Dana D. Nguyen

An exploratory open-label trial of aripiprazole as an adjuvant to clozapine therapy in chronic schizophrenia

Objective:  We conducted this 6‐week open‐label trial to examine the effects of adjunctive aripiprazole in clozapine‐treated subjects on weight, lipid and glucose metabolism, as well as positive and negative symptoms of schizophrenia.

Dietary Intake Profile of Patients with Schizophrenia

BACKGROUND The increasing prevalence of overweight and obesity has become a priority public health issue in the United States. Forty to 62% of people with schizophrenia are obese or overweight (1, 2). High morbidity and mortality in schizophrenia may be attributed to an unhealthy lifestyle such as poor diet, lack of exercise, smoking, and substance abuse (3). Obesity is associated with greater risk of developing hypertension, type 2 diabetes, coronary heart disease, stroke, death, and reduced quality of life compared with that found in the general population (4, 5). We performed a cross-sectional study evaluating the dietary intake of patients with schizophrenia or schizoaffective disorder treated with atypical antipsychotic agents. METHODS Dietary intake of 88 patients from an urban community mental health clinic was measured using a four-day dietary record. Nutritional variables included total energy intake, fat, protein, carbohydrate, cholesterol, fiber, sucrose, folate, calcium, sodium, zinc, alcohol and caffeine. Data were compared to the general population using data matched for age, gender, and ethnicity from the National Health and Nutrition Examination Survey (NHANES), 1999-2000. RESULTS The Body Mass Index (BMI) of the schizophrenia group (M = 31.3, SD = 12.67) was significantly greater than the NHANES group (M = 28.3, SD = 6.62) (p = .001). The schizophrenia group consumed significantly fewer calories, carbohydrate, protein, total fat, saturated fat, monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), fiber, folate, sodium and alcohol and significantly more caffeine than the NHANES group. CONCLUSIONS The findings may suggest that obesity in schizophrenia patients is not solely related to food consumption, but perhaps other effects including medication side effects and reduced physical activity. Education and interventions for the schizophrenia population should focus more on overall lifestyle factors such as physical activity and healthy food choices.

A double‐blind, placebo‐controlled trial of sibutramine for clozapine‐associated weight gain

Objective:  This study sought to examine the effectiveness of sibutramine, a weight loss agent, on clozapine‐associated weight gain.

Posttraumatic stress disorder, cognitive function and quality of life in patients with schizophrenia

The purpose of the present study was to assess posttraumatic stress disorder (PTSD), cognitive function, and quality of life in patients with schizophrenia who had a self-reported history of trauma exposure. Outpatients diagnosed with schizophrenia or schizoaffective disorder were referred to the study. Each patient was assessed with the Positive and Negative Syndrome Scale (PANSS), the Harvard Trauma Questionnaire (HTQ), a cognitive assessment battery, Heinrichs Quality of Life Scale (QLS), and the Behavior and Symptom Identification Scale (BASIS). Eighty-seven subjects who reported experiencing at least one traumatic event were included in the study. Fifteen of 87 (17%) met the DSM-IV criteria for PTSD. The PTSD group had significantly worse overall cognitive performance than the non-PTSD group, especially in the domains of attention, working memory and executive function. In addition, the PTSD group showed significantly worse self-rated quality of life as measured by the BASIS total score. The development of PTSD is associated with poor cognitive function and subjectively, but not objectively, rated low quality of life in patients with schizophrenia. Evaluating PTSD in patients with schizophrenia could have important implications from both clinical and research perspectives.

Homocysteine levels and glucose metabolism in non-obese, non-diabetic chronic schizophrenia

Objective:  We studied a sample of schizophrenia out‐patients to test the hypotheses that serum homocysteine concentrations would correlate positively with measures of glucose metabolism.

Modafinil-associated weight loss in a clozapine-treated schizoaffective disorder patient.

