background The relative effectiveness of second-generation (atypical) antipsychotic drugs as compared with that of older agents has been incompletely addressed, though newer agents are currently used far more commonly. We compared a first-generation antipsychotic, perphenazine, with several newer drugs in a double-blind study. methods A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and randomly assigned to receive olanzapine (7.5 to 30 mg per day), perphenazine (8 to 32 mg per day), quetiapine (200 to 800 mg per day), or risperidone (1.5 to 6.0 mg per day) for up to 18 months. Ziprasidone (40 to 160 mg per day) was included after its approval by the Food and Drug Administration. The primary aim was to delineate differences in the overall effectiveness of these five treatments. results Overall, 74 percent of patients discontinued the study medication before 18 months (1061 of the 1432 patients who received at least one dose): 64 percent of those assigned to olanzapine, 75 percent of those assigned to perphenazine, 82 percent of those assigned to quetiapine, 74 percent of those assigned to risperidone, and 79 percent of those assigned to ziprasidone. The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine (P<0.001) or risperidone (P=0.002) group, but not in the perphenazine (P=0.021) or ziprasidone (P=0.028) group. The times to discontinuation because of intolerable side effects were similar among the groups, but the rates differed (P=0.04); olanzapine was associated with more discontinuation for weight gain or metabolic effects, and perphenazine was associated with more discontinuation for extrapyramidal effects. conclusions The majority of patients in each group discontinued their assigned treatment owing to inefficacy or intolerable side effects or for other reasons. Olanzapine was the most effective in terms of the rates of discontinuation, and the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine, risperidone, and ziprasidone. Olanzapine was associated with greater weight gain and increases in measures of glucose and lipid metabolism.

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Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia

Improving diet and lifestyle is a critical component of the American Heart Association's strategy for cardiovascular disease risk reduction in the general population. This document presents recommendations designed to meet this objective. Specific goals are to consume an overall healthy diet; aim for a healthy body weight; aim for recommended levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides; aim for normal blood pressure; aim for a normal blood glucose level; be physically active; and avoid use of and exposure to tobacco products. The recommendations are to balance caloric intake and physical activity to achieve and maintain a healthy body weight; consume a diet rich in vegetables and fruits; choose whole-grain, high-fiber foods; consume fish, especially oily fish, at least twice a week; limit intake of saturated fat to 7% of energy, trans fat to 1% of energy, and cholesterol to 300 mg/day by choosing lean meats and vegetable alternatives, fat-free (skim) or low-fat (1% fat) dairy products and minimize intake of partially hydrogenated fats; minimize intake of beverages and foods with added sugars; choose and prepare foods with little or no salt; if you consume alcohol, do so in moderation; and when you eat food prepared outside of the home, follow these Diet and Lifestyle Recommendations. By adhering to these diet and lifestyle recommendations, Americans can substantially reduce their risk of developing cardiovascular disease, which remains the leading cause of morbidity and mortality in the United States. (Circulation. 2006;114:82-96.)

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Diet and Lifestyle Recommendations Revision 2006 A Scientific Statement From the American Heart Association Nutrition Committee

Background: Knowledge of the number of deaths caused by risk factors is needed for health policy and priority setting. Our aim was to estimate the mortality effects of the following 12 modifiable dietary, lifestyle, and metabolic risk factors in the United States (US) using consistent and comparable methods: high blood glucose, low-density lipoprotein (LDL) cholesterol, and blood pressure; overweight–obesity; high dietary trans fatty acids and salt; low dietary polyunsaturated fatty acids, omega-3 fatty acids (seafood), and fruits and vegetables; physical inactivity; alcohol use; and tobacco smoking. Methods and Findings: We used data on risk factor exposures in the US population from nationally representative health surveys and disease-specific mortality statistics from the National Center for Health Statistics. We obtained the etiological effects of risk factors on disease-specific mortality, by age, from systematic reviews and meta-analyses of epidemiological studies that had adjusted (i) for major potential confounders, and (ii) where possible for regression dilution bias. We estimated the number of disease-specific deaths attributable to all non-optimal levels of each risk factor exposure, by age and sex. In 2005, tobacco smoking and high blood pressure were responsible for an estimated 467,000 (95% confidence interval [CI] 436,000–500,000) and 395,000 (372,000–414,000) deaths, accounting for about one in five or six deaths in US adults. Overweight–obesity (216,000; 188,000–237,000) and physical inactivity (191,000; 164,000–222,000) were each responsible for nearly 1 in 10 deaths. High dietary salt (102,000; 97,000–107,000), low dietary omega-3 fatty acids (84,000; 72,000–96,000), and high dietary trans fatty acids (82,000; 63,000–97,000) were the dietary risks with the largest mortality effects. Although 26,000 (23,000–40,000) deaths from ischemic heart disease, ischemic stroke, and diabetes were averted by current alcohol use, they were outweighed by 90,000 (88,000–94,000) deaths from other cardiovascular diseases, cancers, liver cirrhosis, pancreatitis, alcohol use disorders, road traffic and other injuries, and violence. Conclusions: Smoking and high blood pressure, which both have effective interventions, are responsible for the largest number of deaths in the US. Other dietary, lifestyle, and metabolic risk factors for chronic diseases also cause a substantial number of deaths in the US. Please see later in the article for the Editors’ Summary.

