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Query: UMLS:C0036341 (schizophrenia)
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Weight gain is associated with the use of many psychotropic medications, including antidepressants, mood stabilizers, antipsychotic drugs, and may have serious long term consequences: it can increase health risks, specifically from overweight (BMI = 25-29.9 kg/m2) to obesity (BMI > or =30 kg/m2), according to Body Mass Index (BMI), and the morbidity associated therewith in a substantial part of patients (hypertension, coronary heart desease, ischemic stroke, impaired glucose tolerance, diabetes mellitus, dyslipidemia, respiratory problems, osteoarthritis, cancer); according to patients, psychosocial consequences such as a sense of demoralization, physical discomfort and being the target of substantial social stigma are so intolerable that they may discontinue the treatment even if it is effective. The paper reviews actual epidemiological data concerning drug induced weight gain and associated health problems in psychiatric patients : there is a high risk of overweight, obesity, impaired glucose tolerance, diabetes mellitus, premature death, in patients with schizophrenia or bipolar disorder; and the effects of specific drugs on body weight: Tricyclic Antidepressants (TCA) induced weight gain correlated positively with dosage and duration of treatment, more pronounced with amitriptyline ; Selective Serotonin Reuptake Inhibitors (SSRI) decrease transiently bodyweight during the first few weeks of treatment and may then increase bodyweight; weight gain appears to be most prominent with some mood stabilizers (lithium, valproate); atypical antipsychotics tend to cause more weight gain than conventional ones and weight gain, diabetes, dyslipidemia, seem to be most severe with clozapine and olanzapine. Conceming the underlying mechanisms of drug induced weight gain, medications might interfere with central nervous functions regulating energy balance; patients report about: increase of appetite for sweet and fatty foods or "food craving" (antidepressants, mood stabilizers, antipsychotic drugs) and weight gain despite reduced appetite which can be explained by an altered resting metabolic rate (TCA, SSRI, Monoaminoxidase Inhibitors MAO I). According to current concepts, appetite and feeding are regulated by a complex of neurotransmitters, neuromodulators, cytokines and hormones interacting with the hypothalamus, including the leptin and the tumor necrosis factor system. The pharmacologic mechanisms underlying weight gain are presently poorly understood: maybe the different activities at some receptor systems may induce it, but also genetic predisposition. Understanding of the metabolic consequences of psychotropic drugs (weight gain, diabetes, dyslipidemia) is essential: the insulin-like effect of lithium is known; treatment with antipsychotic medications increases the risk of impaired glucose tolerance and diabetes mellitus. Several management options of weight gain are available from choosing or switching to another drug, dietary advices, increasing physical activities, behavioural treatment, but the best approach seems to attempt to prevent the weight gain : patients beginning maintenance therapy should be informed of that risk, and nutritional assessment and counselling should be a routine part of treatment management, associated with monitoring of weight, BMI, blood pressure, biological parameters (baseline and three months monitoring of fasting glucose level, fasting cholesterol and triglyceride levels, glycosylated haemoglobin). Psychiatrics must pay attention to concomitant medications and individual factors underlying overweight and obesity. Weight gain has been described since the discovery and the use of the firstpsychotropic drugs, but seems to intensify with especially some of the second generation antipsychotic medications ; understanding of the side effects of psychotropic drugs, including their metabolic consequences (weight gain, diabetes, dyslipidemia) is essential for the psychiatrics to avoid on the one hand a risk of lack of compliance, a discontinuation of the pharmacological medication and also a risk of relapse and rehospitalization, and on the other hand to avoid acute life threatening events (diabetic ketoacidocetosis and non ketotic hyperosmolar coma, long term risk complications of diabetes and overweight).
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PMID:[Psychotropic drugs induced weight gain: a review of the literature concerning epidemiological data, mechanisms and management]. 1638 18

