Personalised approaches to pharmacotherapy for schizophrenia

Abstract

SummaryThe traditional approach to selecting antipsychotic medication involves little more than trial and error. Recent advances in genetics and molecular science offer the hope of a ‘personalised medicine’ approach to antipsychotic development and prescribing in schizophrenia. Personalised medicine is the practice of tailoring medical treatment to the individual characteristics of each patient. In schizophrenia, this will involve the identification of more homogeneous subsets of patients through the application of genetics, epigenetics, proteomics and metabolomics, neuroimaging and other biomarkers, and the use of these findings to stratify patients according to their response to treatment. In this article, we focus on the emerging evidence in pharmacogenetics and biomarkers for assessing individual response and tolerability of antipsychotic medication in schizophrenia.

Treatment-resistant schizophrenia: current insights on the pharmacogenomics of antipsychotics

“…Table 4 summarizes significant findings from candidate gene studies of clozapine efficacy and side effects 32–37,92–94,96,100,106,108,109,117–136…”

<p>The CYP2C19*2 and CYP2C19*17 Polymorphisms Influence Responses to Clozapine for the Treatment of Schizophrenia</p>

“…Although pharmacotherapy can be used to treat this disorder, approximately one-third to one half of patients are unresponsive to current treatments, and are therefore deemed to exhibit treatment-refractoryschizophrenia (TRS). 1,2 Refractoriness is defined as the lack of satisfactory clinical response to treatments with at least two antipsychotic drugs, of the first or second generation, given at therapeutic doses and for at least six weeks during treatment. 3 When refractoriness occurs, CLZ is the drug of choice for treatment.…”

Objective and quantitative equilibriometric evaluation of individual locomotor behaviour in schizophrenia: Translational and clinical implications

“…31,36,46,49,50,[58][59][60] Our research data provide further evidence that the treatment decisions for the individual schizophrenic patients are more correct if they are guided by the objectively measured LMPs. 4,5 Such an objective and quantitative evaluation at a single-patient level is in line with the modern tendency for personalized 36,61,62 and precision 63,64 medicine in the psychiatric neuroscience research, aimed at replacing the traditional categorical diagnostic approach with a more dimensional one 64-68 that looks for "theranostic" 69 rather than for diagnostic biomarkers. 67,68 It is interesting to note that just in the last few years the motor dimension was proposed to be included in the translational psychiatric neuroscience research.…”

“…As mentioned before, every single schizophrenic patient might combine prototypical schizotaxic LMPs (indicating locomotor ataxia) with atypical nonschizotaxic ones (indicating either hypolocomotion or hyperlocomotion). Evaluating such subclinical combinations of qualitative and quantitative locomotor abnormalities could allow us to make more reliable predictions for more appropriate drug therapy and its more accurate dosage, which might lead to individualized or personalized treatment strategies . On the other hand, the diversity of possible locomotor combinations could explain why the individual reactions to one and the same antipsychotic treatment might vary from patient to patient and why these individual reactions are more predictable by objective evaluation of the patient's motor abnormalities .…”

“…12,14 itative and quantitative locomotor abnormalities could allow us to make more reliable predictions for more appropriate drug therapy and its more accurate dosage, 19,29,36,40,46,51 which might lead to individualized or personalized treatment strategies. [59][60][61][62][63][64] On the other hand, the diversity of possible locomotor combinations could explain why the individual reactions to one and the same antipsychotic treatment might vary from patient to patient and why these individual reactions are more predictable by objective evaluation of the patient's motor abnormalities. 46,[68][69][70][71][72] As we consider the schizotaxic LMPs as locomotor biomarkers for early detection of vulnerability to develop schizophrenia, such an approach links our findings with the classical neuroscience tradition of translational animal research in psychiatry.…”