者体质量增加的影响

目的:探讨盐酸小檗碱对奥氮平所致精神分裂症患者体质量增加的干预效果,以及与胰岛素抵抗的关系。方法:选取70例接受奥氮平单药治疗后出现体质量增加≥7%的精神分裂症患者,采用随机数字表法分为研究组35例(最终完成33例)和对照组35例(最终完成32例),在原奥氮平治疗基础上研究组合并盐酸小檗碱900 mg/d,对照组合并安慰剂900 mg/d,观察8周。分别在治疗前和治疗8周末测量两组体质量、体质量指数(BMI)、腰围(WC)、空腹血糖(FBG)、空腹胰岛素(Fins)水平及胰岛素抵抗指数(HOMA-IR);采用治疗中出现的症状量表(TESS)评估药物安全性。结果:以奥氮平使用剂量、使用时间为协变量的重复测量方差分析结果显示,体质量(F=4.569,F=78.784)、BMI(F=4.052,F=65.422)、WC(F=5.146,F=45.068)及HOMA-IR(F=9.171,F=21.342)的组间效应显著(P均0.05);体质量(F=78.784)、BMI(F=65.422)、WC(F=45.068)及HOMA-IR(F=21.342)的组间和治疗的交互效应显著(P均0.01);而时间效应不显著(P0.05)。研究组治疗前后体质量变化值及BMI变化值与HOMI-IR变化值呈正相关(r1=0.423,r2=0.403;P0.05);与WC变化值无明显相关(P0.05)。两组药物不良反应差异无统计学意义(P0.05)。结论:盐酸小檗碱可降低奥氮平所致精神分裂症患者的体质量增加,这可能与其改善胰岛素抵抗有关。     

奥氮平治疗首发精神分裂症的疗效分析

奥氮平为非典型抗精神病药物 ,其化学结构和药理作用机制与氯氮平均相似。有文献报道[1,2 ] ,奥氮平治疗精神分裂症有肯定的疗效。本文作者试用奥氮平治疗首发精神分裂症 ,以验证该药的疗效及安全性。现将结果报道于后。1　对象与方法1 1　对象　为 2 0 0 0年 9月～ 2 0 0 1年 10月在无锡市第七人民医院及无锡同仁医院门诊及住院的首发精神分裂症患者 ,均符合ＣＣＭＤ - 2 -Ｒ中精神分裂症诊断标准 ,无严重躯体疾病 ,共 2 5例。男 9例、女16例 ,年龄 18～ 4 5岁 ,平均 (2 5 7± 9 8)岁 ,病程 3～14个月 ,平均 (6 1± 4 6 )个月 ,偏…     

Metformin for treatment of clozapine-induced weight gain in adult patients with schizophrenia: a meta-analysis

Background

Long-term use of clozapine for individuals with schizophrenia carries a high risk for developing metabolic abnormalities, especially clozapine-induced weight gain. Previous studies suggest that metformin can decrease clozapine-induced weight gain, but the sample sizes of most of these studies are relatively small.

Methods

We identified randomized controlled trials (RCTs) published prior to December 15, 2015 about the use of metformin to treat clozapine-induced weight gain in adults with schizophrenia by searching several English-language and Chinese-language databases. Two independent researchers did the screening and data extraction. We used Revman 5.3 to conduct the meta-analyses, assessed the risk of bias (RoB), and assessed the strength of the evidence using the Cochrane Grades of Recommendation, Assessment, Development, and Evaluation (GRADE).

Results

Six studies with a pooled sample of 207 treatment-group patients and 207 control-group patients were included —— three double-blind, placebo-controlled RCTs and three RCTs that did not use placebo controls and were not blinded. The meta-analysis found that compared to the control condition, patients receiving metformin experienced significantly greater reductions in body weight (mean difference [MD]=-2.89 kg, 95% CI: -4.20 to -1.59 kg) and body mass index (BMI) (MD=-0.81, 95% CI: -1.16 to -0.45), but there was no significant difference between the groups in the prevalence of side effects. Based on the GRADE scale, the strength of the evidence for the change in weight outcome was ‘moderate’ and that for the change in BMI outcome was ‘high’, but the strength of evidence about differences in side effects between groups was ‘low’ or ‘very low’.

Conclusions

Adjunctive treatment with metformin appears to be effective for treating clozapine-induced weight gain and elevations in BMI in adult patients with schizophrenia. However, the quality of the evidence about the safety of this treatment is low, follow-up time in the available studies is relatively short, and half of the studies did not employ blinded assessment of outcome measures. Larger studies with placebo controls that follow patients for at least 24 weeks and that make blinded assessments of a range of relevant outcome measures (weight, BMI, blood lipids, insulin resistance, etc.) are needed to confirm these results.     