Obesity and diabetes have caused problems for individuals with schizophrenia long before atypical antipsychotic agents. The prevalence of obesity, insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, dyslipidemia, and the Metabolic Syndrome has increased in people with schizophrenia as compared to the general population. Risk reduction studies for persons with obesity, diabetes, and cardiovascular disease indicate that cognitive/behavioral interventions that promote motivation and provide strategies to overcome the barriers in adherence to diet and activity modification are effective interventions for weight management and risk reduction. In the landmark multi-center randomized-controlled trial study, the Diabetes Prevention Project (DPP), a cognitive/behavioral intervention, was more successful in producing weight loss and preventing diabetes than the drugs metformin, troglitazone or placebo. This pilot study examined the effectiveness of a cognitive/behavioral group intervention, modified after the DPP program, in individuals with schizophrenia or schizoaffective disorder taking atypical antipsychotics in a large urban public mental health system. Outcome measures included body weight, body mass index, waist-hip ratios, and fasting glucose levels. Both groups demonstrated elevated fasting glucose levels and were obese with a mean BMI of 33. The group that received the cognitive/behavioral group intervention lost more weight than the treatment as usual group. The CB group participants lost an average of 5.4 lb or 2.9% of body weight, and those in the control group lost 1.3 lb or 0.6% body weight. The range of weight loss for the treatment group was from 1 to 20 lb. This pilot study has demonstrated that weight loss is possible with cognitive/behavioral interventions in a population with a psychotic disorder.
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PMID:A cognitive/behavioral group intervention for weight loss in patients treated with atypical antipsychotics. 1650 43

Metabolic abnormalities occur frequently in patients treated with antipsychotics and are of growing concern to clinicians. This study sought to determine whether antipsychotic-associated metabolic abnormalities identified through intensive monitoring can be reversed by switching to aripiprazole. Recent evidence suggests that aripiprazole may exhibit a favorable metabolic safety profile. The study population is a subset of a large (n > 500) ongoing prospective cohort. Thirty-one consecutive patients with schizophrenia who were started on aripiprazole were included in the study. All patients underwent an extensive metabolic evaluation, including an oral glucose tolerance test, at baseline, at 6 weeks, and at 3 months post switch. Metabolic abnormalities were defined as any of the following: new onset diabetes, impaired fasting glucose, impaired glucose tolerance, metabolic syndrome (MetS) according to various definitions, and dyslipidemia. After 3 months of treatment with aripiprazole (mean daily dose 16.3 mg), there was a significant decrease in body weight, body mass index, and waist circumference. There was a significant reduction in fasting glucose, fasting insulin, insulin resistance index, and serum lipids levels (cholesterol, triglycerides, low-density lipoprotein (LDL), LDL/HDL, Chol/HDL, and non-HDL cholesterol). There was also a significant reduction in prolactin levels. All 7 cases of recent onset diabetes were reversed at 3 months follow-up. The MetS was reversed in 50% of patients at 3 months follow-up. Our results support the reversibility of recent onset diabetes on antipsychotic medication when detected early and followed by a switch to aripiprazole.
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PMID:A case series: evaluation of the metabolic safety of aripiprazole. 1694 Mar 38

Compared with the general population, persons with schizophrenia have up to a 20% shorter lifespan, with cardiovascular disease as the leading cause of death. In addition, persons with schizophrenia have increased prevalence of the metabolic syndrome (obesity, insulin resistance, dyslipidemia, impaired glucose tolerance, and hypertension), increased prevalence of risk factors such as smoking, poverty, and poor nutrition, and reduced access to medical care. Results from the recent Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) provide further evidence of the metabolic risk associated with different atypical antipsychotics. Based on this study and a growing number of other randomized clinical trials, clozapine and olanzapine treatment can produce substantial mean changes in weight and an increased risk of associated metabolic disturbances. Risperidone and quetiapine treatment can produce intermediate changes in mean weight in comparison to treatment with other atypical antipsychotics, with discrepant results with respect to metabolic risk. Aripiprazole and ziprasidone treatment induced the lowest mean changes in weight gain and had no effect on risk for adverse metabolic changes, among currently available atypical agents. Considerable evidence indicates that mentally ill patients often do not receive adequate recognition of, monitoring of, or care for their medical illnesses. There is a critical need for psychiatrists and primary care professionals to increase awareness of and attention to the physical health problems of persons with mental illness, including appropriate management of metabolic adverse events associated with psychiatric medications.
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PMID:Metabolic considerations in the use of antipsychotic medications: a review of recent evidence. 1728 24

