Auditing Clinical Outcomes after Introducing Off-Licence Prescribing of Atypical Antipsychotic Melperone for Patients with Treatment Refractory Schizophrenia
Abstract:Aims and Method. To evaluate the practical utility of off-licence prescribing and clinical outcomes of treatment with atypical antipsychotic Melperone. Method: Prospective data collection on patient's clinical characteristics and outcomes. Results. 17 patients with a diagnosis of refractory schizophrenia were identified as suitable for off-license prescribing of Melperone and commenced treatment (13 were previously treated with Clozapine). Seven of those currently remain on Melperone (41%), and for six patents… Show more
“…A number of APDs have been classified as both typical and atypical APDs in separate studies. To recognize this, we have placed these drugs in a third group “typical/atypical” that includes sulpiride 60 – 62 , melperone 7 , 62 , 63 , loxapine 58 , 59 , 64 , molindone 65 – 67 , zotapine 7 , 61 , raclopride 68 , 69 , and thioridazine 62 , 66 , 70 . Domperidone is not an APD and is used to block D 2 receptors in the periphery Fig.…”
Atypical antipsychotic drugs (APDs) have been hypothesized to show reduced extrapyramidal side effects (EPS) due to their rapid dissociation from the dopamine D2 receptor. However, support for this hypothesis is limited to a relatively small number of observations made across several decades and under different experimental conditions. Here we show that association rates, but not dissociation rates, correlate with EPS. We measured the kinetic binding properties of a series of typical and atypical APDs in a novel time-resolved fluorescence resonance energy transfer assay, and correlated these properties with their EPS and prolactin-elevating liabilities at therapeutic doses. EPS are robustly predicted by a rebinding model that considers the microenvironment of postsynaptic D2 receptors and integrates association and dissociation rates to calculate the net rate of reversal of receptor blockade. Thus, optimizing binding kinetics at the D2 receptor may result in APDs with improved therapeutic profile.
“…A number of APDs have been classified as both typical and atypical APDs in separate studies. To recognize this, we have placed these drugs in a third group “typical/atypical” that includes sulpiride 60 – 62 , melperone 7 , 62 , 63 , loxapine 58 , 59 , 64 , molindone 65 – 67 , zotapine 7 , 61 , raclopride 68 , 69 , and thioridazine 62 , 66 , 70 . Domperidone is not an APD and is used to block D 2 receptors in the periphery Fig.…”
Atypical antipsychotic drugs (APDs) have been hypothesized to show reduced extrapyramidal side effects (EPS) due to their rapid dissociation from the dopamine D2 receptor. However, support for this hypothesis is limited to a relatively small number of observations made across several decades and under different experimental conditions. Here we show that association rates, but not dissociation rates, correlate with EPS. We measured the kinetic binding properties of a series of typical and atypical APDs in a novel time-resolved fluorescence resonance energy transfer assay, and correlated these properties with their EPS and prolactin-elevating liabilities at therapeutic doses. EPS are robustly predicted by a rebinding model that considers the microenvironment of postsynaptic D2 receptors and integrates association and dissociation rates to calculate the net rate of reversal of receptor blockade. Thus, optimizing binding kinetics at the D2 receptor may result in APDs with improved therapeutic profile.
“…Among these, melperone, a common antipsychotic drug that has been in clinical use for more than 50 years, is the best known case. 5 Itriglumide has been identified as cholecystokinin receptor CCK2 antagonist with nanomolar activity. Rottapharm is currently developing the drug for treatment of gastrointestinal disorders, 6 and it has successfully completed Phase I clinical trials and has passed to Phase II.…”
“…Reliability methods have been widely used in risk analysis of medical surgeries. Combine a fault tree with Markov models studied with data collected from a general hospital, to illustrate the operational process of the proposed method [3]. From the risk factors of drugs, risks that can easily arise in all aspects of clinical drug use were described and analyzed [4].…”
Pharmacovigilance and rational use of drugs, clinical application and evaluation, drug risk management is an important content of drug epidemiology. How to take advantage of Petri net monitoring Clinical Medication Safety in the hospital information system, obtain human reliability fault data, and using Petri model analysis identification of Pharmacovigilance and rational use of drugs, establishment rational use of medicines (RUM). Based on fault tree analysis (FTA) focus on analyze the medical staff human reliability about hospital clinical pathway system safety monitoring and rational drug use. Methods: Application OpenFTA software, the research based on Petri net fault tree analysis, fault tree for qualitative and quantitative analysis, drug safety management of the fault tree is obtained by Monte Carlo simulation of minimum cut sets. Results: Through the simulation calculation the probability of top event-drug safety incidents occur. Conclusion: Based on Petri net monitoring Clinical Medication Safety of fault tree method may help the qualitative and quantitative analysis the influence factors of adverse events, for the development of safety precautions, improving medication safety.
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