Effects of patient demographics,risperidone dosage,and clinical outcome on body weight in acutely exacerbated schizophrenia

BACKGROUND: Predictors for risperidone-related weight gain remain unclear. This study aimed to identify clinical factors influencing body weight in risperidone-treated patients. METHOD: One hundred forty-six newly hospitalized DSM-IV schizophrenia patients with acute exacerbation entered this prospective, 6-week, repeated-measures trial. The mean +/- SD risperidone dose was 4.3 +/- 1.4 mg/day at week 6. Efficacy, body weight, and tolerability were measured biweekly. Efficacy was assessed with the Positive and Negative Syndrome Scale (PANSS) and the Nurses' Observation Scale for Inpatient Evaluation (NOSIE). For determining the impacts of possible prognostic factors on body weight, we utilized generalized estimating equation methods to control for other variables and the within-subject dependence over repeated assessments. RESULTS: After the effects of other factors (including baseline body weight) were adjusted, every 1-week increase in treatment duration raised body weight by 0.442 kg (p <.0001). Increasing baseline body weight by 1 kg reduced weight gain by 0.022 kg (p <.0001). Every 1-year increment in age decreased body weight by 0.052 kg (p <.001). Undifferentiated subtype predicted higher weight by around 0.9 kg than other sub-types (p <.05). Each 1-mg/day increment in risperidone dosage heightened body weight by 0.084 kg (p =.015). Responders (those with PANSS total-score reduction > or = 20%) also had higher weight by 0.513 kg on average (p =.007). Specifically, every 1-point diminution in score in PANSS total, PANSS positive, PANSS negative, PANSS cognitive, and NOSIE increased body weight, on average, by 0.029 kg, 0.057 kg, 0.079 kg, 0.079 kg, and 0.035 kg, respectively (p < or =.009). Other variables did not have significant influences. CONCLUSION: The results suggest that lower initial body weight, younger age, undifferentiated subtype, higher dosage, and treatment response (for positive, negative, and cognitive symptoms and social functioning) are associated with greater weight gain in acutely ill patients treated with risperidone. Further studies with longer observation and in other populations are needed.     

氯氮平所致体重增加与精神症状的相关性研究

探讨氯氮平治疗精神分裂症时体重增加与精神症状的相关性。　　方法　我们对 2 2例首次发病的精神分裂症在氯氮平治疗 1 2周内观察体重与精神症状变化情况。　　结果　发现1 3例 ( 1 3 / 2 2 )患者体重增加程度大于 5% ;在氯氮平治疗期间 ,从第 4周末开始体重增加明显 ;体重增加程度与精神症状及阴性症状改善有非常明显正相关 (r =0 .74,P <0 0 1 ) ,与阳性症状改善有明显正相关 (r=0 44 ,P <0 0 5) ;8例体重显著增加者与其他 1 4例病人比较 ,前者的精神症状改善明显优越于后者 (P <0 0 1 )。　　结论　氯氮平引起体重增加除与氯氮平的药理学作用有关外 ,还与精神症状的改善有相关性     

Mycophenolate mofetil in the therapy of polymyositis associated with a polyautoimmune syndrome

Mycophenolate mofetil 1.5 g daily (30 mg/kg body weight) was given to a patient with ankylosing spondylitis, ulcerative colitis, and severe refractory polymyositis after conventional treatment regimes had failed. No severe side effects occurred. Considerable improvement of clinical symptoms and electromyographic findings were seen within 6 months after the initiation of mycophenolate mofetil, allowing for tapering and discontinuation of methylprednisolone. Mycophenolate mofetil may be considered as an useful alternative in the treatment of polymyositis when standard therapeutic regimens fail.     

