Metformin for olanzapine-induced weight gain: a systematic review and meta-analysis

Olanzapine is an atypical antipsychotic that is useful in schizophrenia and bipolar affective disorder, but its use is associated with troublesome weight gain and metabolic syndrome. A variety of pharmacological agents has been studied in the efforts to reverse weight gain induced by olanzapine, but current evidence is insufficient to support any particular pharmacological approach. We conducted a systematic review and meta-analysis of randomized controlled trials of metformin for the treatment of olanzapine-induced weight gain. Systematic review of the literature revealed 12 studies that had assessed metformin for antipsychotic-induced weight gain. Of these, four studies (n= 105) met the review inclusion criteria and were included in the final analysis. Meta-analysis was performed to see the effect size of the treatment on body weight, waist circumference and body-mass index (BMI). Weighted mean difference (WMD) for body weight was 5.02 (95% CI 3.93, 6.10) kg lower with metformin as compared with placebo at 12 weeks. For waist circumference, the test for heterogeneity was significant (P= 0.00002, I²= 85.1%). Therefore, a random effects model was used to calculate WMD, which was 1.42 (95% CI 0.29, 3.13) cm lower with metformin as compared with placebo at 12 weeks. For BMI, WMD was 1.82 (95% CI 1.44, 2.19) kg m⁻² lower with metformin as compared with placebo at 12 weeks. Existing data suggest that short term modest weight loss is possible with metformin in patients with olanzapine-induced weight gain.     

Predictors of antipsychotic-induced weight gain in first-episode psychosis: conclusions from a randomized, double-blind, controlled prospective study of olanzapine, risperidone, and haloperidol

BACKGROUND: Antipsychotic-induced weight gain is one of the most distressing adverse effects being observed in recent times. Most studies have been limited by several confounders. AIM: To evaluate the predictors of antipsychotic-induced weight gain in drug-naive patients with first-episode psychosis treated with olanzapine, risperidone, or haloperidol and compare them with a healthy matched control group. METHODS: Newly diagnosed patients with first-episode schizophrenia treated with antipsychotic medication-olanzapine, risperidone, or haloperidol-and matched healthy controls were followed for 6 weeks. Body mass index (BMI), waist circumference, and weight changes and proportions of subjects with more than 7% weight gain were calculated. The predictors of weight gain were explored. RESULTS: Ninety-nine patients with first-episode schizophrenia and 51 healthy controls were examined. Waist circumference (r = -0.25; P < 0.01) and weight (r = -0.24; P < 0.01) at baseline in addition to the disease process (P < 0.001) as well as antipsychotic use (P < 0.001) were associated with greater increases in weight and BMI. Olanzapine (77%) had greater clinically significant weight gain as compared with risperidone (63%) and haloperidol (22%). Lower BMI at baseline and a diagnosis of undifferentiated schizophrenia were associated with antipsychotic-induced weight gain. CONCLUSIONS: The results confirm clinically significant and substantial weight gain induced by antipsychotic treatment in drug-naive patients with first-episode schizophrenia and identify several risk factors for weight gain such as lower BMI scores, use of olanzapine, and a diagnosis of undifferentiated schizophrenia.     

Safety and tolerability of antipsychotic polypharmacy

INTRODUCTION: Antipsychotic polypharmacy (APP), the concomitant use of ≥ 2 antipsychotics, is common in clinical practice. Prior reviews have focused on the efficacy of APP, but no systematic review exists regarding the safety and tolerability of this practice. AREAS COVERED: A systematic review of adverse effects associated with APP was conducted to prepare this review; case series with ≥ 2 patients, chart reviews, naturalistic, database, cohort and randomized studies that reported on the association between APP in general or specific APP combinations and global or specific adverse effect were included. Methodological limitations of available studies are discussed and recommendations for clinicians and future research are provided. EXPERT OPINION: Across mostly small and uncontrolled studies, APP has been associated with increased global side effect burden, rates of Parkinsonian side effects, anticholinergic use, hyperprolactinemia, sexual dysfunction, hypersalivation, sedation/somnolence, cognitive impairment and diabetes. Effects on akathisia and mortality were inconclusive. Although some combinations, particularly aripiprazole augmentation of an agent with greater side effect burden, may reduce weight gain, dyslipidemia, hyperprolactinemia and sexual dysfunction, APP should remain a last-resort treatment option after monotherapy, switching and non-antipsychotic combinations have failed. More data are needed to further inform the individualized risk-benefit evaluation of APP.     

