Part of the answer lies in our genes
There are many factors that influence our response to medication, including our size, foods we have recently eaten that affect absorption and other medications we are taking. Our genes can also have a big effect on whether a medication works for us, and how susceptible we are to side effects.
In many cases, differences in responses to medication can be due to faster or slower metabolism of a medication, so many studies involve searching for genetic variants that are linked to metabolism of a drug, a field of research called pharmacogenomics.
Ancestry plays a part
The number of genetic variants you have depends on your ancestry.
In 2021, the makers of the blood thinner Plavix were taken to court by the State of Hawaii and ordered to pay more than US$834 million to the state for failing to disclose that the drug could have a diminished or no effect in a large number of individuals of Pacific Island ancestry.
IMB’s Dr Sonia Shah explains that the genetic variant that makes the drug ineffective is only present in around 2.5 per cent of the European-ancestry population but occurs in about 45 per cent of Pacific Islanders and around 60 per cent of South Asians.
“However, clinical trials of this drug were conducted mostly on people of European ancestry.”
Diversity in research participants
“This is an important reminder of why diversity in research participants matters, especially when drugs are being developed for a global market,” Dr Shah says.
The ability to combine pharmacology – the science of drugs – with genomics is another tool in the quest to develop effective, safe medications that can be prescribed based on a person’s genetic makeup.
Which antidepressants work best?
Dr Shah is investigating how to better pinpoint which antidepressants will work for which patient.
“We don’t fully understand how different antidepressants work, and we’re also still learning about the biological changes in the body that may lead to depression. This means that currrently the only way to identify which treatment will work best is through trial and error.”
“Some people may have to try three or four types of antidepressants before they find one that works for them, and this process may take many months.”
Prediction instead of trial and error
“We’re hoping to speed up that process by growing up cells from these patients in the lab to try to predict the medication to which they are most likely to respond.
“Our hypothesis is that if we expose cells to an antidepressant in the lab, there will be differences in what genes get switched on or off depending on whether those cells come from someone who is known to respond to the antidepressant, or from someone who doesn’t respond.
“These differences create a gene expression ‘signature’ for antidepressant response that differs between responders and non-responders, and could allow us to develop a simple blood test to predict the best individual treatment relatively quickly.”
