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[The association of schizophrenia with chronic non transmissible diseases].
Orellana, G, Rodríguez, M, González, N, Durán, E
Revista medica de Chile. 2017;(8):1047-1053
Abstract
The life expectancy of patients with schizophrenia (SCH) is 11 to 20 years less than the general population. There is an association between SCH and various diseases and chronic conditions, highlighting the cardio-metabolic diseases. This association has been attributed to the use of antipsychotics, however, evidence has also shown intrinsic susceptibility of schizophrenic patients the development of chronic conditions. This review aims to update knowledge about chronic conditions such as cardiometabolic risk and sleep, bone and kidney disorders related to SCH. These patients have a high prevalence of risk behaviors, including smoking and poor diet. They have a worse metabolic profile than the general population and a greater likelihood of developing metabolic syndrome, diabetes and cardiovascular disease. SCH has also been associated with other chronic diseases such as osteoporosis and chronic kidney disease. The high prevalence of these comorbidities in schizophrenic population is not explained solely by the antipsychotic treatment, therefore intrinsic mechanisms associated to SCH are postulated to be associated with these conditions. This new information requires a change in the multidisciplinary medical approach for the study and management of schizophrenic patients.
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Cardiometabolic Risks in Schizophrenia and Directions for Intervention, 1: Magnitude and Moderators of the Problem.
Andrade, C
The Journal of clinical psychiatry. 2016;(7):e844-7
Abstract
Patients with schizophrenia have increased prevalence rates for many cardiac risk factors. As an example, the metabolic syndrome is common in schizophrenia, with elevated rates for the syndrome and its components evident in first-episode schizophrenia patients, itself. These rates are further elevated in multiepisode patients. Weight gain is a clinical marker of cardiometabolic risk. Antipsychotic drug treatment may drive at least part of the increased cardiometabolic risk; the effects are externally evident in the form of weight gain, with different drugs having different effects on weight and metabolic parameters. Finally, sedentariness and smoking are 2 common behaviors that increase cardiometabolic risks in schizophrenia. It is important for psychiatrists who treat schizophrenia to evaluate the cardiometabolic risks in their patients so that appropriate lifestyle and pharmacologic interventions can be planned.
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Aripiprazole-Induced Hyperlipidemia: An Update.
Tarraf, C, Naja, WJ
The primary care companion for CNS disorders. 2016;(4)
Abstract
OBJECTIVE To review the literature on the metabolic side effects of aripiprazole. Three cases of aripiprazole-induced hypertriglyceridemia are also presented. DATA SOURCES A search was conducted of English-language articles and abstracts (meta-analyses, randomized controlled trials, clinical trials, naturalistic open-label trials, reviews, and case reports) published up to August 31, 2014, in electronic databases (PubMed, MEDLINE). STUDY SELECTION Free-text and MeSH search keywords included aripiprazole, cholesterol, triglyceride, lipid profile, hyperlipidemia, and hypercholesterolemia and their differing terminations and combinations. The search was supplemented by a manual review of reference lists from the identified publications. Pediatric studies were excluded. DATA EXTRACTION Twenty-two articles were found and 3 aspects of the metabolic side effects of aripiprazole were reviewed: (1) the prevalence of the metabolic syndrome in mentally ill patients prior to any antipsychotic use to highlight the initial predisposition of this group of patients to develop the metabolic syndrome, (2) the prevalence of metabolic changes depending on the choice of antipsychotic (aripiprazole compared to other antipsychotics), and (3) metabolic changes reported after switching from an antipsychotic to aripiprazole. RESULTS Patients with mental disorders are at high risk for developing dyslipidemia, diabetes, and the full criteria of the metabolic syndrome. Antipsychotic use exacerbates this risk, thus increasing the mortality in this population. Nevertheless, it seems that the risk for these side effects varies with each antipsychotic. Although by and large the literature supports the supposition that aripiprazole causes less metabolic effects than other antipsychotics, we report 3 cases of serious aripiprazole-related dyslipidemia in young subjects. CONCLUSION On the basis of these 3 cases, aripiprazole can cause hypertriglyceridemia. Triglyceride levels should be carefully monitored in patients with mental disorders taking aripiprazole.
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Adjunctive Aripiprazole Treatment for Risperidone-Induced Hyperprolactinemia: An 8-Week Randomized, Open-Label, Comparative Clinical Trial.