BACKGROUND We report a case of weight loss associated with modafinil-initiation in a clozapine-treated man with schizoaffective disorder. METHODS To report the impact of modafinil, a wake promoting agent that lacks the unwanted side affects brought on by many psychostimulants, on weight in a clozapine-treated patient. RESULTS Modafinil was initiated, and over the course of 1 year, Mr. B. experienced a weight loss of 40 lbs (from 280 lbs to 240 lbs) and a reduction in body mass index (BMI) of 5.08 Kg/m2 (from 35.52 Kg/m2 to 30.44 Kg/m2). After 3 years on the combination of clozapine and modafinil, his weight stabilized at 230 lbs (BMI = 29.59 Kg/m2). A 30-lb weight gain over a 6-month period occurred following discontinuation of modafinil. Reinstitution of modafinil resulted in a 10-lb. weight loss over a 6-week period. CONCLUSIONS Modafinil treatment resulted in a significant weight loss in this patient, possibly due to reducing clozapine-associated fatigue. Randomized placebo-controlled trials are necessary to evaluate the safety and efficacy of modafinilfor clozapine-associated weight gain.

Higher Fasting Serum Insulin Is Associated with Increased Resting Energy Expenditure in Nondiabetic Schizophrenia Patients

BACKGROUND Insulin has emerged as an important determinant of food intake, energy expenditure, and weight control. This study examined the relationship between fasting serum insulin level and resting energy expenditure (REE) in a cross-sectional sample of nondiabetic schizophrenia patients. METHODS Subjects were recruited from an urban community mental health clinic. Each subject underwent a series of anthropometric measures and an indirect calorimetry measure. A fasting blood sample was taken for plasma glucose, serum insulin, and lipid profile. RESULTS Seventy-one subjects (54 male, 17 female) were included in the study. There was a significant positive relationship between REE and fasting serum insulin level (r = .39, p = .001). Stepwise multiple regression analysis was performed with various characteristics such as age, race, antipsychotic agent used, fat-free mass, BMI, waist circumference, waist-hip ratio, physical activity level, and fasting serum insulin as candidate predictors for REE. Only fat-free mass and insulin were able to enter into the regression model, which indicates that higher fat-free mass and higher fasting serum insulin level predict increased REE. CONCLUSIONS A higher fasting serum insulin level is associated with an increased REE, which may prevent further weight gain in nondiabetic patients with schizophrenia.

Waist circumference does not predict insulin resistance in African American schizophrenia patients

The objective of the study was to determine whether race plays a role in the relationship between waist circumference and insulin resistance in an African American and white sample of subjects with schizophrenia. A cross-sectional comparison was conducted to determine the relationship between waist circumference and insulin resistance in 55 subjects treated with antipsychotic medication. Each subject underwent an anthropometric assessment of waist and hip circumference, height, weight and body mass index. Laboratory assays were performed to assess insulin resistance by the homeostasis model assessment for insulin resistance (HOMA-IR). Data for fifty-five subjects are reported: white/Caucasian (n=38) and African American (n=17). Mean waist circumference was higher in whites (98 cm±11 cm) compared with African Americans (94 cm±11 cm) but not statistically significant (p=0.181). There was no correlation between waist circumference and insulin resistance calculated by HOMA-IR in the African American subject sample (r=0.05, p=0.853). There was a statistically significant positive correlation between waist circumference and insulin resistance in the white subjects (r=0.66, p≤0.001). After controlling for demographic variables, white subjects had a statistically significant positive correlation between waist circumference and insulin resistance (r=0.623, p=0.00) while African American subjects did not (r=0.022, p=0.944). When age, gender and current antipsychotic agent are controlled for, multiple regression analysis show that waist circumference, race and their interaction term (waist circumference X race) all had significant contributions to the variance of HOMA-IR. Race appeared to be a significant modulator for the relationship between waist circumference and HOMA-IR. The study concludes that race is an important modulator for the relationship between waist circumference and insulin resistance. While waist circumference was an excellent predictor of insulin resistance for white schizophrenia subjects, it was not in the African American schizophrenia population. These findings suggest that predictors in the general population may not be applicable to African American schizophrenia patients receiving atypical antipsychotic medications.