氯氮平和利培酮对精神分裂症患者体质量的影响

目的:探讨氯氮平和利培酮对精神分裂症患者体质量(体重)的影响及相关因素。方法:选择符合国际疾病分类第10版(ICD-10)精神分裂症的诊断标准,空腹血糖正常,无严重躯体疾病,1周内未用任何抗精神病药的住院患者,共计65例,其中利培酮组32例,氯氮平组33例。两组患者于治疗前和治疗6周末分别做葡萄糖耐量试验,测空腹血胰岛素,测量体质量、身高,计算体质量指数(BMI),评定阳性与阴性症状量表(PANSS)。结果:①治疗后体质量增加者氯氮平组24例(占72.7%),利培酮组19例(占59.4%);氯氮平组体质量平均增加2.5kg,利培酮组1.4kg;②氯氮平组体质量增加与进食量增加、胰岛素水平增加和PANSS评分减分率相关(P<0·05),体质量增加者餐后1h血糖升高;③利培酮组体质量增加与年龄、病程显著相关(P<0·05),与基础BMI存在负相关倾向;④两组治疗后均出现糖耐量减低(IGT)和暂时诊断糖尿病(DM)。结论:氯氮平和利培酮均能导致体质量增加,体质量增加更易对糖代谢造成不良影响。     

Changes in weight during a 1-year trial of fluoxetine.

OBJECTIVE: Fluoxetine has been associated with weight loss during acute treatment, but no controlled studies of weight change during long-term treatment with fluoxetine or other selective serotonin reuptake inhibitors have been reported. Weights were assessed for patients whose depressive symptoms had disappeared with acute fluoxetine treatment. Patients were then randomly assigned to continuation treatment with fluoxetine or placebo. METHOD: Patients whose illness had remitted after 12 weeks of treatment with fluoxetine, 20 mg/day, were randomly assigned to receive up to 38 weeks of treatment with fluoxetine or placebo. Weight was assessed at each visit. Change in weight was analyzed during the initial 12 weeks of acute treatment and after 14, 26, and 38 weeks. Relationships between weight change and body mass index and between weight change and appetite change were assessed. RESULTS: During the initial 4 weeks of therapy, a mean absolute weight decrease of 0.4 kg was observed for all patients. Among patients who completed 50 weeks of therapy, the mean absolute weight increase during continuation treatment was similar for both the placebo- and fluoxetine-treated groups. Weight increase was not related to initial body mass index but was related to both poor appetite at study entry and to improvement in appetite after recovery. No patients discontinued therapy because of weight gain. CONCLUSIONS: Acute therapy with fluoxetine is associated with modest weight loss. After remission of depressive symptoms, weight gain for patients taking fluoxetine for longer periods is not different from that for patients taking placebo and is most likely related to recovery from depression.     

The functional role of exercise in the development of weight and diet concerns in women

The functional role of exercise in the development of weight preoccupation and body dissatisfaction was examined. One hundred and twelve females, identified as regular participants in exercise programmes, completed an inventory that provided information on attitudes, behaviours and psychological characteristics related to dieting and weight-control, as well as a self-report of physical activity. A structural equation model was tested that provides support for the notion that Body Mass Index, emotional reactivity and physical activity have statistically significant direct effects on weight and diet concerns, but that weight and diet concerns do not predict the degree of participation in physical activity. Significant differences in eating disorder indicators were found between sub-groups identified as 'constantly dieting' and 'rarely dieting'. The tentative, but important, conclusion was drawn that regular participation in a fitness programme may be causally related to excessive concern with weight and dieting.     

Creatine therapy in myophosphorylase deficiency (McArdle disease): a placebo-controlled crossover trial

OBJECTIVE: To determine whether treatment with creatine can improve exercise intolerance in myophosphorylase deficiency (McArdle disease). DESIGN: Double-blind, placebo-controlled crossover study with oral creatine monohydrate supplementation. PATIENTS: Nine patients with biochemically and genetically proven McArdle disease were treated. INTERVENTION: Five days of daily high-dose creatine intake (150 mg/kg body weight) were followed by daily low-dose creatine intake (60 mg/kg). Each treatment phase with creatine or placebo lasted 5 weeks. MAIN OUTCOME MEASURES: The effect of treatment was estimated at the end of each treatment phase by recording clinical scores, ergometer exercise test results, phosphorus 31 nuclear magnetic resonance spectroscopy, and surface electromyography. RESULTS: Of 9 patients, 5 reported improvement of muscle complaints with creatine. Force-time integrals (P =.03) and depletion of phosphocreatine (P =.04) increased significantly during ischemic exercise with creatine. Phosphocreatine depletion also increased significantly during aerobic exercise (P =.006). The decrease of median frequency in surface electromyograms during contraction was significantly larger (P =.03) with creatine. CONCLUSION: This is the first controlled study indicating that creatine supplementation improves skeletal muscle function in McArdle disease.     

