Why do people react differently to the same medication?

What is the relationship between genetics and the response to medication?

After you take a medicine, your body will need to break it down and get it to the area of your body where it’s needed. The variation in our genetic code can affect parts of this process, which can cause differences in how we break down and respond to medicines. This is because DNA codes for proteins.

Proteins are molecules that carry out important jobs in our bodies, such as breaking down drugs, taking up drugs into cells, or reading messages from other proteins at the surface of cells. Differences in our genetic makeup can cause variations in how proteins are made, which may affect how they behave[2].

Example 1 – Sam and Emma break down a medicine at different rates

Most medicines are broken down or ‘metabolized’ by enzymes in the liver. Enzymes are proteins that break down or build up substances in our bodies. One of these enzymes is called CYP2D6, and genetic variants in the gene that codes for this enzyme can cause it to break down medicines at different rates[3].   

Sam was given a standard dose of an antidepressant to treat his severe depression. Days after starting the treatment, he felt dizzy, tired, and confused. After some medical tests, it was found that Sam had double the recommended levels of the medicine in his blood. The drug dose was reduced, and Sam had no further side effects. Sam is classified as a poor metabolizer, as his ability to break down this medicine is slower than average, and he requires a lower dose to prevent adverse drug reactions and to benefit from the treatment[3].  Emma was given a standard dose of an antidepressant, and her blood was tested to check the drug levels. The medicine in Emma’s blood was much lower than the recommended level needed to benefit from the medicine, so her dose was increased. Over time, her dose was increased to 4–6 times more than the starting dose, which eventually provided Emma with the recommended levels in her blood. Emma is classified as an ultra metabolizer of the drug, as she needs much higher levels than average to benefit from the treatment[3].

Example 2 – Sam and Emma experience a different sensitivity to a medicine

Some medications work by targeting a protein found on the surface of cells, called a receptor. Small differences in our genetic makeup may change how these receptors behave when they are in contact with a drug. This can influence how well a medicine will work and whether any side effects are experienced[4,5]. 

Genetic variants in the gene that creates the HTR2A receptor also called the serotonin receptor 2A, can influence how effective certain medications are for treating mood and mental disorders such as depression and bipolar disorder[5].

Sam was given a standard dose of a medicine to treat a mood disorder. Due to a genetic variant in the HTR2A gene, he had a higher chance of responding well to the medicine[5]. However, his risk for side effects was also higher. This means that Sam should be monitored more closely for severe side effects by his healthcare provider[4]. 

Emma does not have this genetic variant in her HTR2A gene, and therefore has a lower chance of responding to the medicine[5]. This means that Emma should be monitored closely as the drug may not be effective enough to treat her disorder. It may be the case that Emma has a better response with a different drug instead.