• The primary objective is to compare paliperidone ER and olanzapine regarding change in the triglyceride to high density lipoprotein ratio (TG:HDL ratio).
  

• Secondary objectives are to evaluate additional metabolic endpoints and to demonstrate non-inferiority of paliperidone ER versus olanzapine in efficacy as measured by Positive and Negative Syndrome Scale (PANSS).
  

This is a prospective randomized (study medication is assigned by change) open-label parallel-group multicenter 6 month study which is aimed to compare the metabolic effects of paliperidone ER and olanzapine in patients with schizophrenia using the 'triglyceride - high density lipoprotein' ratio as the primary parameter. Secondary objectives include evaluation of additional metabolic endpoints and demonstration of non-inferiority of paliperidone ER versus olanzapine in efficacy as measured by Positive and Negative Syndrome Scale (PANSS). Patients previously treated with any oral antipsychotic except those treated with paliperidone ER, olanzapine or clozapine during the last 6 months, can be enrolled and will be treated with paliperidone ER (6 to 9 mg/day) or olanzapine (10 to 15 mg/day). Patients will be stratified according to the metabolic effects of their previous antipsychotic medication (weight neutral vs. not neutral). Throughout the study flexible dosing is allowed based on the investigator's discretion. A study treatment period of 6 months is planned for all patients. Anticholinergic medication may continue up to four weeks and should then be tapered off at the discretion of the investigator. Approximately 456 adult patients (228 in each treatment group) will participate in this study. Efficacy will be assessed with the following measures: PANSS (total score and subscale scores), CGI-S, Self-rated health status Survey SF-36, and Sleep and daytime drowsiness evaluation scale.The Metabolic endpoints will be assessed with the following: TG/HDL ratio (for this primary evaluation, plasma fasting TG and HDL concentrations will be measured), fasting plasma insulin and fasting plasma glucose for the homeostatic model assessment of b-cell function (HOMA2-%B) and homeostatic model assessment of insulin sensitivity (HOMA-%S), plasma glucose and insulin concentrations before and after a 75 gram oral glucose tolerance test to asses insulin sensitivity and changes in insulin secretion, fasting HDL, TG, and glucose levels for the determination of new onset or presence of metabolic syndrome during treatment according to NCEP/ATP III criteria, weight, Body-Mass-Index and waist circumference for the determination of new onset or presence of metabolic syndrome during treatment according to NCEP/ATP III criteria. All patients who receive trial medication (paliperidone ER or olanzapine) at least once will be included in the analysis of the demographic and baseline characteristic data. This is the intent-to-treat analysis set. All patients who receive trial medication at least once and provide at least 1 post-baseline efficacy measurement will be included in efficacy data analyses. This is the intent-to-treat analysis set for efficacy. All patients who receive trial medication at least once and provide any post-baseline information will be included in safety data analyses. This is the intent-to-treat analysis set for safety. If there is a substantial number of protocol violators (e.g., more than 10%), an additional per-protocol analysis may be performed.

2 dosage levels of paliperidone ER (6 or 9mg per day) and 2 of olanzapine (10 and 15mg per day) are available to the patients. Throughout the study flexible dosing is allowed based on the investigator's discretion. Study medication is to be taken in the morning orally, with water. A study treatment period of 6 months is planned for all patients.

Inclusion Criteria:

• Patient meets the DSM-IV criteria for schizophrenia
• Patient has a PANSS total score at screening of 60 to 100, inclusive
• Patient must, in the opinion of the investigator, benefit from treatment with paliperidone ER or olanzapine
• Patients on lipid-lowering therapy must be on a stable dose for at least 4 weeks for statins, niacin, ezetimibe and resins or for at least 12 weeks for fibrates
• Female patients must be postmenopausal (for at least 1 year), surgically sterile, abstinent, or, if sexually active, be practicing and effective method of birth control (e.g. prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before entry and throughout the study
• Women of child-bearing potential must have a negative urine pregnancy test at screening
• Patient is healthy on the basis of a physical examination and vital signs at screening

Exclusion Criteria:

• Patient has previously been treated with paliperidone ER, olanzapine, or clozapine within the past 6 months or has never been treated with an antipsychotic before
• Treatment with a depot antipsychotic within the past 3 months
• Treatment with a mood stabilizer or a recently initiated antidepressant (<= 3 months)
• Patient has abnormal fasting plasma glucose (> 126 mg/dL) or fasting triglycerides (TG) levels (> 400 mg/dL) at screening
• Relevant history of any significant and/or unstable cardiovascular, respiratory, neurologic (including seizures or significant cerebrovascular), renal, hepatic, endocrine, or immunologic diseases, including recent or present clinically relevant laboratory abnormalities (as deemed by the investigator)
• History or current symptoms of tardive dyskinesia
• History of neuroleptic malignant syndrome
• Pregnant or breast-feeding female