Effects of nicotine nasal spray on cognitive function in schizophrenia.

Schizophrenics have among the highest rates of cigarette smoking. Some studies indicate that cigarette smoking or nicotine may ameliorate some of the cognitive or theoretically related neurophysiological deficits seen in schizophrenic patients. This study investigated the effects of nicotine nasal spray on measures of attention, verbal memory, and visual-spatial memory in schizophrenic patients who were chronic smokers, using a double-blind placebo-controlled pre-post experimental design. Compared to placebo, active nicotine spray significantly decreased reaction time on the Conner's CPT and improved scores on a measure purported to reflect spatial working memory on a dot task. There were trends for the increased number of hits and decreased number of errors in pre-post comparisons on the CPT task in the active nicotine session. There were no effects of active nicotine nasal spray on verbal memory. Our results suggest that nicotine may modestly enhance attention and spatial working memory in schizophrenic patients who are cigarette smokers and have been abstinent overnight.

Effects of olanzapine and risperidone on lipid metabolism in chronic schizophrenic patients with long-term antipsychotic treatment: a randomized five month study.

OBJECTIVE: Metabolic syndrome and elevated lipids, related to cardiovascular risk factors, are more prevalent in schizophrenia and there has been much debate about the extent to which specific antipsychotics contribute more to the increased risk of developing hyperlipidemia and metabolic syndrome. Most studies have concentrated on fasting levels in patients recently started on medication. Randomized prospective studies of metabolic effects of 2nd generation antipsychotics using both fasting measures and provocative tests may provide results that are more informative. We present results of a randomized prospective study of lipid metabolism and metabolic syndrome in chronic schizophrenic patients using both fasting and post-prandial lipid measures. METHOD: Hospitalized patients with chronic schizophrenia, most of whom had been treated with multiple antipsychotics in the past, were randomly assigned to treatment with a single antipsychotic, olanzapine or risperidone, for a period of 5 months. At baseline and every treatment month thereafter, fasting levels of lipids, free fatty acid (FFA) and leptin were assessed. At baseline and end of month 2 of treatment patients had a fatty meal test (FMT) in which postprandial lipids were measured at several time points before and after meal ingestion. Weight was assessed monthly and waist measures were taken at baseline and month 5. Data was analyzed on 23 patients randomized to risperidone and 23 patients randomized to olanzapine. RESULTS: Overall, there were no differential drug effects on any fasting lipid measure and fasting triglycerides did not increase in olanzapine treated patients after 5 months of treatment. However, at 2 months of drug treatment the FMT revealed a significantly greater increase in triglycerides, and very low density (VLDL) cholesterol and triglycerides, in olanzapine compared to risperidone patients (Ps=.05-.01). There was no difference between treatments with olanzapine vs. risperidone on development of metabolic syndrome during the 5 month treatment period. CONCLUSIONS: Chronic schizophrenic patients treated for years with first and second generation antipsychotics may have developed tolerance to the effects of olanzapine on increasing fasting triglycerides and other lipids, but some underlying metabolic abnormalities may be revealed in postprandial tests of lipid metabolism. These findings suggest that the development of standardized tests and criteria for measurement of postprandial triglycerides and related lipid levels, in addition to fasting levels, may be helpful in identifying metabolic effects of olanzapine and other second generation antipsychotics in chronically treated schizophrenics. In some reports postprandial increases in triglycerides have been identified as important risk factors for cardiovascular disease, but the actual differential consequences of these lipid metabolic differences for development of atherosclerosis and cardiovascular disease in patients treated with different antipsychotics need more objective outcome measures to determine and quantify cardiovascular risk outcomes.

Effects of olanzapine and risperidone on glucose metabolism and insulin sensitivity in chronic schizophrenic patients with long-term antipsychotic treatment: a randomized 5-month study.