利培酮和氯氮平对精神分裂症患者血糖和脂代谢的影响

目的探讨长期使用利培酮和氯氮平对精神分裂症患者血糖和脂代谢的影响。方法收集2008年6月至2010年6月我院精神科门诊或住院首发精神分裂症患者70例,随机分为利培酮组和氯氮平组,每组35例。利培酮组采用利培酮治疗,氯氮平组采用氯氮平治疗。比较治疗前、治疗12个月后两组患者的BMI、腰围、臀围、腰臀比,FBS、TC、TG、HDL-c、LDL-c、TG/HDL-c、TC/HDL-c、ApoA1、ApoB,以及治疗12个月后糖尿病发生率。结果治疗12个月后两组患者BMI、腰围、臀围、腰臀比均较治疗前明显升高(P<0.05);但利培酮组BMI、腰围、腰臀比均明显低于氯氮平组,两组比较差异有统计学意义(P<0.05)。治疗12个月后,两组患者的FBS、TC、TG、HDL-c、LDL-c、TG/HDL-c、TC/HDL-c、ApoB均较治疗前明显升高,ApoA1较治疗前明显降低(P<0.05);但利培酮组的FBS、TC、TG、HDL-c、LDL-c、TG/HDL-c、TC/HDL-c、ApoB低于氯氮平组,ApoA1高于氯氮平组,两组比较差异有统计学意义(P<0.05);治疗12个月后,利培酮组糖尿病发生率明显低于氯氮平组(P<0.05)。结论氯氮平、利培酮均会对患者血糖、体重、脂代谢产生不良影响,而氯氮平的影响更明显,这种不良影响有可能会导致心脑血管并发症的发生和认知功能的损害。     

Antipsychotic-induced weight gain in chronic and first-episode psychotic disorders: a systematic critical reappraisal

Antipsychotic-induced weight gain is an important issue in the treatment of psychotic illnesses, and affects 80% of individuals being treated with antipsychotic drugs. However, the true dimension of weight gain and many accepted 'facts' in this area remain unclear as most research has been conducted in short-term trials and has included individuals receiving prolonged antipsychotic treatment.This review aims to systematically and critically review the evidence on weight gain induced by the two leading second-generation antipsychotics (olanzapine and risperidone) and the most widely researched first-generation antipsychotic (haloperidol) in patients with chronic and first-episode psychotic disorders.Weight gain was 3- to 4-fold greater in studies that included young patients with limited previous exposure to antipsychotic agents in both short-term studies (7.1-9.2 kg for olanzapine, 4.0-5.6 kg for risperidone and 2.6-3.8 kg for haloperidol vs 1.8-5.4 kg, 1.0-2.3 kg and 0.01-1.4 kg, respectively, in studies that included patients with chronic psychotic disorders) and long-term trials (10.2-15.4 kg for olanzapine, 6.6-8.9 kg for risperidone and 4.0-9.7 kg for haloperidol vs 2.0-6.2 kg, 0.4-3.9 kg and -0.7 to 0.4 kg, respectively). The same disparity was observed regarding the proportion of patients increasing their baseline weight by > or =7% (the cut-off for clinically significant weight gain).Recent studies carried out in young patients with first-episode psychosis (FEP), along with methodological artefacts in studies of chronic populations, suggest that the magnitude of weight gain reported by much of the literature could in fact be an underestimation of the true magnitude of this adverse effect. Although antipsychotics present idiosyncratic patterns of weight gain, they may also generate similar absolute gains.     