Long-term weight gain in patients treated with open-label olanzapine in combination with fluoxetine for major depressive disorder

OBJECTIVE: Patients with major depressive disorder (MDD) treated with olanzapine in combination with fluoxetine (OFC) demonstrate robust improvement in their depressive symptoms. Treatment with olanzapine may impact a patient's weight; thus, long-term weight gain and potential predictors (e.g., age and gender) and correlates (e.g., cholesterol and glucose levels) of weight gain were investigated in OFC-treated patients with MDD. METHOD: Outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnostic criteria for MDD were included (N = 549) in the current analyses of this 76-week, open-label study (February 2000 to July 2002). Maximum, endpoint, and potentially clinically significant (PCS; > or = 7% increase from baseline) weight gain; time to PCS weight gain; and predictors and correlates of weight change were assessed. Patients were treated once daily with oral olanzapine (6, 12, or 18 mg) plus fluoxetine (25, 50, or 75 mg) capsules. Statistical significance for all tests was based upon p < or = .05. RESULTS: Mean baseline-to-endpoint weight change was 5.6 +/- 6.6 kg (12.3 +/- 14.6 lb). Weight gain plateaued by 52 weeks. Fifty-six percent of patients met criteria for PCS weight gain by 76 weeks, and the median time to PCS weight gain was 16 weeks. Low baseline body mass index (BMI), female gender, younger age, and increased fluoxetine dose were predictors of weight gain; olanzapine dose was not. Patients with early (< or = 6 weeks) rapid PCS weight gain were 4.6 times more likely to gain substantial (> or = 15%) weight long-term (weeks 7-76). Changes to endpoint in total cholesterol and systolic blood pressure values were positively correlated with weight change. CONCLUSION: Long-term (76 weeks) OFC treatment may lead to a large percentage (56%) of patients meeting criteria for PCS weight gain (> or = 7%). The risk of weight gain may be significantly increased for OFC-treated patients who have a low BMI or who are female, younger, or taking high-dose fluoxetine. It is important that prescribers balance the risk of weight gain with the benefit of treatment for individual patients with depression.     

Topiramate mitigates weight gain in antipsychotic-treated patients with schizophrenia: meta-analysis of randomised controlled trials

Objective: Weight gain is one of the most challenging issues in patients with schizophrenia treated with antipsychotics. Several meta-analyses have been conducted to review the efficacy of topiramate in reducing weight, however, several issues regarding the methodology had arisen of which make the results remain ambiguous.

Methods: We conducted a meta-analysis of randomised controlled trials about the use of topiramate in patients with schizophrenia for weight reduction. Ten double-blinded randomised placebo-controlled trials and seven open-label randomised controlled trials included 905 patients.

Results: Patients treated with topiramate experienced a greater reduction in body weight and BMI. Patients in countries of the lower overweight population showed more significant BMI reduction. Besides, studies from the Middle East and South Asia showed the greatest effect in body weight change, followed by East Asia, then Europe/America. Topiramate group was outperformed control group with significant psychopathology improvement. No difference between two groups regarding the overall side effects.

Conclusions: Topiramate was significantly superior to control group in mitigating weight gain and psychopathology in antipsychotic-treated patients with schizophrenia. The effects of topiramate augmentation need further investigations in larger definitive studies using methodological rigor and thorough assessments.     

A psychoeducational program for weight loss in patients who have experienced weight gain during antipsychotic treatment with olanzapine

INTRODUCTION: The aim of this study was to evaluate the efficacy of a psychoeducational program (PEP) for weight control in patients who had experienced an increase of body weight during treatment with olanzapine. METHODS: Eligible patients were randomised to the PEP (Group 1) or to no intervention (Group 2) and continued on olanzapine. After 12 weeks, the PEP was also started in Group 2 and continued in Group 1, up to week 24. Body weight was measured every month. Other measures included quality of life, and change in plasma glucose and lipids levels. RESULTS: Patients in Group 1 (n=15) had a mean weight loss of 3.6 kg at week 12 and 4.5 kg at week 24 (p<0.01 at both times, p<0.01 between groups at week 12), while those in Group 2 (n=18) had no changes at week 12 and a significant weight loss at week 24 (-3.6 kg from week 12, p<0.01). Changes of BMI paralleled those of body weight. Quality of life (Q-LES-Q-SF categorisation) and functioning (GAF) significantly improved in the total population at endpoint (p<0.01). No significant changes were observed in fasting glucose and lipid profile, while insulin levels significantly decreased from baseline to endpoint in both groups (p<0.05). HOMA index and hepatic insulin sensitivity improved, too. DISCUSSION: Patients with increased BMI during treatment with olanzapine experienced significant weight and BMI loss following a structured psychoeducational program.     

