A double-blind, placebo-controlled trial of sibutramine for olanzapine-associated weight gain.

OBJECTIVE: Weight gain is commonly observed with olanzapine treatment and can increase the risk for obesity, cardiovascular disease, hypertension, and diabetes mellitus. This study examined the effectiveness of sibutramine, an approved weight loss agent, in overweight and obese subjects taking olanzapine for schizophrenia or schizoaffective disorder. METHOD: Each subject had a DSM-IV diagnosis of schizophrenia or schizoaffective disorder, had been taking a stable dose of olanzapine for at least 4 months, and had a body mass index of >/=30 kg/m(2) or >/=27 kg/m(2) plus at least one cardiovascular risk factor. In a 12-week double-blind, randomized, placebo-controlled study, 37 subjects received placebo or sibutramine (up to 15 mg/day). For the first 8 weeks all subjects participated in weekly group sessions focused on nutrition and behavioral modification. RESULTS: The sibutramine and placebo groups had no significant baseline differences on age, gender, education, ethnicity, diagnosis, weight, body mass index, and blood pressure. At week 12 the sibutramine group had significantly greater losses than the placebo group in weight (mean=8.3 lb, SD=2.4, versus mean=1.8 lb, SD=1.6), waist circumference, body mass index, and hemoglobin A(1c). There were no significant differences on most side effects, although the sibutramine group exhibited a mean increase in systolic blood pressure of 2.1 mm Hg (SD=8.5), and anticholinergic side effects and sleep disturbances were at least twice as common in the sibutramine group. CONCLUSIONS: Sibutramine was an effective and well-tolerated adjunct to behavior modification for weight loss in patients with schizophrenia and schizoaffective disorder being treated with olanzapine.

Clozapine, diabetes mellitus, hyperlipidemia, and cardiovascular risks and mortality: results of a 10-year naturalistic study.

OBJECTIVE: The goal of this 10-year naturalistic study was to examine, in clozapine-treated patients, the change in cardiovascular risk factors following clozapine initiation and the mortality estimates from cardiovascular disease. METHOD: Data were collected from medical records from January 1992 to December 2003 and included age, gender, race, diagnosis, family history of diabetes, and age at clozapine initiation for clozapine-treated patients with schizophrenia or schizoaffective disorder (DSM-IV criteria). Clozapine dosage and laboratory results were recorded at 12-month intervals. RESULTS: At the time of clozapine initiation, the mean +/-?SD age of the 96 patients studied was 36.5 +/- 7.9 years; 28% (N = 27) were women. The Kaplan-Meier estimate for 10-year mortality from cardiovascular disease was 9%. African American and Hispanic American patients exhibited elevated risk of cardiovascular disease-related mortality (odds ratio [OR] = 7.2, p = .09; OR = 11.3, p = .04, respectively) compared to white patients. Body mass index (BMI) significantly increased the odds ratio of mortality (OR = 1.2, p < .01). The Kaplan-Meier estimate for new-onset diabetes mellitus was approximately 43%, and Hispanic American (OR = 4.3, p = .027) and African American (OR = 11.5, p = .0001) patients showed elevated risks of developing diabetes mellitus compared to white patients. Additionally, BMI (OR = 1.11, p = .0006), total cholesterol level (OR = 1.006, p = .04), and serum triglyceride level (OR = 1.002, p = .04) modestly increased the odds ratio for the development of diabetes mellitus. CONCLUSIONS: These results support the hypothesis that clozapine-treated patients appear to be at risk for death from cardiovascular disease secondary to clozapine-associated medical disorders such as obesity, diabetes, hypertension, and hyperlipidemia.

Elevated hemoglobin A1c as a possible indicator of diabetes mellitus and diabetic ketoacidosis in schizophrenia patients receiving atypical antipsychotics.

OBJECTIVE: We conducted a retrospective epidemiologic study assessing the incidence of new-onset diabetes mellitus presenting as diabetic ketoacidosis in patients with schizophrenic disorders (ICD-9 295.0-295.9; referred to as "schizophrenia patients" hereafter) treated with atypical antipsychotic agents. METHOD: The identification of patients and the review of records were achieved by using an electronic database linking administrative and clinical laboratory data between January 1, 1995, and December 31, 2001. The main outcome measure was the incidence of diabetic ketoacidosis or hyperosmolar hyperglycemic syndrome per 10,000 patient years in patients with new-onset or existing diabetes mellitus. We also determined the incidence of diabetic ketoacidosis associated with the use of atypical antipsychotics and calculated the mean hemoglobin A1c (HbA1c) level for all patients. RESULTS: During the 7-year period, 18.4% of schizophrenia patients were diagnosed with diabetes mellitus, compared with 6.6% in the general hospital population (p < .001). After chart review, 23 schizophrenia patients were identified with diabetic ketoacidosis: 11 had diabetes presenting as diabetic ketoacidosis, 8 had diabetic ketoacidosis with known diabetes mellitus, 2 had new-onset diabetes mellitus-hyperosmolar hyperglycemic syndrome, and 2 had hyperosmolar hyperglycemic syndrome with known diabetes mellitus. The incidence of diabetes presenting as diabetic ketoacidosis in schizophrenia patients was more than 10-fold higher than that reported in the general population: 14.93 per 10,000 patient years in schizophrenia patients versus 1.4 per 10,000 patient years in the general population (p < .000001) and versus the 1.98 per 10,000 patient years in the general hospital population (p < .000001). The incidence of diabetic ketoacidosis for each of atypical antipsychotic drugs over the 7-year period was as follows: clozapine, 2.2%; olanzapine, 0.8%; and risperidone, 0.2% (no incidence with ziprasidone or quetiapine). Of the 11 patients with diabetes presenting as diabetic ketoacidosis, the mean HbA1c level at admission was 13.3% +/- 1.9% (10.4%-16.9%). CONCLUSIONS: The incidence of diabetes mellitus presenting as diabetic ketoacidosis in schizophrenia patients is higher than in the general hospital population and differs across atypical antipsychotic agents. Elevated HgbA1c levels observed suggests that patients had undiagnosed diabetes mellitus for at least several weeks before the diabetic ketoacidosis episode.

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.

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.