Paliperidone Extended Release Versus Olanzapine in Treatment-Resistant Schizophrenia: A Randomized, Double-Blind, Multicenter Study.

PURPOSE: Paliperidone is an atypical antipsychotic as effective as other atypical antipsychotics for schizophrenia. However, few studies have explored the efficacy of paliperidone for treatment-resistant schizophrenia. This study aimed to compare the efficacy and safety of paliperidone extended release (ER) versus olanzapine in schizophrenia patients with either poor treatment response or intolerable adverse effects due to standardized antipsychotic therapy. METHODS: This 12-week randomized, double-blind, multicenter study compared the treatment efficacy on psychotic symptoms, cognitive functions, and tolerance between paliperidone ER (6-15 mg/d, n = 45) and olanzapine (10-30 mg/d, n = 41) in treatment-resistant or treatment-intolerant patients with schizophrenia. The severity of psychotic symptoms was evaluated by the Positive and Negative Syndrome Scale and the Clinical Global Impression Severity of Illness Scale. The cognitive functions were assessed by the MATRICS Consensus Cognitive Battery. In addition, the metabolic impacts were evaluated by weight gain and waist circumference. RESULTS: Patients with either paliperidone ER or olanzapine treatment showed apparent improvement in psychotic symptoms, without significant intergroup difference. Twelve-week paliperidone ER or olanzapine treatment did not improve the cognitive functions. Both paliperidone ER and olanzapine treatment caused significant increase in weight and waist circumference, and olanzapine had a greater impact on waist circumference than paliperidone ER. In addition, both drugs were well tolerated. CONCLUSIONS: Paliperidone ER could be a safe alternative for treatment-resistant schizophrenia.

Comparison and optimization of b value combinations for diffusion-weighted imaging in discriminating hepatic fibrosis.

INTRODUCTION AND OBJECTIVES: Diffusion-weighted imaging (DWI) has shown potential in characterizing hepatic fibrosis. However, there are no widely accepted apparent diffusion coefficient (ADC) values for the b value combination. This study aims to determine the optimal high and low b values of DWI to assess hepatic fibrosis in patients with chronic liver disease. MATERIALS AND METHODS: The prospective study included 81 patients with chronic liver disease and 21 healthy volunteers who underwent DWI, Magnetic resonance elastography (MRE), and liver biopsy. The ADC was calculated by twenty combinations of nine b values (0, 50, 100, 150, 200, 800, 1000, 1200, and 1500 s/mm2). RESULTS: All ADC values of the healthy volunteers were significantly higher than those of the hepatic fibrosis group (all P < 0.01). With the progression of hepatic fibrosis, ADC values significantly decreased in b value combinations (100 and 1000 s/mm2, 150 and 1200 s/mm2, 200 and 800 s/mm2, and 200 and 1000 s/mm2). ADC values derived from b values of both 200 and 800 s/mm2 and 200 and 1000 s/mm2 were found to be more discriminative for differentiating the stages of hepatic fibrosis. An excellent correlation was between the ADC200-1000 value and MRE shear stiffness (r = - 0.750, P < 0.001). CONCLUSION: DWI offers an alternative to MRE as a useful imaging marker for detecting and staging hepatic fibrosis. Clinically, ADC values for b values ranging from 200-800 s/mm2 to 200-1000 s/mm2 are recommended for the assessment of hepatic fibrosis.

A randomized, 12-week study of the effects of extended-release paliperidone (paliperidone ER) and olanzapine on metabolic profile, weight, insulin resistance, and ß-cell function in schizophrenic patients.

OBJECTIVE: To compare matched paliperidone-ER- and olanzapine-treated schizophrenic patients on measures of glucose and lipid metabolism. METHODS: Eighty hospitalized patients with schizophrenia (DSM-IV) were randomly assigned to treatment with paliperidone ER or olanzapine for a period of 12 weeks. At baseline and every 4 weeks, we assessed weight, subcutaneous fat, waist and hip circumferences, fasting glucose, insulin, glycohemoglobin A1, cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, and prolactin. We also assessed at every time point body mass index (BMI), homeostasis insulin resistance (HOMA-IR), and homeostasis ß-cell function (HOMA-B). RESULTS: Thirty-three patients randomly assigned to paliperidone ER and 23 patients randomly assigned to olanzapine groups completed the entire 12-week treatment. Within-group analyses showed that fasting measures in both groups increased for weight, BMI, waist circumferences, hip circumference, subcutaneous fat, cholesterol, triglycerides, and prolactin. In contrast, fasting glucose, LDL, and HOMA-B increased during treatment only in the olanzapine group. We also detected significantly different serum prolactin levels at all time point between the paliperidone ER- and olanzapine-treated groups, as well as a statistical trend for HOMA-B to increase more in the olanzapine compared to paliperidone-ER group over the 12 weeks of the trial. We did not detect, however, differential drug effects over the 12 weeks of the trial on fasting measures of BMI, glucose, glycohemoglobin A1, insulin, HDL, LDL, cholesterol, triglyceride, or HOMA-IR. CONCLUSION: This study reinforces the necessity of regularly monitoring metabolic parameters in patients with schizophrenia taking atypical antipsychotics, including paliperidone ER.