Obesity and weight gain as risk factors for erosive oesophagitis in men

Background  Although obesity and weight gain increase the risk for symptoms of gastro-oesophageal reflux disease, their association with erosive oesophagitis is still unclear in the male population.
Aim  To evaluate, in men, the association of body mass index (BMI) and weight gain with endoscopically proven erosive oesophagitis.
Methods  A total of 8571 Korean men in a comprehensive screening cohort were enrolled. Effects of BMI and abdominal obesity on erosive oesophagitis were estimated with odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression analysis. We also evaluated the association between erosive oesophagitis and BMI change after 1–3 years.
Results  The prevalence of erosive oesophagitis was 6.4% (552/8571). In univariate analysis, the ORs for erosive oesophagitis increased as BMI or waist circumference increased ( P for trend <0.001, both). In multivariate analysis, OR for erosive oesophagitis increased as BMI increased ( P for trend = 0.002), while the significance of waist circumference was attenuated ( P for trend = 0.13). Increase in BMI (≥1 kg/m²) was associated with persistence of erosive oesophagitis (OR = 2.83, 95% CI: 1.01–7.92, P  = 0.04) and new development of the disease (OR = 2.13, 95% CI: 1.38–3.28, P  = 0.001) compared with BMI change less than 1 kg/m².
Conclusions  Elevated BMI and weight gain have a significant association with erosive oesophagitis.     

Adiposity and insulin sensitivity derived from intravenous glucose tolerance tests in antipsychotic-treated patients.

Cardiovascular disease is more common in schizophrenia patients than in the general population, with a hypothesized contribution from increases in adiposity produced by antipsychotic medications. We sought to test the relationship between adiposity and insulin resistance using frequently sampled intravenous glucose tolerance tests (FSIVGTTs) to quantify whole-body insulin sensitivity in chronically treated patients with schizophrenia or schizoaffective disorder and untreated healthy controls. FSIVGTTs, body mass index (BMI), and waist circumference were obtained in nondiabetic patients (n=63) receiving olanzapine, risperidone, ziprasidone, or first generation antipsychotics, as well as in healthy controls (n=14). Subject groups (including untreated healthy controls) were matched for BMI and all treated patient groups were additionally matched for age. Bergman's minimal model (MinMod) was used to calculate insulin sensitivity (S(I)), as well as secondary measures of interest. BMI and waist circumference significantly predicted insulin sensitivity measured as MinMod S(I) (F(1,62)=35.11, p<0.0001 and F(1,46)=24.48, p<0.0001, respectively). In addition, BMI and waist circumference significantly predicted the acute plasma insulin response to the glucose challenge (AIR(G)), consistent with a beta cell compensatory response to insulin resistance (MinMod AIR(G) F(1,65)=22.42, p<0.0001 and F(1,49)=11.72, p=0.0013, respectively). Adiposity levels occurring during antipsychotic treatment are strongly related to insulin resistance, confirming that antipsychotic-induced weight gain can contribute to increased cardiometabolic risk in this population.     

非典型性抗精神病药引起体重增加的Meta分析

目的:评价非典型抗精神病药所致的体重增加不良反应.方法:根据关键词检索出1993～2009年的文献,根据入选排除标准入选合格文献进行Meta分析.结果:以体重增加≥7%以RR作为效应指标进行系统评价,与对照组相比较,不同试验药物发生体重增加的风险不同,布南色林最低,奥氮平最高.奥氮平、喹硫平、利培酮、阿立哌唑、伊潘立酮...     