Second-generation (atypical) antipsychotic medications are of great benefit to a wide variety of people with psychiatric disorders, especially patients with schizophrenia. However, one constellation of adverse effects is an increased risk of obesity, diabetes, and metabolic syndrome. Increasing numbers of reports concerning impaired glucose tolerance, diabetes, and ketoacidosis have raised concerns about a possible association between abnormal glucose metabolism and treatment with atypical antipsychotics, although the question is still debated because of the presence of many confounding factors. A close relationship between drug-induced weight gain and risk of diabetes has been reported, emphasizing the role of insulin resistance. However, some cases of diabetes developed independently of weight gain, rather rapidly and possibly progressing to ketoacidosis, thus arguing for a severe impairment of insulin secretion. Another debated question is whether diabetes risk is a class action or a differential action. Although not fully scientifically proven yet, available evidence suggests that clozapine and olanzapine have a higher propensity to induce diabetes and metabolic syndrome compared with other atypical antipsychotic drugs, risperidone and quetiapine. Despite more limited available data, amisulpride, aripiprazole and ziprazidone showed less likelihood of precipitating diabetes. Interestingly, reversibility of drug-related diabetes has been reported with aripiprazole. The choice of atypical antipsychotic medication for a specific patient depends on many factors, but the likelihood of developing diabetes should become an important consideration. When prescribing an atypical antipsychotic, a commitment to careful baseline screening and follow-up monitoring is essential in order to mitigate the risk of developing diabetes and associated complications.
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PMID:Abnormal glucose metabolism in patients treated with antipsychotics. 1741 28

Thirty-nine patients suffering from coronary artery disease (CAD) and schizophrenia (main group) and 32 mentally healthy CAD patients (control group) were included in the study. Cardiological examination including complaint and anamnesis analysis, ECG, EchoCG, stress-EchoCG with dobutamine, 24-hour Holter ECG monitoring was performed; coronaroangiography was carried out in 15 patients. Acute circulatory insufficiency, early post-infarction stenocardia, and chronic left ventricular aneurism were found to be more frequent in patients with schizophrenia vs. controls. Certain differences in CAD risk factors between the groups were revealed. Hyperlipidemia and type 2 diabetes were found in 14 (36%) and 1 (3%) patients in the main group vs. 20 (62%) and 6 (19%) patients in the control group (p = 0.03; p = 0.04), respectively. Glucose intolerance was found in no schizophrenia patients, while it was revealed in 5 (16%) controls (p = 0.02). Patients with schizophrenia sought medical aid later than controls. The number of main group patients who sought medical aid during the first hour, the first 4 hours, the first 4 to 12 hours, or the first 12 to 24 hours was 2 (3%), 3 (5%), 16 (27%), and 38 (64%), respectively; in the control groups these numbers were 12 (30%), 21 (54%), 3 (8%), and 3 (8%), respectively (p < 0.001, p < 0.001, p = 0.02, p < 0.001, respectively).
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PMID:[The clinical features of the course of coronary artery disease in patients with schizophrenia]. 1756 35

Compared with the general population, persons with schizophrenia are characterized with an increased prevalence of obesity, type 2 diabetes mellitus, and cardiovascular disease. Weight gain and increased adiposity is associated with decreases in insulin sensitivity, leading to an increased risk of hyperglycaemia and hyperlipidemia. Antipsychotic drugs can increase adiposity and the range of trials suggests that treatment with antipsychotic medications may be associated with an increased risk of acute (ketoacidosis), subacute (weight gain, glucose intolerance, insulin resistance, dyslipidemia), and chronic (diabetes, hypertension, coronary heart disease) metabolic complications. Conclusions regarding the relative effects of various antipsychotic agents on different components of the metabolic syndrome were reviewed, as well as recommendations for monitoring these effects were noted. Selection and management of the antipsychotic agent reflects a balance between optimizing therapeutic effectiveness, modifying diet and exercise, and avoiding excessive weight gain, dyslipidemia, and insulin resistance.
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PMID:[Metabolic risk during antipsychotic treatment in patients with schizophrenia]. 1804 77

