Abstract
Atypical antipsychotic medications are partly metabolised in the liver through CYP450 pathways. The rate of this metabolism is genetically determined such that one sees ultra-rapid, extensive, intermediate and poor metabolisers.
The metabolism rate is important since it plays a central role in determining the bio-availability of the drug. It is anticipated that the ultra-rapid metaboliser will have significantly lower blood levels from a particular dose when compared with extensive (normal) metabolisers. Intermediate and slow metabolisers will have higher blood levels.
There is evidence that both the effectiveness of the drug, the side effects experienced and the tolerability are all related to blood levels of drug.
The AmpliChip CYP450 Genotyping Test has been approved for testing CYP2D6 and 2C19 polymorphisms. These polymorphisms influence how an individual metabolises prescription medicines including antipsychotics such as risperidone is partly metabolised by CYP2D6 to 9-hydroxyrisperidone which has similar pharmacological activity to risperidone. Risperidone plus 9-hydroxyrisper-idone form the active antipsychotic fraction. In a clinical study with patients taking risperidone, CYP2D6 poor metaboliser status was found to be associated with adverse drug reactions and increased odds of discontinuing treatment due to these reactions
The hypothesis is that if clinicians have available the CYP450 status of the patient at the initial point of decision-making regarding risperidone dose and at each subsequent prescription review they will adopt differing dosing strategies in an attempt to achieve similar blood levels across the range of metabolisers. It is further hypothesised that this tailoring of dosage will be related to fewer side effects, enhanced tolerability, better adherence and improved outcomes.
This paper will present the outcomes of a study designed to test whether knowing CYP 450 metaboliser status was a useful clinical decision tool for psychiatrists in every day practice.