Clinical Research Directory

PhaRmacOgenetics and Therapeutic Drug Monitoring In SchizophrEnia

Sponsor: Assistance Publique Hopitaux De Marseille

Summary

Schizophrenia is a severe chronic mental disorder with a long-term treatment. Most antipsychotic (AP) drugs are effective for only 30% to 60% of patients and for many drugs, treatment selection remains a "trial-and-error" process.The main result of treatment inefficiency is relapse, the recurrence of acute symptoms after a period of partial or complete remission. Pharmacogenetics (PG) is the study of genetic differences in drug met-abolic pathways which can affect individual responses to drugs, both in terms of therapeutic effect as well as adverse effects. PG testing could therefore identify patients at potentially high risk of relapse allowing the opportunity of an individualized prescription. In this study, PG was shown to improve the safety profile of AP treatments in patients presenting PM or UM CYP variants, by reducing associated side effects. Therapeutic Drug Monitoring (TDM) is the quantification and interpretation of drug concentration in blood to optimize pharmacotherapy . For drugs with established therapeutic reference ranges (TRR) or with a narrow therapeutic index, it makes sense to measure drug concentrations in blood for dose titration after initial prescription or after dose change. Non adherence is a recurrent problem in the management of schizophrenia, leading to reduced quality of life and increased risk of relapse. TDM is recognized as a direct reliable measure for drug adherence and can be an additional support after a therapy adjustment. Additionally, TDM can be useful to educate patients and make them more aware of their treatment. Finally, TDM is likely to ensure a better tolerance and fewer side effects for APs, while allowing a better efficacy. However, evidence on the clinical impact of this tool in schizophrenic population is lacking and randomized clinical trials are needed to confirm it. Finally, relapses occur frequently in schizophrenia and the cost for a relapsing schizophrenic patient is estimate over 4 times higher than for a non-relapsing patient, highlighting the importance of cost-effective care strategies. When separately used PG testing or TDM alone, might not be sufficient to ensure the clinical utility and cost-effectiveness of these tests. We hypothesize that individualized medicine including the association of PG testing with TDM (PG/TDM intervention), on the most commonly prescribed AP drugs, can reduce relapse rate at one year while being cost-effective.

Official title: How Personalized Medicine Based on Pharmacogenetics and Therapeutic Drug Monitoring Can Reduce Relapse Rate in Patients WITH schizophreniA: An Analytical, Experimental, Prospective, Comparative, Adaptive Randomized, Open-label, Multicenter Clinical Trial

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