Systematic review of pharmacotherapy of disruptive behavior disorders in children and adolescents

RATIONALE: Pharmacotherapy is frequently considered in the treatment of disruptive behavior disorders (DBDs) in children and adolescents. There are, however, no systematic reviews of this literature. OBJECTIVES: The aim of this work is to determine whether medication is effective in treating pediatric disruptive behavior disorders and related problems of impulse control, as well as to examine differences in the treatment response and tolerability of different medication classes and agents. MATERIALS AND METHODS: Randomized controlled trials of the pharmacotherapy of DBDs in children and adolescents were reviewed, and a meta-analysis of 14 trials (823 participants) was conducted. RESULTS: There is some evidence of the effectiveness of medication in treating DBDs, with positive outcomes for lithium and risperidone in particular. Pharmacotherapy also demonstrated some efficacy in reducing symptoms of aggression. Medication was relatively well-tolerated, as indicated by equivalent dropout rates in medication and comparison groups. CONCLUSIONS: There are relatively few controlled trials of the pharmacotherapy of disruptive behavior disorders or other impulse control disorders, despite the importance of research in this area. Given the potential adverse effects of agents such as lithium and risperidone, a careful risk-benefit analysis is needed for each patient.     

帕利哌酮缓释片与利培酮片对女性首发精神分裂症患者糖脂代谢影响的对比研究

目的 观察对比帕利哌酮缓释片与利培酮片对女性首发精神分裂症患者糖脂代谢影响。方法 将85例在德阳市精神卫生中心治疗的女性首发精神分裂症患者随机分为观察组42例和对照组43例，分别给予帕利哌酮缓释片和利培酮片单药治疗2个月。治疗前后测量体质量指数（BMI）、腰围、三酰甘油（TG）、总胆固醇（TC）、高密度脂蛋白（HDLC）、低密度脂蛋白（LDLC）、空腹血糖（FPG）、餐后2 h血糖（2 h PG），采用阳性和阴性症状量表（PANSS）进行疗效评价。结果 治疗前两组PANSS总分及各因子分（阳性症状、阴性症状和精神病性分）及治疗后两组PANSS总分及各因子分分别比较，差异均无统计学意义。与治疗前相比，治疗后两组PANSS总分[观察组（47.94±13.64）分，对照组（49.07±12.56）分]及各因子分均显著低于治疗前PANSS总分[观察组（86.31±9.21）分，对照组（85.95±9.77）分]及各因子分，差异具有统计学意义（P<0.05）。治疗前两组患者糖、脂各指标比较，差异无统计学意义。治疗后对照组TG、TC、LDLC、BMI和腰围上升，HDLC降低，与治疗前比较，差异具有统计学意义（P<0.05）；观察组BMI和腰围与治疗前比较明显变大，差异具有统计学意义（P<0.05）。观察组治疗后TG、TC、LDLC、BMI和腰围均显著低于对照组，HDLC显著高于对照组，差异具有统计学意义（P<0.05）。两组FPG、2hPG、SBP和DBP比较，差异无统计学意义。观察组患者不良反应发生率明显低于对照组（P<0.05）。结论 帕利哌酮缓释片和利培酮对女性首发精神分裂症患者具有相同的疗效，但是帕利哌酮缓释片对女性患者血脂、BMI和腰围的影响较小，要优于利培酮片。     

Risperidone: new indication. Behavioural disorders in children with autism or mental disabilities: no progress

