PM480. Early schizophrenia patients treated with once-monthly paliperidone palmitate over a 12-month period - A Retrospective Observational Study

Background: Repeated administration of amphetamine elicits a progressive enhancement in behavioral and subjective responses to the drug and an increase in amphetamine-induced dopamine release. This enhancement is called sensitization and is able to induce changes in the response of the brain dopamine system to amphetamines mimicking certain aspects of dopaminergic dysfunction in schizophrenia. Objectives: We are conducting experiments using positron emission tomography (PET) and the D2/3 receptor agonist radioligand [11C]-(+)-PHNO, which is currently the optimal method for studying fluctuations in extracellular dopamine in the living human brain. Our primary objective is to compare the amphetamine-sensitized state in healthy controls to the amphetamine-response in schizophrenia on a neurochemical and behavioral level. Amphetamine-induced dopamine release is partly controlled by inhibitory action of D3 receptors. Studies using D3-selective compounds have shown that a large proportion of [11C]-(+)-PHNO binding in brainstem dopaminergic areas is to D3 receptors. Amphetamineinduced dopamine release will be analyzed on a network level for studying the role of D3 receptors in the response to amphetamine. Methods: Patients with first-episode schizophrenia and healthy subjects undergo two [11C]-(+)-PHNO PET scans, one drug-naïve, the other one after a small dose of oral d-amphetamine. Healthy subjects are sensitized with four doses of d-amphetamine before undergoing another scan. The subjective and neurochemical amphetamine-response in schizophrenia is then compared to the response in drug-naïve and sensitized healthy individuals by repeated ratings and by analyzing changes in binding potential values. Results: Our preliminary results show clear behavioral and neurochemical sensitization after repeated d-amphetamine in healthy subjects. Results in patients with schizophrenia are currently being analyzed. Conclusions: [11C]-(+)-PHNO PET is a suitable tool for studying amphetamine actions and the amphetamine-sensitized state. Analysis of [11C]-(+)-PHNO binding in subdivisions of the dopamine system will help elucidating similarities and differences between the amphetamine-sensitized state and ‘natural’ amphetamine-sensitization in schizophrenia. PM479 Clinical and Functional Response to Paliperidone Palmitate in Early Schizophrenia – A Retrospective Observational Study in Newly Diagnosed Patients Treated Over a 12-Month Period Andreas Schreiner1, Paul Bergmans2, Pierre Cherubin3, Ludger Hargarter1 1Janssen Cilag GmbH, Germany, 2Janssen Cilag Benelux, Netherlands, Abstract Introduction: Data on clinical outcomes with long-acting antipsychotic treatment in young, newly diagnosed patients with schizophrenia is sparse. OBJECTIVES: To explore hospitalization, drug utilization and clinical outcomes from medical records of newly diagnosed schizophrenia patients during first 12 months of treatment with once-monthly paliperidone palmitate (PP). Methods: International, multicenter, retrospective, observational study. Outcomes presented: baseline (BL) characteristics and demographics, clinically relevant improvements in disease severity (ie ≥20% decrease in PANSS or BPRS total score or CGI-S Change≥-2 or CGI-C≥3, with no score showing worsening) and clinically relevant functional improvement (ie change in PSP total score≥+7 points or change in GAF total score≥+20 points, with no score showing worsening) from BL to last-observationcarried-forward endpoint (LOCF-EP) within 12-month documentation period, mean mode PP dose and adverse drug reactions. Results: 84 patients analyzed: 69% male, mean age at initiation of PP was 24.1(SD2.7) years, Mean BL weight was 78.7(SD16.0)kg and 80.0(SD14.7)kg at LOCF-EP, with a mean change of 1.2(SD3.9) kg; mean time from first psychotic episode to initiation of PP was 5.5(SD3.3) months. At LOCF-EP 86.6% achieved a clinically relevant improvement (71/84, Kaplan-Meier median time from initiation of PP: 52.4 days). 63.4% achieved a clinically relevant functional improvement (52/84, Kaplan-Meier median time from initiation of PP: 53.1 days). PP mean mode maintenance dose was 96.4(SD19.8) mg. ADRs reported in ≥5% of patients were weight increase 9.1% and hyperprolactinemia 5.7%. Conclusions: Treatment with once-monthly PP was well tolerated and associated with clinically relevant improvements in disease severity and functioning in young, newly diagnosed schizophrenia patients.Introduction: Data on clinical outcomes with long-acting antipsychotic treatment in young, newly diagnosed patients with schizophrenia is sparse. OBJECTIVES: To explore hospitalization, drug utilization and clinical outcomes from medical records of newly diagnosed schizophrenia patients during first 12 months of treatment with once-monthly paliperidone palmitate (PP). Methods: International, multicenter, retrospective, observational study. Outcomes presented: baseline (BL) characteristics and demographics, clinically relevant improvements in disease severity (ie ≥20% decrease in PANSS or BPRS total score or CGI-S Change≥-2 or CGI-C≥3, with no score showing worsening) and clinically relevant functional improvement (ie change in PSP total score≥+7 points or change in GAF total score≥+20 points, with no score showing worsening) from BL to last-observationcarried-forward endpoint (LOCF-EP) within 12-month documentation period, mean mode PP dose and adverse drug reactions. Results: 84 patients analyzed: 69% male, mean age at initiation of PP was 24.1(SD2.7) years, Mean BL weight was 78.7(SD16.0)kg and 80.0(SD14.7)kg at LOCF-EP, with a mean change of 1.2(SD3.9) kg; mean time from first psychotic episode to initiation of PP was 5.5(SD3.3) months. At LOCF-EP 86.6% achieved a clinically relevant improvement (71/84, Kaplan-Meier median time from initiation of PP: 52.4 days). 63.4% achieved a clinically relevant functional improvement (52/84, Kaplan-Meier median time from initiation of PP: 53.1 days). PP mean mode maintenance dose was 96.4(SD19.8) mg. ADRs reported in ≥5% of patients were weight increase 9.1% and hyperprolactinemia 5.7%. Conclusions: Treatment with once-monthly PP was well tolerated and associated with clinically relevant improvements in disease severity and functioning in young, newly diagnosed schizophrenia patients. PM480 Early schizophrenia patients treated with oncemonthly paliperidone palmitate over a 12-month period A Retrospective Observational Study Andreas Schreiner1, Paul Bergmans2, Pierre Cherubin3, Ludger Hargarter1 1Janssen Cilag GmbH, Germany, 2Janssen Cilag Benelux, Netherlands, Abstract Introduction: Little is known about patient characteristics and rehospitalization in newly diagnosed patients with schizophrenia treated with long-acting antipsychotics. Objectives: To retrospectively explore hospitalizations, drug utilization and clinical outcomes from medical records of young, newly diagnosed schizophrenia patients during the first 12 months of treatment with once-monthly paliperidone palmitate (PP)Introduction: Little is known about patient characteristics and rehospitalization in newly diagnosed patients with schizophrenia treated with long-acting antipsychotics. Objectives: To retrospectively explore hospitalizations, drug utilization and clinical outcomes from medical records of young, newly diagnosed schizophrenia patients during the first 12 months of treatment with once-monthly paliperidone palmitate (PP)