Adrenal Cushing's syndrome may resemble eating disorders

We encountered a patient who presented extreme weight loss and received an eating disorder diagnosis that was later identified as adrenal Cushing's syndrome. A 32-year-old woman with a 2-year history of an eating disorder was admitted to our psychiatric ward due to dehydration, malnutrition and low weight. Her height and body weight were 152.1 cm and 29.8 kg, respectively (body mass index: 12.8). Her other symptoms included a depressed mood, decreased interest, retardation and suicidal ideation. Standard medical cares were prescribed to treat the depressive symptoms and eating disorder, but the depressive episode and low body weight of the patient persisted. Computed tomography of the abdomen revealed an unexpected left adrenal gland tumor. Cushing's syndrome was diagnosed based on several endocrinological examinations. After an enucleation of the left adrenal gland tumor, the patient began eating, and her body weight increased gradually. Her body weight increased to 42.0–47.0 kg (body mass index: 18.2–20.3). Her mental and physical conditions had stabilized. This case suggests that adrenal Cushing's syndrome may resemble eating disorders.     

Healthy behavior change of adults with mental retardation: attendance in a health promotion program

Participation in a health promotion program for 192 overweight and obese adults with mental retardation was associated with behavior change resulting in reduction of body mass index-BMI (weight in kg, divided by height in meters, squared) by the end of the program. We analyzed the mediating and intermediate factors contributing to weight reduction and found knowledge and exercise to be the primary contributing factors. The curriculum emphasized exercise, nutritional choices, and stress reduction. Participation in the program was associated with a reduction of 0.8 BMI or approximately 2.3 kg for 26% of the participants. Increased knowledge about healthy diet and exercise was the most significant mediator of program impact on BMI.     

Wellness intervention for patients with serious and persistent mental illness

INTRODUCTION: Weight gain and obesity that emerge during psychopharmacologic treatment are prevalent in persons with serious and persistent mental illness. Obesity is difficult to reverse, but behavioral programs involving diet and exercise are sometimes successful. METHOD: Patients with serious and persistent mental illness living in the community were enrolled voluntarily into the Solutions for Wellness Personalized Program. Participants completed an enrollment survey that provided information for the creation of an individualized management plan that included nutrition, exercise, stress management, and sleep improvement components. Weight, body mass index (BMI, kg/m(2)), behavior, and attitudes were assessed at baseline (enrollment) and monthly for 6 months. RESULTS: During the period of July 1, 2002, through June 30, 2003, 7188 patients with serious and persistent mental illness had enrolled in the program, and 83% were either overweight or obese. Follow-up survey responses taken at 6-month endpoint from finishers (N = 1422) indicated that positive changes were made in diet (91%), exercise (85%), reduced stress (93.8%), and sleep (92.9%). Significant decreases in BMI were associated with changes in diet (p = .014) and exercise (p = .035). In addition, 97% of participants reported that they were at least somewhat confident in the ability to maintain lifestyle changes, and this confidence was significantly (p < .001) associated with reaching dietary and exercise goals. CONCLUSIONS: Patients suffering from serious and persistent mental illness may benefit from participating in wellness intervention programs.     