(1) Sedative drugs are one option when autistic or mentally disabled children have behavioural disorders that place them (or other people) in physical danger. Among the classic neuroleptics, haloperidol is the drug with the best-documented efficacy and safety. Placebo-controlled trials have also shown lithium to be effective for this use. (2) Clinical evaluation of risperidone in children with mental disabilities includes 3 placebo-controlled double-blind trials, 2 of which involved 118 and 110 children aged from 5 to 12 years who were treated for 6 weeks. All 3 trials showed a partial behavioural improvement in about 75% of children receiving risperidone, versus about 30% of children in the placebo groups. (3) Clinical evaluation of risperidone in autistic children includes 2 placebo-controlled double-blind trials involving 110 and 79 children who were treated for 8 weeks. One of these studies has been published in detail: 69% of children partially improved with risperidone, versus 12% of the children on placebo. (4) Given the absence of clinical trials comparing risperidone with haloperidol or lithium, there is no evidence that risperidone is more effective than these other treatments. (5) The principal adverse events observed in short-term trials of risperidone were drowsiness (affecting about 50% of children), weight gain (about 1.2 kg per month during the first months of treatment), and hyperprolactinaemia (affecting about 12% of children). Extrapyramidal disorders were infrequent during short-term trials, but their incidence reached about 25% after a year of risperidone treatment. (6) The impact of long-term risperidone therapy on growth and mental development is not known. (7) In France treatment is about 7 times more expensive with risperidone than with haloperidol. (8) In practice, the risk-benefit balance of risperidone in the treatment of autistic or mentally disabled children with behavioural disorders is no better overall than that of older products such as haloperidol and lithium, which, in the absence of anything better, remain the standard drugs.     

A comparison of risperidone-induced weight gain across the age span

A systematic and comprehensive literature search was performed to determine the extent of weight gain induced by risperidone (RIS) treatment across the age span. The review and pooled data analyses were based on double-blind, open trial, and case series studies containing findings on drug dose, age of subjects, weight gain, duration of treatment, and if available, baseline body weight, body mass index, and the percent of subjects experiencing a prominent RIS-induced weight gain. Drug-induced weight gain per month for youths was defined as recorded weight gain minus the age-expected weight gain. The major findings from pooled data were (1) preadolescent youths received a smaller average daily dose and lower mg/kg/d dose of RIS than adolescents, and adolescents in turn had lower mg/kg/d doses than middle-aged adults; (2) RIS-induced weight gain as a percentage of baseline body weight was most pronounced in the preadolescent years and decreased with advancing age; (3) adults over age 65 experienced little to no RIS-induced weight gain; and (4) RIS treatment led to consistently greater body mass index percentage increases for youths than for adults. Available data thus suggest that across the age span, youths are the most sensitive to weight gain induced by a commonly prescribed second-generation neuroleptic.     

Antipsychotic-induced weight gain and therapeutic response: a differential association

This study investigated the association between antipsychotic-induced weight gain and therapeutic response to haloperidol and three commonly used atypical neuroleptic medications in schizophrenia and schizoaffective disorder. The subjects were 151 patients enrolled in a double-blind experiment with a duration of 14 weeks comparing the therapeutic efficacy of haloperidol (n = 36), clozapine (n = 38), olanzapine (n = 38), and risperidone (n = 39). Absolute and relative (%) gain in body weight and body mass index (BMI) was determined for the entire duration of the double-blind treatment period; therapeutic response was assessed by the total score and the individual subscales of the Positive and Negative Symptom Scale. Compared with the pretreatment baseline, results indicated that for olanzapine and clozapine, therapeutic response was closely related to an absolute and relative gain in weight and to a gain in BMI. No association between weight gain and therapeutic response was found for risperidone and haloperidol. These findings suggest that patients who are likely to have the maximal benefits of olanzapine or clozapine treatment for symptom alleviation are at the highest risk of a clinically significant increase in weight gain.     

Elderly dementia patients and neuroleptics: excess mortality

In 2005, a meta-analysis conducted by the US Food and Drug Administration showed a 1% to 2% increase in mortality, in absolute values, in elderly dementia patients treated with so-called atypical neuroleptics than in patients not receiving neuroleptics. One placebo-controlled trial, two new meta-analyses, and several cohort studies of various sizes and designs have been published since 2005. The double-blind placebo-controlled trial showed a statistically significant decline in mortality when neuroleptic therapy (risperidone or haloperidol in most cases) was withdrawn. One of the meta-analyses showed excess mortality in patients receiving atypical neuroleptics compared with those not receiving neuroleptics. The other meta-analysis, focusing solely on risperidone, showed a higher risk of vascular death than in placebo-treated patients. Four very large cohort studies also showed a trend towards excess mortality with conventional neuroleptics. In practice, as all neuroleptics have negative risk-benefit balances in elderly dementia patients, it is best to avoid using them in these patients, if possible. If a neuroleptic is nonetheless prescribed, treatment should be for the shortest possible duration, at the minimum effective dose.     