The PI3K-AKT network, which is activated by cytokines or growth factors, mediates intracellular signals to regulate a variety of cellular responses, including antiapoptosis, proliferation, cell cycling, protein synthesis, glucose metabolism, and telomere activity. Genomic mutations, alterations of the PI3K-AKT regulatory network, underlie such diseases as cancer, glucose intolerance (diabetes mellitus), schizophrenia, and/or autoimmune diseases. In addition to direct tumorigenesis involvement by genetically altering human cancer, the PI3K-AKT network underlies the clinical manifestation of different stages of tumorigenic viral infection, such as latent and chronic infection, and malignant transformation of Epstein-Barr, hepatitis C, hepatitis B, and human immunodeficiency virus (HIV) viruses. We summarize updated knowledge on the PI3K-AKT network underlying different phathological viral and/or bacterial infections. Antiviral activity engendered by suppressing of PI3K-AKT activity, rather than directly targeting anticancer activity via oncogenes, may thus open up ways to prevent malignant transformation by tumorigenic viral infection.
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PMID:[PI3K-AKT network roles in infectious diseases]. 1854 44

Signal detection methods were used to identify values of metabolic variables that predict development of prediabetes or diabetes before (moderators) or associated with treatment (mediators), utilizing data from two multi-center clinical trials of patients with schizophrenia, treated for 6 months with olanzapine (OLZ) or ziprasidone (ZIP). At baseline, participants were often overweight/obese (63% with a body mass index >or=25.0kg/m(2)), dyslipidemic [more than one-third had elevated triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) concentrations], and prediabetic (20%). Weight gain was significantly greater in OLZ-treated patients, as was accentuation of dyslipidemia. However, there were no significant correlations between weight gain and lipid changes from baseline to weeks 2, 4, 8 or to last observation. Type 2 diabetes developed in 4% and prediabetes in 18% of the population. Significant baseline predictors of diabetes were a HDL-C concentration <28mg/dL, or being >or=58-years-old if HDL-C concentration was >or=28mg/dL. Baseline plasma glucose concentration >or=92mg/dL was the only significant predictor of developing prediabetes, accounting for 60% of cases. Post-treatment increments in plasma TG concentrations >or=145mg/dL or >or=59mg/dL were significant predictors of diabetes (23%) or prediabetes (27%), respectively. If the increase in TG was <145mg/dL, rapid weight gain >or=6.1kg in 2 weeks predicted development of diabetes (18%). These findings provide a quantitative approach to identify those at greatest treatment-associated risk to develop glucose intolerance, and emphasize the need to address co-morbid medical disorders in these patients.
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PMID:In search of moderators and mediators of hyperglycemia with atypical antipsychotic treatment. 1926 68

This article reviews case reports and cohort studies involving antipsychotics and diabetes. The first part describes early case reports of new-onset glucose intolerance associated with chlorpromazine and lithium. The rest of the article presents findings from a literature review concerning atypical antipsychotics and the development of de novo diabetes mellitus or the exacerbation of already diagnosed diabetes mellitus. Evidence is presented from 3 types of sources: 1) case reports, 2) pharmacovigilance studies, and 3) retrospective reviews of treatment databases. The strengths and limitations of each of these methods are also discussed. Detailed tables are provided summarizing the findings from all 3 types of studies concerning all the currently available atypical antipsychotics. A discussion is included on the evidence for an association between atypical antipsychotics and an increased risk for diabetes mellitus. Further research is recommended to address important unanswered questions, such as what factors may confer an increased risk for patients with schizophrenia to develop diabetes.
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PMID:Antipsychotics and diabetes: case reports and cohort studies. 1966 53


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