Towards personalized pharmacology: Antipsychotics and schizophrenia

Since the discovery of the first antipsychotic in 1952, many antipsychotic drugs have been developed, each with different pharmacokinetic and pharmacodynamic properties. The pharmacological heterogeneity of antipsychotic drugs should allow a personalized drug prescription adapted to the different clinical picture of schizophrenia. Schizophrenia is a chronic disease, during which 3 stages of pharmacological intervention can be identified: the first episode psychotic (FEP), the phase of therapeutic stabilization that can progress to situations of resistance, and the question of long-term prescription. During FEP, the choice of the first antipsychotic treatment seems to be underpinned by its safety profile in relation to the patient for whom it is prescribed, according to the adage start low and go-slow. The therapeutic stabilization phase is based on treatment optimization through a rigorous evaluation of the benefits-harm balance, with the use of tools such as personalized therapeutic drug monitoring and pharmacogenetics. Generally speaking, while some antipsychotic drugs seem to present a more favorable efficacy profile in certain situations, the differences are small, whereas the differences in safety are more important and should be considered in the first line. Individual factors such as the presence of co-morbidities, as well as previously experienced treatments must also be taken into account. Finally, the question of maintaining the prescription of antipsychotic drugs over the long term arises in view of the iatrogenic risk with controversial current data. Overall, the personalized prescription of antipsychotic drugs in schizophrenia remains limited by a lack of data in the literature, justifying the development of clinical studies in this field. But at present, the dogma remains that of primum non nocere.