Efficacy,acceptability and tolerability of antipsychotics in patients with schizophrenia and comorbid substance use. A systematic review and meta-analysis

Patients with schizophrenia and substance related comorbidity or substance induced psychotic disorder are difficult to treat. Although the prevalence of a comorbid substance use is approximately 40% in schizophrenia, such patients are usually excluded from clinical trials. We therefore performed a random-effects meta-analysis of all randomized controlled antipsychotic drug trials in this patient subgroup. We searched multiple databases up to May, 2018. The primary outcome was the reduction of substance user; secondary outcomes were craving, mean reduction of substance use, overall change in schizophrenia symptoms, positive and negative symptoms, response, dropouts, quality of life, social functioning, weight gain, sedation, prolactin, extrapyramidal side effects and use of antiparkinsonian medication. We identified 27 references from 19 RCTs published from 1999 to March 2017 including 1742 participants. The most frequent types of substance abuse were cannabis (8 studies) and cocaine (6 studies) use/dependence. Clozapine was superior to other antipsychotics for reduction of substance use and risperidone to olanzapine for craving. Olanzapine, clozapine and risperidone showed superiority for symptom reduction compared to some other drugs. When reported, results of side-effects followed known patterns. The evidence-base is considerable (19 RCTs), however, firm conclusions cannot be drawn due to small sample sizes of individual studies and insufficient reporting.     

Second-generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review

Increasing numbers of reports concerning diabetes, ketoacidosis, hyperglycaemia and lipid dysregulation in patients treated with second-generation (or atypical) antipsychotics have raised concerns about a possible association between these metabolic effects and treatment with these medications. This comprehensive literature review considers the evidence for and against an association between glucose or lipid dysregulation and eight separate second-generation antipsychotics currently available in the US and/or Europe, specifically clozapine, olanzapine, risperidone, quetiapine, zotepine, amisulpride, ziprasidone and aripiprazole. This review also includes an assessment of the potential contributory role of treatment-induced weight gain in conferring risk for hyperglycaemia and dyslipidaemia during treatment with different antipsychotic medications. Substantial evidence from a variety of human populations, including some recent confirmatory evidence in treated psychiatric patients, indicates that increased adiposity is associated with a variety of adverse physiological effects, including decreases in insulin sensitivity and changes in plasma glucose and lipid levels. Comparison of mean weight changes and relative percentages of patients experiencing specific levels of weight increase from controlled, randomised clinical trials indicates that weight gain liability varies significantly across the different second generation antipsychotic agents. Clozapine and olanzapine treatment are associated with the greatest risk of clinically significant weight gain, with other agents producing relatively lower levels of risk. Risperidone, quetiapine, amisulpride and zotepine generally show low to moderate levels of mean weight gain and a modest risk of clinically significant increases in weight. Ziprasidone and aripiprazole treatment are generally associated with minimal mean weight gain and the lowest risk of more significant increases. Published studies including uncontrolled observations, large retrospective database analyses and controlled experimental studies, including randomised clinical trials, indicate that the different second-generation antipsychotics are associated with differing effects on glucose and lipid metabolism. These studies offer generally consistent evidence that clozapine and olanzapine treatment are associated with an increased risk of diabetes mellitus and dyslipidaemia. Inconsistent results, and a generally smaller effect in studies where an effect is reported, suggest limited if any increased risk for treatment-induced diabetes mellitus and dyslipidaemia during risperidone treatment, despite a comparable volume of published data. A similarly smaller and inconsistent signal suggests limited if any increased risk of diabetes or dyslipidaemia during quetiapine treatment, but this is based on less published data than is available for risperidone. The absence of retrospective database studies, and little or no relevant published data from clinical trials, makes it difficult to draw conclusions concerning risk for zotepine or amisulpride, although amisulpride appears to have less risk of treatment-emergent dyslipidaemia in comparison to olanzapine. With increasing data from clinical trials but little or no currently published data from large retrospective database analyses, there is no evidence at this time to suggest that ziprasidone and aripiprazole treatment are associated with an increase in risk for diabetes, dyslipidaemia or other adverse effects on glucose or lipid metabolism. In general, the rank order of risk observed for the second-generation antipsychotic medications suggests that the differing weight gain liability of atypical agents contributes to the differing relative risk of insulin resistance, dyslipidaemia and hyperglycaemia. This would be consistent with effects observed in nonpsychiatric samples, where risk for adverse metabolic changes tends to increase with increasing adiposity. From this perspective, a possible increase in risk would be predicted to occur in association with any treatment that produces increases in weight and adiposity. However, case reports tentatively suggest that substantial weight gain or obesity may not be a factor in up to one-quarter of cases of new-onset diabetes that occur during treatment. Pending further testing from preclinical and clinical studies, limited controlled studies support the hypothesis that clozapine and olanzapine may have a direct effect on glucose regulation independent of adiposity. The results of studies in this area are relevant to primary and secondary prevention efforts that aim to address the multiple factors that contribute to increased prevalence of type 2 diabetes mellitus and cardiovascular disease in populations that are often treated with second-generation antipsychotic medications.     

