Personalised medicine: How does DNA testing play a role in the prescription of medication?

In this fascinating article, highly respected consultant psychiatrist Dr Maciej Danilewicz shares his expert insight on personalised medicine and innovations in our understanding of how medication affects each person individually. The revered specialist also details what pharmacogenomic testing entails and how it can help practitioners prescribe the most effective medications for each individual patient.

What is personalised medicine? How does DNA testing play a role in the prescription of medication?

To talk about personalised medicine, we need to first discuss an international study called the Human Genomic Project, which was started in the early 21st century and is still ongoing. Through this study, we have gained knowledge which had allowed us to map human DNA.

In 2011, as part of this project, researchers tested and mapped DNA of identical twins and discovered that their DNA is not identical. Although everyone was expecting that the twins’ DNA would be identical, this was not the case, and instead, scientists found that micro-mutations exist in each person’s DNA which differentiate it from any other person’s DNA.

From this discovery, we moved on to test these micro-mutations, known as single nucleotide polymorphisms. These micro-mutations do not impact the functioning of our body because nature allows some imperfections. However, they do impact how medication is able to bind to a receptor and work.

For medication to be able to work fully, it must fit the receptor perfectly, like a key in a keyhole. When a person has a micro-mutation, or single nucleotide polymorphism, in the part of DNA that actually codes how the receptor looks, this medication will not fit perfectly. Therefore, it will not to bind to it and will only partially work on the receptor. Since around 2018, we have been able to those small mutations in the DNA to see which medications the patient will likely respond to and those which they will likely not respond to.

From the patient’s perspective, the important part of personalised medicine is understanding how the medication works on our body or, in the field of psychiatry, on our brain. Unfortunately, personalised medicine cannot give one hundred per cent accuracy on what we should or shouldn’t prescribe. It can, however, give around eighty per cent of accuracy in prescribing, which in psychiatry is very important.

Personalised medicine testing is particularly useful in psychiatry as we do not currently have any other tests that we can use to assess how well a patient may respond to a given medication. In other areas of medicine, however, this is not the case. For instance, a patient can visit their doctor for a blood test and discover that they have low iron levels. After prescribing iron, patients can then be retested to ensure the iron levels are fine and the person is cured of their problem. Until we developed pharmacogenomic testing, there was not a single test in the field of psychiatry that we could use to establish whether certain medications would be effective or ineffective in a patient.

How is the information obtained in this testing used to tailor a patient’s type of medication?

The format of pharmacogenomic testing is quite simple and doesn't require any special knowledge. A mouth swab is taken, which the patient can do in the clinic or at home. The instructions on how to do this swap are easy and straightforward and the patient is asked not to eat, drink or smoke for a period of time before obtaining the DNA. Once taken, the sample is put into an envelope and posted to the company that provides the test.

There are a number of laboratories around the world which have start doing these types of tests or similar. The most accessible from the UK is actually a laboratory in the United States through a representative in the UK who is licensed to transport biological material. It takes around 10 days for the results to be obtained. One important factor in US law is that a doctor must be assigned to approve the test when it is taken by the patient and sent off for analysis. Pharmacogenomic tests are licensed by America’s Food and Drug Administration (FDA) as medical tests and therefore they require a requisition form from a doctor.

Once processed, the doctor receives the results from the laboratory and meets with the patient to discuss which types of medication are mostly likely to be effective for them. In terms of dosage, there is also quite an important part of the test which looks at liver enzymes. As the majority of medication is metabolised (broken down) by the liver, the test also gives us an indication of which type of medication will be metabolised in a normal way.

Some types of medication might not be broken down by the liver as fast as expected, so the patient will require lower doses. Other types of medication, however, will be metabolised by the liver quite quickly and therefore, low doses of this medication will most likely not be effective because it will be gone before it actually takes any effect on the brain.

Based on the information the test provides on these two factors - the receptors in the brain and information about the liver - we advise patients of the most likely medication that should be effective for them. Another thing to mention is that this pharmacogenomic test also looks at some potential side effects of medication. This is mostly the risk of psychotropic medication induced weight gain, which is quite important, because people don't want to uncontrollably gain weight on those medications. The test also gives us some indications about problems like skin reactions, amongst others, to certain medications.

What are the potential benefits and drawbacks of this approach?

In terms of the benefits of pharmacogenomic testing or personalised medicine, this approach allows us to advise the patient on the medication and dosage that is most likely to be effective for them. I think it's worth mentioning that one of the studies done in America, which was used to actually license the test with the Food and Drug administration, looked at the effectiveness of treatment of patients with a first episode of depression.

In the test, there were two groups of patients - those who had taken the pharmacogenomic test (group A) and a group of patients who had not undergone the test (group B). In group B, with no pharmacogenomic testing, the accuracy of prescribing was only at around forty per cent, meaning that from the very first contact with a psychiatrist, less than half were prescribed the right, effective medicine for them in their first episode of depression. Therefore, approximately sixty per cent needed to change their medication soon after being prescribed as it was not effective.

However, in group A, where pharmacogenomic testing was performed, the effectiveness of first time prescribing was eighty per cent. As such, the definite benefit of using this type of testing is a one hundred per cent increase in the accuracy of prescribing.

There are also some other benefits. As it is a DNA test, the person doesn't ever need to repeat it. Pharmacogenomic testing is a one-off and is valid throughout a person’s lifespan. It’s also a very simple test, using only a mouth swab, so it is painless and can be done from the comfort of your home.

In terms of drawbacks, there are some points to consider. This type of testing does not give one hundred per cent accuracy because our DNA is only responsible for how we are born and any developmental changes can also impact on prescribing or the effectiveness of the medication.

Additionally, these methods are so new that we are still learning. In my practice, I've been using pharmacogenomic testing since 2019, around six months from the time that it was first available in the UK. Even just in these few years, the results are changing because we are learning more about the impact of some medications and the test itself is becoming more and more accurate.

The final disadvantage is the price. The test costs over £700 and it's not available through the NHS. Therefore, for some patients, paying this amount of money can pose a problem.

If you think you could benefit from a form of personalised medicine and wish to schedule a consultation with Dr Danilewicz, you can do so by visiting his Top Doctors profile.