The drugs don’t work: how precision medicine can help treat patients

Up to two-thirds of patients with major depression fail to respond to their initial antidepressant, and less than 50% of patients achieve remission within 12 months of commencing therapy.

That’s a problem that genetic pathologists are trying to remedy through individualised medicine: looking at an individual’s genetic and metabolic makeup to work out the best course of treatment for an individual.

According to a report published in the March edition of the Australian Journal of General Practice, a person’s genetic makeup and metabolism impacts the way people respond to medication, which can result in insufficient dosage or adverse drug reactions in many cases.

The relationship between genes and how your body processes medication is called pharmacogenomics – a branch of genetic pathology that allows a person to be tested to determine the most effective medicine and the best dosage.

One of the paper’s authors, genetic pathologist, Professor Graeme Suthers, explains how pharmacogenomics could help improve the prescription of medicines.

‘Approximately 96% of the population has what are called “pharmacogenetic* variants” that can slow down or accelerate the breakdown of common medications in the body.

‘A pharmacogenomic variant can affect how a medication is absorbed from the gut, distributed in the body, broken down, and excreted by an individual.

’We recently examined data of about 30 medications from the Pharmaceutical Benefits Scheme and found that 1.7 million Australians take medications that are influenced by pharmacogenomic variants, and that 40% of them would be expected to have pharmacogenomic variants relevant for that medication.’

This genetic variation helps explain the difficulty experienced by some in finding the right medication for depression and other mental illnesses.

But thankfully, science has developed genetic tests that can help determine the right course of medication for a patient.

Patients can now have what’s called a pharmacogenomic test (PGX) that helps a clinician to understand an individual’s makeup and to prescribe the right drug at the right dose.

There are two genes primarily responsible for the metabolism of many antidepressants, and by understanding through a PGX test how these genes are working in individual patients, the treatment course can be individualised for optimal effect.

This idea of getting a genetic read of an individual to tailor medicine sounds like an approach from the future but has in fact been around for 50 years. But it is only now that pathologists know enough about combinations of drugs and genes that this type of testing is becoming “mainstream”.

‘Pharmacogenomics has taken hold in Europe and America, but in Australia at the moment we’re a little behind on education, regulation, rebates and national guidelines,’ said Professor Suthers.

‘Now is the time for clinicians, pathologists, educators, and regulators to work together to develop the guidelines and resources to ensure that Australian patients benefit from the responsible use of pharmacogenomics in daily practice.’

* pharmacogenetics usually refers to how variation in one single gene influences the response to a single drug. Pharmacogenomics is a broader term, which studies how all of the genes (the genome) can influence responses to drugs.