Clozapine-induced weight gain predicts improvement in psychopathology

BACKGROUND: Some, but not all, previous studies have indicated that weight gain is associated with greater improvement in psychopathology during clozapine treatment. Possible reasons for the inconsistent results include failure to adjust for initial body weight and level of psychopathology, differences in trial duration, outcome measures, reliability of assessment, concomitant medications and clozapine dosage. The purpose of this study was to test the hypothesis that clozapine-induced weight gain is related to antipsychotic efficacy at 6 weeks and 6 months after adjusting for initial body weight and severity of illness. METHODS: Weight and psychopathology were determined in 74 patients with schizophrenia or schizoaffective disorder at baseline and after 6 weeks and 6 months of open treatment with clozapine monotherapy. The primary measures of psychopathology were the Brief Psychiatric Rating Scale (BPRS) Total and Positive symptoms subscales, Schedule for Assessment of Negative Symptoms (SANS), Schedule for Assessment of Positive Symptoms (SAPS) and Global Assessment of Function Scale (GAFS). RESULTS: Significant improvement in the key measures of psychopathology was noted at 6 weeks and 6 months. Mean weight gains at 6 weeks and 6 months were 3.7+/-5.7 S.D. and 7.3+/-7.9 S.D. kg, respectively, with the increase between 6 weeks and 6 months being significant. Age, but not gender, initial body weight, clozapine dosage or plasma levels predicted weight gain at both time points. At 6 weeks and 6 months, after adjustment for age, initial weight and level of psychopathology, the percentage change in weight significantly predicted the improvement in the BPRS Total and Positive symptoms subscale, the SANS Global score, as well as other measures of psychopathology. CONCLUSIONS: Increase in weight with clozapine predicted improvement in psychopathology. This suggests that effects of clozapine on neurotransmitters which influence weight gain, e.g. 5-HT(2C) and 5-HT(1a) antagonism, in association with individual variations in these receptors and others molecules, e.g. peptides and transporters, due to polymorphisms or post-translational editing of mRNAs, may also contribute to the improvement in psychopathology.     

Fluphenazine dose, clinical response, and extrapyramidal symptoms during acute treatment

Fifty-three patients with acute exacerbations of Research Diagnostic Criteria schizophrenic, schizoaffective (mainly schizophrenic), and other nonaffective psychoses completed 24 or 28 days of treatment with randomized, fixed, double-blind doses of 10, 20, or 30 mg of oral fluphenazine hydrochloride daily. In the sample as a whole, improvement was not predicted by dose but was negatively related to duration of illness and of lifetime hospitalization, and to the presence of akathisia during the study (which was unrelated to chronicity). But among patients showing 40% or greater improvement in positive symptoms, percent improvement was predicted by dose and dose per kilogram of body weight; this was not the case for negative symptoms. Severity of acute extrapyramidal symptoms (excluding acute dystonia, dyskinesia, and akathisia) was significantly correlated with dosage per kilogram. Doses greater than 0.2 mg/kg per day were associated with greater clinical improvement but also with a high incidence of extrapyramidal symptoms; doses over 0.3 mg/kg per day were associated with more severe extrapyramidal symptoms. These preliminary results suggest that there is a linear relationship between fluphenazine dosage and acute outcome, and that this relationship is observed in patients whose conditions improve to a criterion level. It is suggested that the nonresponder group may include many patients in whom dose is not relevant because they are unable (for a variety of reasons) to respond to the study treatment conditions; excluding them from analysis may allow a significant dose-response relationship to be observed. Akathisia deserves further study as a possible predictor of nonresponse.     

Effects of Regular Treadmill Exercise on a DNA Oxidative-Damage Marker and Total Antioxidant Capacity in Rat Hippocampal Tissue

