Pharmacogenomics in psychiatry
For many patients, certain medications do not work as well as expected. For other patients the standard dose can cause toxic effects. For some of these patients, the reason may be genetic.
Pharmacogenomic testing has the potential to identify patients who are most at risk of a poor response to medication or adverse effects, and to tailor treatment accordingly. This is an area of medicine that is being increasingly recognised and investigated using clinical trials.
In psychiatry, it can be a challenge to predict the efficacy, side effects and optimal psychotropic dose for individual patients. At present, most prescribers use the approach ‘start low, go slow’. If patients are unresponsive or adverse effects occur, medication is changed.
This period of trial and error is time consuming and can be problematic for the patient. Pharmacogenomic testing has the potential to improve the clinical decision-making process.
About myDNA in psychiatry
Variations in certain genes have been found to influence drug exposure and drug effects. Drug exposure is how much drug is present at a site of action over time. Drug effects refers to the action of the drug on its target, which for a psychotropic is often a neurotransmitter receptor or transporter.
Currently myDNA testing concentrates on the genes that encode the metabolising enzymes, the CYP450 enzymes. These are found mainly in the liver, but also in the gut wall and other sites. These enzymes influence drug exposure.
In general, genetic variations predict the level of enzyme activity, which in turn results in increased or decreased plasma concentrations and drug exposure. Increased plasma concentrations, due to reduced enzyme activity, can lead to adverse effects. Reduced plasma concentrations, due to increased enzyme activity, can lead to poor therapeutic response.
For example, there is good evidence showing that patients who are CYP2D6 poor metabolisers have higher rates of adverse effects with risperidone than patients who are CYP2D6 extensive (normal) metabolisers (de Leon 2005).
Enzyme function can also be affected by factors other than genotype, including the effect of co-administered drugs, age and the presence of liver disease. These should be taken into account when considering a myDNA Medication test result. It is worth noting that when the enzyme function is genetically predicted to be severely reduced or absent, these additional factors are less able to affect function.
What does the myDNA Medication test cover?
Variations in eight genes are currently tested: CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, SLCO1B1 and VKORC1.
A large amount of published data in psychiatry pharmacogenomics relates to the effects of genetic variations in CYP2D6 and CYP2C19. These enzymes metabolise a number of important and commonly used psychotropic medications, especially antidepressants and antipsychotics.
For full list of medications commented on by myDNA, email us at email@example.com.
Clinical application and guidelines
The extent to which a psychiatrist can incorporate genetic test results into prescribing decisions varies according to the quality of supporting evidence.
For drug-gene interactions where the level of evidence is strong, peer-reviewed guidelines have been published. For other gene-drug interactions where the level of knowledge is still preliminary, the test information can still be taken into account when prescribing.
Ordering the myDNA Medication test
A myDNA Medication test can be ordered using the following methods:
- A blood test can be ordered in your clinic through Australian Clinical Labs (formerly Healthscope Pathology). The sample required is 4mLs of EDTA blood. This costs $169, although other pathology providers may add an additional charge for blood collection.
- The patient can be referred for a cheek swab, costing $149, to a pharmacy participating in the myDNA program. The sample is then sent to the lab for analysis and an interpretation report is sent back to the requesting doctor. A copy is also sent to the myDNA accredited pharmacist, who consults with the patient and will communicate with their doctor if the myDNA report suggests potential changes to current medications. Otherwise, the patient is advised to discuss the results with their doctor at their next appointment.