Zhao, J, Song, X, Ai, X, Gu, X, Huang, G, Li, X, Pang, L, Ding, M, Ding, S, Lv, L
PloS one. 2015;(10):e0139717
Abstract
OBJECTIVE The present study aimed to evaluate the efficacy and safety of adjunctive aripiprazole treatment in schizophrenia patients with risperidone-induced hyperprolactinemia. METHODS One hundred and thirteen patients who were receiving a stable dose of risperidone were randomly assigned to either adjunctive aripiprazole treatment (10 mg/day) (aripiprazole group) or no additional treatment (control group) at a 1:1 ratio for 8 weeks. Schizophrenia symptoms were measured using the Positive and Negative Syndrome Scale (PANSS). Rating scales and safety assessments (RSESE, BARS, UKU) were performed at baseline and at weeks 4 and 8. Serum levels of prolactin were determined at baseline and at weeks 2, 4, 6 and 8. Metabolic parameters were determined at baseline and again at weeks 4 and 8. RESULTS One hundred and thirteen patients were enrolled in this study, and 107 patients completed the study (54 in the aripiprazole group, and 53 in the control group). PANSS-total scores in the aripiprazole group decreased significantly at week 4 (P = 0.003) and week 8 (P = 0.007) compared with the control group. PANSS-negative scores in the aripiprazole group also decreased significantly at week 4 (P = 0.005) and week 8 (P< 0.001) compared with the control group. Serum levels of prolactin in the aripiprazole group decreased significantly at week 2 (P< 0.001), week 4 (P< 0.001), week 6 (P< 0.001) and week 8 (P< 0.001) compared with the control group. There were no significant differences in changes of Fasting Plasma Glucose, Total cholesterol, Triglycerides and High Density Lipoprotein within each group at week 4 and 8 execpt low density lipoproteins. There was no significant difference in the incidence of adverse reactions between the two groups. CONCLUSIONS Adjunctive aripiprazole treatment may be beneficial in reducing serum levels of prolactin and improving negative symptoms in schizophrenia patients with risperidone-induced hyperprolactinemia. TRIAL REGISTRATION chictr.org ChiCTR-IOR-15006278.
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Metabolomic profiling of schizophrenia patients at risk for metabolic syndrome.
Paredes, RM, Quinones, M, Marballi, K, Gao, X, Valdez, C, Ahuja, SS, Velligan, D, Walss-Bass, C
The international journal of neuropsychopharmacology. 2014;(8):1139-48
Abstract
Second-generation antipsychotics (SGAs) are commonly used to treat schizophrenia. However, SGAs cause metabolic disturbances that can manifest as metabolic syndrome (MetS) in a subset of patients. The causes for these metabolic disturbances remain unclear. We performed a comprehensive metabolomic profiling of 60 schizophrenia patients undergoing treatment with SGAs that puts them at high (clozapine, olanzapine), medium (quetiapine, risperidone), or low (ziprasidone, aripiprazole) risk for developing MetS, compared to a cohort of 20 healthy controls. Multiplex immunoassays were used to measure 13 metabolic hormones and adipokines in plasma. Mass spectrometry was used to determine levels of lipids and polar metabolites in 29 patients and 10 controls. We found that levels of insulin and tumor necrosis factor alpha (TNF-α) were significantly higher (p < 0.005) in patients at medium and high risk for MetS, compared to controls. These molecules are known to be increased in individuals with high body fat content and obesity. On the other hand, adiponectin, a molecule responsible for control of food intake and body weight, was significantly decreased in patients at medium and high risk for MetS (p < 0.005). Further, levels of dyacylglycerides (DG), tryacylglycerides (TG) and cholestenone were increased, whereas α-Ketoglutarate and malate, important mediators of the tricarboxylic acid (TCA) cycle, were significantly decreased in patients compared to controls. Our studies suggest that high- and medium-risk SGAs are associated with disruption of energy metabolism pathways. These findings may shed light on the molecular underpinnings of antipsychotic-induced MetS and aid in design of novel therapeutic approaches to reduce the side effects associated with these drugs.
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Effects of switching from olanzapine, quetiapine, and risperidone to aripiprazole on 10-year coronary heart disease risk and metabolic syndrome status: results from a randomized controlled trial.