MethodsThis study investigated the effects of 8 weeks of regular treadmill exercise on 8-OHdG and the TAC of hippocampal tissue in lead-acetate-exposed rats. Wistar rats were randomly divided into four groups: baseline, sham (control), lead, and exercise+lead. The exercise program involved running on a treadmill with increasing intensity five times a week for 8 weeks. Animals in the lead and exercise+lead groups received lead acetate at 20 mg/kg body weight intraperitoneally three times weekly for 8 weeks. Animals in the sham group received solvent (ethyl oleate) at 30 mg/kg body weight three times weekly for 8 weeks. TAC and 8-OHdG were measured by spectrophotometric and ELISA techniques, respectively. Data were analyzed by ANOVA and Tukey''s post-hoc test with a significance cutoff of p≤0.05.ResultsThe level of 8-OHdG and the TAC were significantly higher and lower, respectively, in the lead group than in the baseline and sham groups (p<0.01). However, the 8-OHdG level and TAC value in hippocampal tissue were significantly decreased and increased, respectively, in the exercise+lead group relative to the lead group (p<0.05).ConclusionsThe TAC of hippocampal tissue may be directly associated with neural protection mechanisms of exercise following lead acetate injection, and the beneficial effects of regular exercise in preventing hippocampal neuronal damage could be due to decreased hippocampal oxidative stress such as reflected by a lower 8-OHdG level and increased TAC.     

Mirtazapine augmentation enhances cognitive and reduces negative symptoms in schizophrenia patients treated with risperidone: a randomized controlled trial

This preliminary study aimed to determine if adding mirtazapine to risperidone might improve negative and cognitive symptoms in schizophrenia. In an 8-week, double-blind clinical trial, we randomly assigned 21 stabilized outpatients with schizophrenia undergoing risperidone treatment to adjunctive treatment with either mirtazapine or a placebo. The mirtazapine group exhibited a statistically significant improvement in cognitive function, including vocabulary and immediate memory, and negative symptoms (as measured by negative symptom scales) and showed an adverse effect of 5.83 kg mean weight gain. This study suggests augmenting risperidone with mirtazapine can effectively improve both negative and some cognitive symptoms of schizophrenia.

Research highlights

? Mirtazapine enhances some cognitive symptoms of schizophrenia. ? Mirtazapine reduces negative symptoms of schizophrenia.     

Nutritional intervention to prevent weight gain in patients commenced on olanzapine: a randomized controlled trial

OBJECTIVE: Olanzapine is the most commonly prescribed atypical antipsychotic medication in Australia. Research reports an average weight gain of between 4.5 and 7 kg in the 3 months following its commencement. Trying to minimize this weight gain in a population with an already high prevalence of obesity, mortality and morbidity is of clinical and social importance. This randomized controlled trial investigated the impact of individual nutrition education provided by a dietitian on weight gain in the 3 and 6 months following the commencement of olanzapine. METHOD: Fifty-one individuals (29 females, 22 males) who had started on olanzapine in the previous 3 months (mean length of 27 days +/- 20) were recruited through Peninsula Health Psychiatric Services and were randomly assigned to either the intervention (n = 29) or the control group (n = 22). Individuals in the intervention group received six 1 hour nutrition education sessions over a 3-month period. Weight, waist circumference, body mass index (BMI) and qualitative measures of exercise levels, quality of life, health and body image were collected at baseline at 3 and 6 months. RESULTS: After 3 months, the control group had gained significantly more weight than the treatment group (6.0 kg vs 2.0 kg, p < or = 0.002). Weight gain of more than 7% of initial weight occurred in 64% of the control group compared to 13% of the treatment group. The control group's BMI increased significantly more than the treatment group's (2 kg/m(2)vs 0.7 kg/m(2), p < or = 0.03). The treatment group reported significantly greater improvements in moderate exercise levels, quality of life, health and body image compared to the controls. At 6 months, the control group continued to show significantly more weight gain since baseline than the treatment group (9.9 kg vs 2.0 kg, p < or = 0.013) and consequently had significantly greater increases in BMI (3.2 kg/m(2)vs 0.8 kg/m(2), p < or = 0.017). CONCLUSION: Individual nutritional intervention provided by a dietitian is highly successful at preventing olanzapine-induced weight gain.     

