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OBJECTIVE To examine the efficacy and safety of paliperidone palmitate once-monthly (PP1M) versus oral antipsychotics (OAPs) in Black/African American patients with schizophrenia and a history of criminal justice system involvement. METHODS This was a post hoc analysis of a 15-month prospective, randomized, open-label, parallel-group, multicenter US study conducted from May 2010 to December 2013 that examined a subpopulation of Black/African American patients with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria). The primary objective was to compare time to first treatment failure in patients treated with PP1M versus OAPs. Secondary objectives were to compare time to first institutionalization (psychiatric hospitalization or arrest/incarceration) and mean number of treatment failure events and institutionalizations over 15 months in PP1M-treated and OAP-treated patients. RESULTS The intention-to-treat population included 275 Black/African American patients (PP1M, n = 145; OAPs, n = 130). Median time to first treatment failure was not reached for PP1M-treated patients and was 270 days for OAP-treated patients; hazard ratio (HR) was 1.39 (95% CI, 0.97-1.99; P = .075). Median time to first institutionalization was not reached for PP1M-treated patients and was 304 days for OAP-treated patients; HR was 1.49 (95% CI, 1.01-2.19; P = .043). Mean numbers of treatment failure events and institutionalizations were lower with PP1M than OAPs. The safety profile of PP1M was consistent with that of previous PP1M studies. CONCLUSIONS In a Black/African American subpopulation of patients with schizophrenia and prior criminal justice system involvement, PP1M reduced the number of treatment failures, thereby reducing the number of psychiatric hospitalizations and/or arrests/incarcerations compared with daily OAPs. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01157351.

Objective: Insulin resistance, changes in lipid parameters, and cardiometabolic adverse events have been reported in some patients during clinical trials of antipsychotic agents. The present study examined whether the triglyceride/high-density lipoprotein (HDL) ratio can be used as a better surrogate than other conventional lipid measures (low-density lipoprotein [LDL], HDL, triglyceride) in predicting insulin resistance and LDL particle size in nondiabetic patients with schizophrenia. Method: Outpatients 18 to 75 years old diagnosed with schizophrenia or schizoaffective disorder (DSM-IV criteria) and receiving olanzapine, risperidone, or typical antipsychotics participated in a multicenter, cross-sectional study. Fasting blood samples were obtained to determine the levels of glucose, insulin, lipids, and lipid particle size. The study was conducted from July 2001 to March 2002. Results: In the sample of 206 patients, significant correlations were found between various lipid measures (LDL, HDL, triglyceride, and triglyceride/ HDL ratio) and the homeostasis model of assessment of insulin resistance (P< .05). However, stepwise multiple regression analysis suggested that the triglyceride/HDL ratio is a stronger predictor of insulin resistance and of LDL particle size than other conventional lipoprotein measures after other potential confounding variables, including age, gender, race, family history of diabetes, body mass index, and antipsychotic agent, were taken into consideration (P < .001). Further, logistic regression analysis indicated that the triglyceride/ HDL ratio and male gender predict the existence of a small LDL particle size pattern (pattern B LDL phenotype), with a sensitivity of 75.9% and a specificity of 85.4%. Conclusions: The triglyceride/HDL ratio, a simple, readily available and inexpensive measure, can be a useful surrogate to identify those with insulin resistance as well as those with more atherogenic small LDL particles in nondiabetic patients with schizophrenia.

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.

Background Medical morbidity and mortality rates remain elevated in schizophrenia patients compared with the general population, in part due to potentially reversible medical risk factors. Psychiatrists should address this problem by adopting established strategies for prevention and intervention. Method The literature on modifiable medical risk factors relevant to individuals with schizophrenia and corresponding guidelines for prevention and treatment established by expert consensus panels were reviewed. Results Schizophrenia patients are at elevated risk for cardiovascular disease due to high rates of cigarette smoking and, increasingly, due to obesity, diabetes, and hypertriglyceridemia. Rates of human immunodeficiency virus infection and infectious hepatitis are also higher in schizophrenia patients. Interventions that have reduced medical morbidity in the general population can be adopted to reduce premature mortality in individuals with schizophrenia. Conclusions Patients with schizophrenia have high rates of potentially reversible medical morbidity. Implementation of practice guidelines for identifying and modifying risk factors could substantially improve the health of patients with schizophrenia.

