Senior consultant psychiatrist Dr Subash Kumar remembers the time he treated his patient Angela (not her real name) for severe depression after she lost her husband to cancer.

Feeling depressed and lethargic, she said: “It’s so difficult to get out of bed.”

Dr Subash decided on a combination treatment of antidepressant medication and therapy.

The antidepressant drug would help alleviate her mood in order for the therapy sessions to work on her negative thoughts.

Over the next three to four months, Angela still felt tired all the time and was struggling to keep her job.

She lost her interest to socialise and fell out of touch with her friends.

“The antidepressant medication was just not working,” said Dr Subash.

He eventually hit on the right combination of drugs for Angela after some trial and error.

Today, she has regained her energy and is able to cope with the pressures of work and life.

She is one of his luckier patients. Other patients have taken as long as six months before an effective drug could be found for them.

Trial and error

Determining the most effective drugs for any patient is a complex process, which currently involves trial and error.

A more accurate drug prescription could potentially save patients weeks, sometimes months, of adjustment, and alleviate the distress and symptoms of their illness faster, whether for mental or physical illness.

“You prescribe a medication that is supposed to work. But the patient comes back the next month because he doesn’t feel better. You then either raise or lower the dose,” explained Dr Subash.

“He comes back again and says it’s still not working. You change the drug to another one.

“Sometimes, you are just lucky if you prescribe the most effective one straight away.”

Now, he can potentially shorten the process greatly, thanks to a new drug-gene, or pharmacogenomics, test developed by a local genomics company.

According to the company, this first-of-its-kind test in Malaysia helps to support doctors’ ability to prescribe the right drug at the right dose according to their patient’s genetic profile.

Pharmacogenomics involves profiling the genes that are responsible for how drugs are metabolised, and is an important aspect of the personalised and precision medicine seen as the future of drug therapy.

This drug-gene test gives Malaysian doctors the opportunity to prescribe according to how specific medications react with their patients’ bodies.

“There’s no ‘one size fits all’ drug. This common assumption leads to patients wondering why their medications aren’t working for them, and many giving up on them altogether,” said the company’s chief operating officer Sasha Nordin.

“There are drugs that work well for a majority of patients, but just do not have the expected effect for others.”

Mutations affect metabolism

Genetic mutations can affect how biochemical pathways work when metabolising drugs, causing a patient’s body to retain or eliminate a drug at an unexpected rate.

Metabolised too slowly, a normal dose would result in abnormally high drug levels in the blood, which could be toxic.

Metabolised too quickly, a drug would not reach the necessary therapeutic level.

“Both outcomes are known as adverse drug reactions (ADRs), that is, harm caused by a drug taken at normally-prescribed doses and during normal use,” said Sasha.

“In drug development, ‘normal’ usually refers to what works for most people, or on average.

“But our DNA makes us different and makes our metabolism different.”

ADRs lead to poorer patient outcomes, increased medical costs, and also, increased medical liability, not to mention additional stress when patients do not feel that the drug prescribed is doing its job.

According to American and Canadian studies, ADRs are a leading cause of death.

Some ADRs are immediate and visible, but others cannot be clearly or quickly spotted, for example, in elderly patients or young children who may find it hard to describe how they fee.

It could also be due to the patient’s illness. With depression, for example, a doctor cannot test blood or urine to determine how well the treatment is working, said Dr Subash.

In the realm of mental health, this issue is critically important.

“It’s not like treating dengue fever or high blood pressure.

“I have to rely on my observations and what my patients tell me they are feeling or experiencing,” he added.

Doctors usually prescribe the best drug indicated, at a suitable dose and frequency based on the patient’s age, weight and observable conditions, and then monitor for effectiveness, toxicity and side effects.

The drug-gene test can identify from a blood sample a range of genetic mutations that influence how certain drugs work and help doctors minimise the risk of ADRs.

“Mutations on the CY2D6 gene adversely affect your body’s ability to metabolise commonly prescribed anti-depressants, such as fluoxetine, clomipramine and paroxetine.

“Knowing this, your doctor can prescribe drugs with lower or no genetic risk of ADRs,” said Sasha.

Beyond mental health, this pharmacogenomics test can also assist with drugs used in areas such as cardiology (e.g. statins and beta blockers) and pain management (e.g. NSAIDs), among others.

Getting the right drug at the right dose at the right time goes a long way to reducing the distress and frustration caused by illness, not just for the sufferers, but for their carers and family as well.

“This is objective data that can help mental health doctors prescribe based on evidence, and rely less on subjective information,” said Dr Subash.

This article is courtesy of Malaysian Genomics Resources Centre Bhd.