Effects of mazindol in two patients with Prader-Willi syndrome

Two patients with Prader-Willi syndrome, including gross obesity with food-related behavior and mild mental retardation, are presented. One patient was an 11-year-old girl with the diagnosis of development delay, hypoactivity, and waxy skin with normal female karyotype. The other patient was a 15-year-old girl with the diagnosis of abnormal chromosome 15. Obesity had been present since early childhood, and it was difficult for them to manage their weight control by means of diet and exercise therapy. With 24-week mazindol administration, they demonstrated marked improvement in weight control during the early period and improvement in pathologic behavior without side effects. Mazindol was given orally, 1.0–2.0 mg/day, in one or two daily doses. Mazindol may prove to be useful in the treatment of patients with Prader-Willi syndrome.     

Effectiveness of a structured diet program in antipsychotic-induced weight gain in patients with schizophrenia

Objective.The aim of this study was to evaluate the effectiveness of a structured diet program in weight loss in patients with schizophrenia. Methods. A total of 38 outpatients diagnosed with schizophrenia according to DSM-IV and who had complaints of weight gain during treatment with various antipsychotic drugs were invited to participate in a 3-month structured diet program. Thirty-two patients and another 40 patients were included as the control group. At the beginning of the diet program, the patients were given a form in order to evaluate their eating habits, and blood samples were taken to measure plasma lipid profile, and fasting blood glucose (FBG) level. Patients’ baseline weight, body mass index (BMI), and basal metabolism rate (BMR) were recorded. Results. Thirty-two patients with schizophrenia, who attended a 3-month structured diet program had mean weight loss of 6.19 kg, whereas patients in the control group gained 1.6 kg. Conclusion. Our findings show that a diet program is effective in managing antipsychotic-induced weight gain. The degree of weight loss seems to be correlated with the duration in which the patient is on the diet program. However; younger patients had less benefit from the diet program.     

Patient outcomes in schizophrenia I: correlates with sociodemographic variables, psychopathology, and side effects.

OBJECTIVE: The present cross-sectional study examined the relationships of psychopathology, side effects, and sociodemographic factors with treatment outcomes in terms of patients' quality of life (QOL), functioning, and needs for care. METHOD: Sixty outpatients with chronic schizophrenia who had been treated with either clozapine or olanzapine for at least 6 months were investigated. RESULTS: Most psychopathological symptoms as well as psychic side effects, weight gain, and female sex were associated with lower QOL, while cognitive symptoms correlated with better QOL. Female sex, cognitive symptoms, and parkinsonism negatively influenced occupational functioning, and negative symptoms determined a lesser likelihood of living independently. Age, education, depression/anxiety, negative symptoms, and psychic side effects were predictors of patients' needs for care. CONCLUSION: Our results highlight the complex nature of patient outcomes in schizophrenia. They reemphasize the need of targeting effectiveness, i.e. both symptomatic improvement as well as drug safety, in such patients.     

The long-term effect of quetiapine (Seroquel TM ) monotherapy on weight in patients with schizophrenia

INTRODUCTION: Quetiapine (Seroquel TM ) is an atypical antipsychoticdrug with demonstrated efficacy and tolerability. In particular, placebo-level extrapyramidal symptoms (EPS) across the entire dose range and a low propensity to cause sexual dysfunction suggest it may be associated with greater patient acceptability than alternative treatments. However, other side-effects, such as weight gain, may also have a significant impact on treatment acceptability. METHOD: We report the long-term weight changes observed in a cohort of 427 patients with schizophrenia from controlled and open-label extension (OLE) trials, in which quetiapine (mean dose 475 mg/day after 1 year) was the only antipsychotic medication during the OLE period. RESULTS: In these patients, there was no overall effect on weight across the body mass index (BMI) spectrum. There were no dose-related effects on weight, and only one patient withdrew from treatment due to an adverse event of weight gain. Quetiapine appeared to have a weightneutral or 'normalizing' effect, with a tendency towards favourable shifts in bodyweight in underweight patients (BMI<18.5 kg/m 2 ) and severely obese patients (BMI>35 kg/m 2 ). CONCLUSION: These results indicate that long-term weight changes with quetiapine monotherapy are minimal and potentially beneficial, and do not appear to raise the medical concerns associated with some other atypical agents.