奥氮平与奋乃静对老年精神分裂症患者的体重、血糖及血脂影响的对照研究

目的 探讨奥氮平与奋乃静对老年精神分裂症患者的体重、血糖及血脂等的影响.方法 对68例住院的老年精神分裂症患者,随机分成奥氮平与奋乃静治疗组,在12周的治疗的不同时期观察体重、体重指数、腹围、血糖及血脂的变化,同时对两组之间进行以上数据的比较研究.结果 奥氮平与奋乃静组都会引起相应的体重、体重指数和腹围及部分血脂值的增加,而奥氮平组的体重及体重指数增加更加明显,奥氮平与奋乃静在对老年精神分裂症患者的腹围、血糖、血脂等方面的影响没有明显的区别.结论 非经典抗精神病药物奥氮平与经典抗精神病药物奋乃静都会引起老年精神分裂症患者部分代谢指标的变化,非经典药物对体重等的影响要引起重视.     

Perceptions of weight gain and bipolar pharmacotherapy: results of a 2005 survey of physicians in clinical practice

ABSTRACT

Objective: To assess the perceptions of clinicians in the psychiatric community about pharmacotherapy and its impact on weight gain and adverse metabolic effects in patients with bipolar disorder.

Methods: In November 2005, self-administered questionnaires were sent to 7000 psychiatrists who treat bipolar disorder in their clinical practice. An additional mailing of these questionnaires was sent in January 2006 to a different group of 7000 psychiatrists who treat bipolar disorder in their clinical practice. The first 298 completed surveys were analyzed.

Results: Almost half of the respondents (48%) were psychiatrists in individual private practice and 32% were in community mental health centers. About two-thirds of respondents reported that 30–60% of their bipolar patients were overweight. Thirty-eight percent of respondents reported metabolic syndrome present in 20–40% of their patients. Almost all respondents (96%) reported a 20?lb increase in patients’ weight as a troublesome potential adverse event associated with the use of some agents. After initiating a new medication, more than 80% of respondents monitored their patients’ weight, fasting plasma glucose level, and fasting lipid profile at regular intervals. However, 80% did not monitor waist circumference. Overall, respondents viewed several agents (aripiprazole, ziprasidone, carbamazepine, and lamotrigine) as not (or minimally) problematic in terms of weight gain and adverse metabolic concerns. Clozapine and olanzapine were viewed as highly problematic due to their propensity to induce weight gain and negatively influence lipid and glucose metabolism. Other agents considered to be minimally to moderately problematic in terms of weight gain and metabolic issues were quetiapine, risperidone, lithium, and valproate. Respondents reported that the profile of a bipolar agent in terms of weight gain and adverse metabolic effects was an important consideration in the management of bipolar disorder.