Stroup, TS, Byerly, MJ, Nasrallah, HA, Ray, N, Khan, AY, Lamberti, JS, Glick, ID, Steinbook, RM, McEvoy, JP, Hamer, RM
Schizophrenia research. 2013;(1-3):190-5
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Abstract
PURPOSE This study examined the clinical significance of switching from olanzapine, quetiapine, or risperidone to aripiprazole by examining changes in predicted risk of cardiovascular disease (CVD) according to the Framingham Risk Score (FRS) and metabolic syndrome status. FRS estimates 10-year risk of "hard" coronary heart disease (CHD) outcomes (myocardial infarction and coronary death) while metabolic syndrome is associated with increased risk of CVD, stroke, and diabetes mellitus. METHOD Changes in FRS and metabolic syndrome status were compared between patients with BMI ≥ 27 and non-HDL-C ≥ 130 mg/dL randomly assigned to stay on stable current treatment (olanzapine, quetiapine, or risperidone) or switch to treatment with aripiprazole with 24 weeks of follow-up. All study participants were enrolled in a behavioral program that promoted healthy diet and exercise. RESULTS The pre-specified analyses included 89 switchers and 98 stayers who had post-baseline measurements needed to assess changes. Least squares mean estimates of 10-year CHD risk decreased more for the switch (from 7.0% to 5.2%) than the stay group (from 7.4% to 6.4%) (p = 0.0429). The odds ratio for having metabolic syndrome (stay vs. switch) at the last observation was 1.748 (95% CI 0.919, 3.324, p = 0.0885). CONCLUSION Switching from olanzapine, quetiapine, or risperidone to aripiprazole was associated with larger reductions in predicted 10-year risk of CHD than the behavioral program alone. The advantage of switching on metabolic syndrome was not statistically significant. The benefits of switching must be balanced against its risks, which in this study included more discontinuations of the study treatment but no significant increase in symptoms or hospitalizations.
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A randomized placebo-controlled trial of an omega-3 fatty acid and vitamins E+C in schizophrenia.
Bentsen, H, Osnes, K, Refsum, H, Solberg, DK, Bøhmer, T
Translational psychiatry. 2013;(12):e335
Abstract
Membrane lipid metabolism and redox regulation may be disturbed in schizophrenia. We examined the clinical effect of adding an omega-3 fatty acid and/or vitamins E+C to antipsychotics. It was hypothesized that lower baseline levels of polyunsaturated fatty acids (PUFAs) would predict more benefit from the add-on treatment. The trial had a multicenter, randomized, double-blind, placebo-controlled 2 × 2 factorial design. Patients aged 18-39 years with schizophrenia or related psychoses were consecutively included at admission to psychiatric departments in Norway. They received active or placebo ethyl-eicosapentaenoate (EPA) 2 g day⁻¹ and active or placebo vitamin E 364 mg day⁻¹+vitamin C 1000 mg day⁻¹ (vitamins) for 16 weeks. The main outcome measures were Positive and Negative Syndrome Scale (PANSS) total and subscales scores, analyzed by linear mixed models. Ninety-nine patients were included. At baseline, erythrocyte PUFA were measured in 97 subjects. Given separately, EPA and vitamins increased drop-out rates, whereas when combined they did not differ from placebo. In low PUFA patients, EPA alone impaired the course of total PANSS (Cohen's d=0.29; P=0.03) and psychotic symptoms (d=0.40; P=0.003), especially persecutory delusions (d=0.48; P=0.0004). Vitamins alone impaired the course of psychotic symptoms (d= 0.37; P=0.005), especially persecutory delusions (d=0.47; P=0.0005). Adding vitamins to EPA neutralized the detrimental effect on psychosis (interaction d=0.31; P=0.02). In high PUFA patients, there were no significant effects of trial drugs on PANSS scales. In conclusion, given separately during an acute episode, EPA and vitamins E+C induce psychotic symptoms in patients with low levels of PUFA. Combined, these agents seem safe.
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A randomized controlled trial undertaken to test a nurse-led weight management and exercise intervention designed for people with serious mental illness who take second generation antipsychotics.