Management of weight gain in patients with schizophrenia

Of the roughly 55% of the United States population that is considered overweight, half meet the criteria for obesity. Obesity is associated with serious health risks, but many clinicians graduate from medical school without a clear understanding of the effects of the foods that they and their patients consume. Obesity is more prevalent in people with mental illnesses, which poses an even greater challenge to clinicians. Antipsychotic treatment can cause weight gain, and mentally ill patients generally lack an understanding of nutrition as well as the ability to afford healthier foods. Therefore, clinicians must educate themselves about appropriate measures for preventing weight gain before or immediately after initiating antipsychotic therapy. Strategies for weight gain management that have proven effective in clinical trials include regular check-ups, lifestyle and medication counseling, medication assessments, behavioral control programs, and pharmacologic intervention. These approaches are necessary for clinicians to consider if efforts at reintegration of mentally ill patients are to succeed.     

Nocturnal hormone profiles in patients with schizophrenia treated with olanzapine

Nocturnal hormone profiles were measured in patients with schizophrenia with predominantly negative symptoms both under drug-free baseline conditions and after subchronic administration of the atypical antipsychotic olanzapine, with the aim of characterizing its pharmacological properties on the neuroendocrine level. The following hormones were studied in the sleep laboratory under polysomnographic control: adrenocorticotrophic hormone, cortisol, growth hormone (GH), prolactin, testosterone, and melatonin. Blood samples were taken at regular time intervals over the night, and serum concentrations of the hormones were determined. Ten patients completed the study, two of them were excluded from analysis due to incomplete hormone profiles. The dynamics of baseline nocturnal hormone secretion were similar to the patterns known from healthy subjects. After the treatment period of about 4 weeks, hypothalamic-pituitary-adrenal axis activity was reduced with decreased cortisol plasma levels compared to baseline conditions. Olanzapine induced a moderate prolactin elevation. The characteristic GH peak around sleep onset, clearly present under baseline conditions, was markedly reduced after treatment. Testosterone and melatonin secretion were not significantly altered. In conclusion, although interpretation is difficult in some cases due to interference with indirect effects of olanzapine administration and the consequences of the clinical course of the underlying schizophrenic disorder, the neuroendocrine findings are consistent with the receptor-binding profile of olanzapine where, beside the D(2) antagonism, the antiserotonergic properties are most important.     

Factors influencing acute weight change in patients with schizophrenia treated with olanzapine, haloperidol, or risperidone

OBJECTIVE: Clinical factors predicting weight change in patients with schizophrenia and related disorders during acute treatment with the antipsychotic drugs olanzapine, risperidone, and haloperidol were sought through retrospective analyses. METHOD: Six-week body-weight data from 2 trials, study 1 comparing olanzapine and haloperidol (N = 1,369) and study 2 olanzapine and risperidone (N = 268), were analyzed. Effects of 8 clinically relevant covariates--therapy, clinical outcome (Brief Psychiatric Rating Scale), baseline body mass index (BBMI), increased appetite, age, gender, race, and dose--on weight were compared. RESULTS: In study 1, olanzapine (vs. haloperidol) therapy, better clinical outcome, lower BBMI, and nonwhite race significantly affected weight gain. Effects of increased appetite and male gender on weight gain were significant for olanzapine but not for haloperidol. In study 2, better clinical outcome, lower BBMI, and younger age significantly affected weight gain. Increased appetite was more frequent during olanzapine treatment than during haloperidol, but not significantly different from risperidone. Significant differences in effect on weight change were found between olanzapine and haloperidol but not between olanzapine and risperidone. No evidence was found that lower antipsychotic drug doses were associated with lower weight gain. CONCLUSION: This report identifies predictive factors of acute weight change in patients with schizophrenia. Similar factors across antipsychotic drugs in predicting greater weight gain included better clinical outcome, low BBMI, and nonwhite race. Factors differing between conventional (haloperidol) and atypical (olanzapine) agents included increased appetite and gender. Choice of atypical antipsychotic drug (olanzapine vs. risperidone) was of minor importance with regard to influence on acute weight gain.