Objective Clozapine has been linked to significant weight gain and increase in serum lipids and appears to negatively impact glucose metabolism. In this retrospective chart review study, we examine changes in systolic and diastolic blood pressure and treatment for hypertension in clozapine-treated patients. Method Data on demographics and systolic and diastolic blood pressure were examined for up to 5 years (September 1987 to September 1992) in 82 patients treated with clozapine. Rates of hypertension treatment in clozapine-treated patients were compared with patients receiving conventional antipsychotics (N = 56) and other atypical antipsychotic agents (N = 102). Results The mean age of the 82 patients at the time of clozapine initiation was 36.4 +/- 7.8 years, with 22 (27%) female, 75 (91%) white, 3 (4%) black, 3 (4%) Hispanic, and 1 (1%) Asian. The baseline weight was 175.5 +/- 34.0 lb (79.0 +/- 15.3 kg) and baseline body mass index was 26.9 +/- 5.0 kg/m(2). There was a significant increase in systolic blood pressure (p =.0004) and diastolic blood pressure (p =.0001). Overall, 22 patients (27%) received treatment for hypertension following clozapine initiation. Only 2 (4%) of 56 patients in the conventional antipsychotic group and 9 (9%) of 102 patients in the other atypical antipsychotic group (olanzapine, N = 6; risperidone, N = 3) received treatment for hypertension. Conclusion Our findings suggest that long-term clozapine treatment is associated with increased rates of hypertension, which may have a significant impact on medical morbidity and mortality.

Patients with schizophrenia have increased rates of morbidity and mortality due primarily to cardiovascular disease, compared with the general population. Case reports, case series, observational analytic epidemiologic studies, and randomized trials raise the possibility that some antipsychotic drugs add to this increased risk, likely due to drug-induced weight gain and associated metabolic abnormalities including hyperglycemia, diabetes mellitus, and dyslipidemia. This constella

Background: In our experience, many of our schizophrenic patients treated with clozapine request the newer atypical antipsychotic agents in order to eliminate the weekly blood monitoring. However, there are few guidelines available to clinicians interested in switching patients successfully treated with clozapine to olanzapine. Method: The goal of this study was to collect preliminary data on the safety, clinical effectiveness, and predictors of response of switching clozapine patients to olanzapine. In an open trial, 19 patients receiving clozapine were switched to olanzapine. Results: Eight (42%) of 19 patients were considered responders. Seven patients decompensated seriously enough to require hospitalization. All 7 of these patients were restabilized on clozapine treatment in the hospital, and olanzapine was discontinued. In an additional 4 patients, clinical status worsened, and clozapine doses were titrated upwards and olanzapine was slowly discontinued. Overall, mean total Brief Psychiatric Rating Scale (BPRS) scores increased significantly from baseline to final assessment (p = .02). Responders had been treated for a significantly shorter period of time with clozapine prior to the switch compared to nonresponders (p = .04) and were receiving a lower dose of clozapine (p = .05). The final olanzapine dose did not differ between responders and nonresponders. All responders have remained on olanzapine treatment and are stable. Conclusion: In this open trial, the crossover from clozapine to olanzapine was generally well tolerated and resulted in a successful transition for 8 of the 19 patients. However, mean scores on the total BPRS and negative symptom and depressive symptom subscales significantly increased. Caution must be taken in determining which patients may benefit from the switch to olanzapine because of the risk of decompensation and hospitalization. Because this was an open trial, these findings require replication in a controlled trial.

The proven efficacy of second-generation antipsychotics (SGA) has led many clinicians to switch patients from a conventional antipsychotic to an SGA. However, SGAs may be associated with weight gain, dyslipidemia, high blood pressure, and ultimately with cardiovascular disease, diabetes, and metabolic syndrome. Clinicians should be aware of patients' individual risk factors for developing these illnesses and should carefully screen for changes in weight, body mass index, waist size, or lipid levels that could be potentially harmful and increase the risk for a more serious illness.