Usher, K, Park, T, Foster, K, Buettner, P
Journal of advanced nursing. 2013;(7):1539-48
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AIM: To test the effect of a nurse-led intervention on weight gain in people with serious mental illness prescribed and taking second generation antipsychotic medication. BACKGROUND Weight gain and obesity has reached epidemic proportions in the general population with the prevalence of Metabolic Syndrome reaching 20-25% of the global population. People with serious mental illness are at even higher risk, particularly those taking second generation antipsychotic medication. DESIGN An experimental randomized controlled trial was undertaken. METHOD The control group received a 12-week healthy lifestyle booklet. In addition to the booklet, the intervention group received weekly nutrition and exercise education, exercise sessions, and nurse support. Participants (n = 101) were assessed at baseline and 12 weeks. Data were collected between March 2008-December 2010. Seven outcome measures were used: body measurements included girth (cm), weight (kg), height (cm), and body mass index (kg/m(2) ); questionnaires included the medication compliance questionnaire, the Drug Attitude Inventory, the Liverpool University Neuroleptic Side Effect Rating Scale, and the Medical Outcomes Study Short Form 36. Differences in primary outcome measures between baseline and 12 weeks follow-up were compared between intervention and control groups using standard bi-variate statistical tests. The study was conducted between 2008-2010. RESULTS The analysis of outcome measures for the control group (n = 50) and intervention group (n = 51) was not statistically significant. There was a mean weight change of -0·74 kg at 12 weeks for the intervention group (n = 51), while the control group (n = 50) had a mean weight change of -0·17 kg at 12 weeks. CONCLUSION The results were not statistically significant.
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Comparison of fasting blood sugar and serum lipid profile changes after treatment with atypical antipsychotics olanzapine and risperidone.
Kaushal, J, Bhutani, G, Gupta, R
Singapore medical journal. 2012;(7):488-92
Abstract
INTRODUCTION This study aimed to compare the effects of the two most commonly prescribed atypical antipsychotics, olanzapine and risperidone, on fasting blood sugar and serum lipid profile of the recipients. METHODS A randomised, comparative, open clinical study was conducted on 60 schizophrenic patients. The patients were divided into two groups, one receiving olanzapine and the other receiving risperidone. The patients were assessed for changes in fasting blood sugar and serum lipid profile (triglycerides [TG], high-density lipoprotein [HDL], low-density lipoprotein [LDL], very-low-density lipoprotein [VLDL] and total cholesterol) eight weeks after starting treatment. The number of patients positive for fasting blood sugar and lipid profile criteria of metabolic syndrome was calculated by applying the modified National Cholesterol Education Programme Adult Treatment Panel III guidelines (NCEP ATP III) criteria at eight weeks. RESULTS Patients treated with olanzapine showed a highly significant increase in the observed parameters, whereas those treated with risperidone showed a significant increase in fasting blood sugar, HDL and LDL levels, and a highly significant increase in other parameters. Intergroup comparison was insignificant except for TG, VLDL and total cholesterol levels. More men as compared to women fulfilled the NCEP ATP III criteria for metabolic syndrome in both groups. CONCLUSION Olanzapine has a higher propensity to cause derangement of some parameters of lipid profile than risperidone. These parameters include TG, VLDL and total cholesterol levels.
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[Atypical antipsychotic induced weight gain and metabolic disorders].
Rojas G, P, Poblete A, C, Orellana G, X, Rouliez A, K, Liberman G, C
Revista medica de Chile. 2009;(1):106-14
Abstract
The advent of new antipsychotic drugs has improved the treatment of schizophrenic patients as well as those suffering from other severe psychiatric disorders. Its widespread use, however, has been associated to the development of obesity and metabolic disturbances such as diabetes mellitus, dyslipidemia and increased coronary risk. This has caused a serious concern, due to the high cardiovascular mortality that prematurely affects these patients. The etiology of these abnormalities is still a matter of debate, although it is generally believed that the new antipsychotic drugs have a control stimulating effect on appetite, and their use is associated to an increased level of cortisol and to an insulin-resistance state. In addition, there is an increase in inflammatory mediator and cytokine production, induced by the pathophysiology of the schizophrenic process itself and also caused by the direct action of the antipsychotic drugs. In spite of the mounting evidence, the metabolic management of these patients is still deficient. A close follow-up in the initial stages of the antipsychotic treatment is recommended, as well as giving advice about diet and physical exercise. Finally, when obesity or other conditions associated to metabolic syndrome appear, the recommendation is to switch to drugs with less secondary effects or to add adjuvant medications to improve the overall evolution of these patients.