The purpose of this study is to explore the tolerability, safety and treatment response of flexibly dosed paliperidone ER in patients with schizophrenia who are admitted for an acute exacerbation of their disease.

This trial is an open-label, single arm, multicenter 6-week study which is aimed to explore tolerability, safety and effectiveness of flexibly dosed paliperidone ER in patients with schizophrenia who are admitted for an acute exacerbation of their disease. Hospitalization is mandatory for the first 7 days of the study. Patients who complete this 6-week study, responded and would like to continue treatment, will receive paliperidone ER, during an extension phase. This extension phase will last until the drug is approved and reimbursed in the respective country, or earlier, in case the sponsor would decide to stop the development and/or the registration of the product. In any case, the extension phase will last no longer than 12 months after the last subject has completed the 6-week core treatment phase of the study.

The primary aim of this study is to explore the treatment response to flexible doses of extended-release (ER) paliperidone in acutely exacerbated patients with schizophrenia. Response is defined as a decrease of at least 30% in total Positive and Negative Syndrome Scale (PANSS) score from baseline to endpoint.

The secondary objectives are to explore effectiveness, tolerability, safety, disease severity, functioning, and treatment satisfaction through the following.

Assessing the effectiveness on psychotic symptoms by Positive and Negative Syndrome Scale [PANSS] total score and subscores, the proportion of subjects improving >= 20%, >= 40% and >= 50% in total PANSS from baseline to endpoint and exploring the onset of efficacy of flexible doses of paliperidone ER (as measured by individual subject's change in total PANSS score between study visits).

Evaluation of the disease severity by Clinical Global Impression-Severity Scale [CGI-S], the personal and social functioning by Personal and Social Performance Scale [PSP], the quality of sleep and daytime drowsiness by a 11-point categorical evaluation scale and patients' treatment satisfaction by a 5-point categorical evaluation scale; Assessing the safety and tolerability for extrapyramidal symptoms by Abnormal Involuntary Movement Scale [AIMS]; Simpson-Angus Extrapyramidal Symptoms Rating Scale [SAS], and Barnes Akathisia Rating Scale [BARS]) and for side effect profiles by means of physical examination, body weight, vital signs and adverse events (AEs).

In general, the recommended paliperidone ER dose will be 6 mg once daily. Some patients may benefit from higher or lower doses in the recommended range of 3 to 12 mg once daily. Patients from any oral antipsychotic medication can be transitioned to an effective dose of paliperidone ER without the need for titration. There will be 4 dosage levels of paliperidone ER (3, 6, 9, and 12 mg). Throughout the study flexible dosing in a range of 3 to 12 mg/day may be used. Adjustment of the dosage will be done at the investigators' discretion, based on the individual patient's clinical response to and tolerability of the study drug. Patients who complete this 6-week core study and would like to continue will be eligible to be enrolled in an extension phase until paliperidone ER is available.

Inclusion Criteria:

• Patient meets the DSM-IV criteria for schizophrenia
• Patient must be experiencing an acute schizophrenic episode, with a PANSS total score at baseline of at least 70
• Patient must be admitted to hospital for treatment of the acute schizophrenic episode and must agree for voluntary hospitalization for at least the first 7 days of the study
• 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. Female patients of child-bearing potential must have a negative urine pregnancy test at screening.

Exclusion Criteria:

• First antipsychotic treatment ever
• On clozapine or a long-acting injectable antipsychotic during the last 3 months
• 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)
• Known clinically relevant abnormal laboratory values or ECG
• - History or current symptoms of tardive dyskinesia
• - History of neuroleptic malignant syndrome
• Judged to be at high risk for or presence of violence or self-harm
• Pregnant or breast-feeding female
• Have received an experimental drug or used an experimental medical device within 30 days before the planned start of treatment
• Patients with a narrowing or blockage of their gastro-intestinal tract
• Inability to swallow the study medication whole with the aid of water (subjects may not chew, divide, dissolve, or crush the study medication, as this may affect the release profile)
• Patients with current or known history (over the past 6 months) of substance dependence according to DSM-IV Criteria
• Employees of the investigator or study center, persons with direct involvement in the proposed study or other studies under the direction of that investigator or study center, or family members of the employees or the investigator
• Known hypersensitivity to paliperidone ER or risperidone.