Conclusion: Although the study is limited by a low response rate and self-selection of respondents, clinicians who did respond were concerned about the risks of weight gain and metabolic disturbances in their patients treated with bipolar agents. For most parameters, such concerns were being integrated into clinical care. However, it appears that there is a need to increase clinicians’ appreciation of the importance of abdominal obesity and the need to monitor waist circumference. A growing recognition of the differences in weight-gain potential and adverse metabolic effects among agents appears to have had a definite impact on prescribing patterns in the management of bipolar disorder.     

Metabolic syndrome in female patients with schizophrenia treated with second generation antipsychotics: a 3-month follow-up

The objective of this study was to determine the occurrence of metabolic abnormalities among previously unmedicated female patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition schizophrenia spectrum disorders and their associations with olanzapine and risperidone treatment. We analysed 94 female patients who were treated with olanzapine or risperidone in the period of 3 months. Analysed variables included fasting glucose, total cholesterol, low-density lipoprotein (LDL), high-density lipoproteins and triglycerides in blood, blood pressure (BP), waist and hip circumferences and body mass index (BMI). At baseline, 14 patients (15%) fulfilled criteria for metabolic syndrome. After 3 months of treatment, 25 patients (27%) fulfilled criteria for metabolic syndrome, and their baseline BMI was the only predictor for its development. Treatment with both antipsychotics was associated with significant increase in waist circumference. Positive family history of diabetes mellitus contributed to a significant greater increase in abdominal obesity, significant higher baseline levels and a borderline significant increase in fasting glucose among olanzapine-treated patients. Olanzapine admission was associated with a significant increase in LDL and risperidone with a significant increase in triglycerides. Metabolic abnormalities seem to be more prevalent in unmedicated female patients with schizophrenia spectrum disorders than expected based on results in general population (adjusted for age and sex). Olanzapine treatment might induce significant alterations in metabolic profiles, especially among patients with positive family history of diabetes, mostly by inducing abdominal obesity. The association of risperidone application and increase in triglyceride level still needs to be determined.     

第二代抗精神病药物治疗对精神疾病儿童体质量及代谢的影响

目的 探讨利培酮或喹硫平长期治疗儿童精神疾病后,对肥胖及相关代谢失调的影响.方法 选取年龄2～18岁的具有精神类疾病的患者130例作为研究对象,所有患者治疗前均未服用过第二代抗精神药物(SGA),采用自然年度纵向调查法,研究分析了患儿的身体质量指标、生化指标、代谢参数.在12个月的研究周期内,共46例患儿(利培酮组25例,喹硫平组21例)的资料用于分析.结果 SGA治疗12个月后,患儿的体质量显著增加,利培酮组平均增加10.6(7.8～13.6)kg,喹硫平组平均增加9.5(6.3～12.7)kg,两组比较差异有统计学意义(P<0.05).同时,两组患儿的体质量指数Z(BMI z)评分也显著增高,儿童患超重或者肥胖的发生率也显著增加.快速血糖平均水平及高密度脂蛋白与总胆固醇比值明显增高,增高量分别为0.24(0.04-0.43)mmol·L-1和0.49(0.16～0.81)mmol·L-1.结论 儿童抗精神药物治疗12个月期间,儿童腰围显著增加、血脂指标异常,故儿童肥胖及代谢失调的风险显著升高.这一研究结果,对早期发现及代谢副作用治疗的有序检测具有重要意义.