Antipsychotics metabolism

SGAs atypical antipsychotics Metabolism Inducers Inhibitors... 

Most robust pharmacogenetic findings for antipsychotic metabolism and response... 

These methodological differences account, at least in part, for the lack of replication observed across pharmacogenetic studies of antipsychotic response. Despite the challenges of conducting genetic studies in this area, a number of variants have shown consistent association with antipsychotic metabolism and response (Table 3). 

TABLE 34-9. Metabolism and Drug Interactions with Antipsychotics... 

Antipsychotic Major CYP450 Metabolic Enzyme Other CYP450 Metabolic Pathways Increase Antipsychotic Concentrations Decrease Antipsychotic Concentrations... 

Drug Interactions Carbamazepine induces the hepatic metabolism of many drugs, including other antiepileptic drugs, antipsychotics, some antidepressants, oral contraceptives, and... 

One approach to formulating potential differences in ethnic response is to examine the metabolic pathways of the common antipsychotics and determine whether the known ethnic variations in metabolizing enzymes or other effects on absorption, distribution, and excretion can be applied a priori to predict potential clinical effects. In this section we will consider some of the commonly prescribed SGAs, and only briefly touch on the FGAs. 

Table 4.2 Principal enzymes involved in metabolism of second-generation antipsychotics...

Quetiapine is predominantly metabolized by CYP3A4. Environmental rather than genetic differences are most likely to explain unusual differences in the serum concentration to dose ratio for this antipsychotic (de Leon etal, 2005b). 

As can be seen in Table 4.2, many agents commonly co-prescribed with antipsychotics may act as inducers and inhibitors. That these agents are also prone to ethnically determined variations in their own metabolism, suggests that providing the optimal dose of antipsychotics in various ethnic groups may become complex where psychotropic polypharmacy is common. 

Meyer, J. M., Nasrallah, H. A., McEvoy, J. P., Goff, D. C. et al. (2005). The clinical antipsychotic trials of intervention effectiveness trial clinical comparison of subgroups with and without metabolic syndrome. Schizophr. Res., 80, 9-18. 

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