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The Preventable Causes of Death in the United States: Comparative Risk Assessment of Dietary, Lifestyle, and Metabolic Risk Factors

Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials

http://wealthandhealth.ltd.uk/over100/origins%20of%20western%20diet.pdf

Origins and evolution of the Western diet: health implications for the 21st century

OBJECTIVE: The purpose of this study was to estimate and compare the effects of anti­psychotics—both the newer ones and the conventional ones—on body weight. METHOD: A comprehensive literature search identified 81 English- and non-English-language articles that included data on weight change in antipsychotic-treated patients. For each agent, a meta-analysis and random effects metaregression estimated the weight change after 10 weeks of treatment at a standard dose. A comprehensive narrative review was also conducted on all articles that did not yield quantitative information but did yield important qualitative information. RESULTS: Placebo was associated with a mean weight reduction of 0.74 kg. Among conventional agents, mean weight change ranged from a reduction of 0.39 kg with molindone to an increase of 3.19 kg with thioridazine. Among newer antipsychotic agents, mean increases were as follows: clozapine, 4.45 kg; olanzapine, 4.15 kg; sertindole, 2.92 kg; risperidone, 2.10 kg; and ziprasidone, 0.04 kg....

https://ajp.psychiatryonline.org/doi/pdf/10.1176/ajp.156.11.1686

Antipsychotic-Induced Weight Gain: A Comprehensive Research Synthesis

Objective To estimate mean level of trans fatty acid intakes using a representative sample of the US population. Design The study used food intake data from the 1989-1991 Continuing Survey of Food Intakes by Individuals (CSFII) and the trans fatty acid contents of specific foods calculated from a database compiled by the US Department of Agriculture (USDA) to estimate the mean level and deciles of trans fatty acid intake of the representative US population. Subjects/setting Trans fatty acid intakes were estimated for each subject (N=11,258) in the CSFII data who completed both a 24-hour recall and a 2-day food record. Statistical analyses performed Weights developed by USDA for the survey were used for all data analyses. The Technical Assessment Systems (TAS) International Diet Research System (TAS-DIET), software developed by TAS, was used to derive weighted estimates of the mean and percentiles of the intake distribution. PC CARP, software designed by Iowa State University, was used to estimate standard errors. Results Mean percentage of energy ingested as trans fatty acids was 2.6% and the mean percentage of total fat ingested as trans fatty acids was 7.4%. Across all age and gender groups examined, estimates ranged from 2.6% to 2.8% and 7.1% to 7.9%, respectively. Applications/conclusions Dietetics practitioners can use the representative data of this study to help clients achieve desired changes in consumption levels of trans fatty acids. J Am Diet Assoc. 1999;99:166–174.

Estimated Intakes of Trans Fatty and Other Fatty Acids in the US Population

Genomewide searches for loci influencing complex human traits and diseases such as diabetes, hypertension, and obesity are often plagued by low power and interpretive difficulties. Attempts to remedy these difficulties have typically relied on, and have promoted the use of, novel subject-ascertainment schemes, larger sample sizes, a greater density of DNA markers, and more-sophisticated statistical modeling and analysis strategies. Many of these remedies can be costly to implement. We investigate the utility of a simple statistical model for the mapping of quantitative-trait loci that incorporates multiple phenotypic or diagnostic endpoints into a gene-mapping analysis. The approach considers finding a linear combination of multiple phenotypic values that maximizes the evidence for linkage to a locus. Our results suggest that substantial increases in the power to map loci can be obtained with the proposed technique, although the increase in power obtained is a function of the size and direction of the residual correlation among the phenotypes used in the analysis. Extensive simulation studies are described that justify these claims, for cases in which two phenotypic measures are analyzed. This approach can be easily extended to cover more-complex situations and may provide a basis for more insightful genetic-analysis paradigms.

Ming C. Infante

Papers

Antipsychotic-Induced Weight Gain: A Comprehensive Research Synthesis

Estimated Intakes of Trans Fatty and Other Fatty Acids in the US Population

Multiple phenotype modeling in gene-mapping studies of quantitative traits: power advantages.