The Role of Genetics in Citalopram and Sertraline Treatment

Do Genetics Affect Sertraline or Citalopram?

Citalopram and Sertraline are two of the most commonly prescribed antidepressants in the UK, often used to treat conditions like depression and anxiety. While these medications are effective for many people, their success can vary widely from person to person. A growing body of research suggests that genetics may play a significant role in determining how well these medications work and whether patients experience side effects. AttoDiagnostics are proud to support this research through our PGx for Mental Health service.

An Overview of Citalopram and Sertraline

Citalopram and Sertraline are both selective serotonin reuptake inhibitors (SSRIs), a class of drugs that work by increasing the levels of serotonin in the brain. Serotonin is a neurotransmitter that plays a key role in mood regulation. By preventing the reabsorption (reuptake) of serotonin into neurons, SSRIs help increase the availability of serotonin in the brain, which can alleviate symptoms of depression and anxiety.

While both drugs are generally well-tolerated, some patients experience side effects such as nausea, insomnia, sexual dysfunction, or increased anxiety. Additionally, the time it takes for the medication to become effective and the optimal dosage can vary significantly between individuals.

How Genetics Influence Response to Citalopram and Sertraline

Genetics can affect how a patient’s body metabolises these medications and how the brain responds to them. Several genes have been identified that influence the effectiveness and side effect profile of SSRIs like Citalopram and Sertraline.

CYP2C19 Gene:

The CYP2C19 gene encodes an enzyme that is crucial in the metabolism of Citalopram. Variations in this gene can lead to differences in how quickly or slowly Citalopram is broken down in the body. Individuals with certain variants of the CYP2C19 gene may metabolise the drug too quickly, resulting in lower-than-expected drug levels and reduced efficacy. Conversely, those with other variants may metabolise the drug more slowly, leading to higher drug levels and an increased risk of side effects.

• Ultrarapid Metabolisers: These individuals may break down Citalopram too quickly, potentially leading to inadequate response. Higher doses may be required to achieve therapeutic effects, but this should be done cautiously and under medical supervision.

• Poor Metabolisers: These individuals may metabolise the drug more slowly, which can increase the risk of side effects. Lower doses or alternative medications may be recommended for these patients.

Sertraline is also partially metabolised by the CYP2C19 enzyme, but it is less reliant on this pathway than Citalopram. This means that while CYP2C19 variations can influence Sertraline metabolism, the impact is generally less pronounced compared to Citalopram.

CYP2D6 Gene:

Another important gene in the metabolism of SSRIs, including Sertraline, is CYP2D6. This gene also encodes an enzyme that metabolises various drugs, and its activity varies significantly among individuals. Like CYP2C19, variations in CYP2D6 can classify individuals as ultrarapid metabolisers, normal metabolisers, or poor metabolisers.

For Sertraline, poor metabolisers may experience higher drug levels, increasing the likelihood of side effects such as nausea or fatigue. Ultrarapid metabolisers, on the other hand, may not achieve adequate drug levels, potentially leading to a lack of therapeutic effect.

SLC6A4 Gene:

The SLC6A4 gene encodes the serotonin transporter, which is the target of SSRIs like Citalopram and Sertraline. A well-known polymorphism in this gene, known as the 5-HTTLPR, affects the expression of the serotonin transporter and, consequently, the efficacy of SSRIs.

• Carriers of mutation in this gene may have a reduced response to SSRIs and may be more likely to experience side effects. Some studies suggest that these individuals might benefit from starting with a lower dose or choosing an alternative antidepressant.

What Does This Mean for Patients in the UK?

In the UK, pharmacogenomic testing that looks at genes like CYP2C19, CYP2D6, and SLC6A4 is becoming increasingly available and may help guide the choice and dosage of antidepressants like Citalopram and Sertraline. While this type of testing is not yet standard practice in all cases, it offers a promising avenue for personalising treatment plans and avoiding the trial-and-error approach that many patients currently experience.

If you’re considering genetic testing or want to learn more about how PGx testing could improve your practice, please get in touch using our get a quote form.