BACKGROUND: Comparisons of diabetic potential, glucose related metabolic levels, and insulin resistance between olanzapine and risperidone have produced variable results in cross-sectional and epidemiologic studies. Randomized prospective studies of metabolic effects during treatment with these drugs may provide results that are more informative. METHOD: Hospitalized patients with chronic schizophrenia (DSM-IV), most of whom had been treated with multiple antipsychotics in the past, were randomly assigned to treatment with a single antipsychotic, olanzapine or risperidone, for a period of 5 months. At baseline and every treatment month thereafter, fasting glucose, insulin, insulin-related metabolic measures, and prolactin were assessed, and an oral glucose tolerance test (OGTT) was performed during baseline and months 1, 2, and 5 of treatment. Weight was assessed monthly, and waist and hip measures were taken at baseline and month 5. Data were analyzed on 23 patients randomly assigned to risperidone and 23 patients randomly assigned to olanzapine. The study was conducted from February 2003 to August 2007. RESULTS: Most patients were overweight or obese at baseline (mean body mass index [BMI] = 29.4), but there were no differential drug effects on weight change and no differences between drug groups at the 5-month time point. There were no overall drug treatment differences in fasting glucose or glycohemoglobin or 2-hour glucose levels in OGTT and no differences between the two drug groups at the 5-month time point. There were no consistent drug treatment differences in the number of patients who developed borderline or diabetic glucose levels. Olanzapine-treated patients showed a significantly greater increase than risperidone-treated patients in a fasting measure of insulin resistance (P = .041), and olanzapine patients showed greater decreases in insulin sensitivity during OGTT (P = .023) compared to risperidone-treated patients. Olanzapine-treated patients had a significantly greater increase in 1-hour glucose and insulin levels during OGTT in subsequent months compared to baseline and greater increase in glucose and insulin area under the curve over time than the risperdone-treated patients. Prolactin levels decreased in olanzapine patients and increased in risperidone patients (P values approximately .02). There were no significant drug treatment differences in C-peptide levels or 2 indices proposed as measures of insulin secretion or beta-cell function (homeostasis model assessment of beta-cell function [HOMA-B], BIGTT-acute insulin response surrogate measure [BIGTT-AIR]). Changes in insulin resistance over time were not strongly related to changes in BMI or waist circumference during study drug treatment. CONCLUSIONS: The increase in insulin levels during olanzapine treatment may compensate for the increase in insulin resistance and serve to reduce fasting and postprandial glucose levels. This may contribute to the lack of differences between olanzapine and risperidone in indices of diabetic or prediabetic glucose levels or glycohemoglobin. How many years this compensatory mechanism will persist needs further investigation. Periodic OGTT tests measuring glucose and insulin levels would be helpful in assessing the status of beta-cell insulin reserve in patients treated with olanzapine and other second-generation antipsychotics and assessing an individual patient's risk for conversion to type 2 diabetes. TRIAL REGISTRATION: clinicaltrials.gov Identifier NCT00287820.

Clozapine, risperidone, olanzapine, and conventional antipsychotic drug effects on glucose, lipids, and leptin in schizophrenic patients.

Some reports have indicated increased rates of diabetes and increased prevalence of glucose and lipid abnormalities during treatment with second-generation antipsychotics, with most concern raised about clozapine and olanzapine. Most of the findings have come from case reports, retrospective examination of laboratory values, and analysis of health-care claims databases. This study investigated fasting levels of glucose, lipids, and leptin in a non-randomized, cross- sectional study of 210 patients, with schizophrenic or schizoaffective disorder, treated with a single antipsychotic medication - clozapine, risperidone, olanzapine, or a conventional antipsychotic. Glucose tolerance tests (GTT), with a 75-g glucose load, were preformed in a subset of patients. In this sample most mean fasting glucose and lipid levels were within the normal range and were not significantly different across the four drug treatment groups. Patients treated with clozapine and olanzapine had higher triglyceride levels than risperidone patients. In patients receiving a GTT, risperidone-treated patients had higher glucose levels at 1 h than patients treated with olanzapine, and there were more patients on risperidone who met American Diabetes Association glucose metabolic criteria for diagnosis of diabetes. Although there were no significant differences in age or body mass index among the four drug groups, we cannot rule out some potential biasing factors we did not assess which could potentially influence our results. These include unknown physician preference in drug selection based on their beliefs about the weight-inducing or diabetes potential of different antipsychotics, differences in visceral fat, and differences in patients' antipsychotic drug history.