Do Genetics Affect Citalopram or Escitalopram?

Which Is Right for Your Patient: Citalopram or Escitalopram?

Citalopram and escitalopram are among the most widely prescribed antidepressants in the UK, often chosen for their effectiveness in treating depression and anxiety. While they share a chemical origin, subtle differences in their structure and metabolism can lead to very different outcomes—particularly when genetics come into play.

At AttoDiagnostics, we support the use of pharmacogenomic (PGx) testing to improve prescribing confidence and reduce the trial-and-error often involved in antidepressant treatment. Our PGx for Mental Health service helps clinicians tailor SSRI choices like citalopram and escitalopram based on a patient’s genetic profile.

Citalopram vs Escitalopram: What’s the Difference?

Citalopram is a racemic mixture, meaning it contains two mirror-image molecules: R-citalopram and S-citalopram. Only the S-form is pharmacologically active. Escitalopram is the pure S-enantiomer, making it more focused in action and approximately twice as potent. Despite this close relationship, their metabolism and clinical effects differ in meaningful ways—especially in relation to genetic variability.

How Genetics Influence Response to Citalopram and Escitalopram

CYP2C19 Gene

Both citalopram and escitalopram are primarily metabolised by the CYP2C19 enzyme. Variants in the CYP2C19 gene can significantly affect how much active drug builds up in the bloodstream.

• Poor metabolisers break down the drug slowly, resulting in higher blood levels and a greater risk of side effects, such as nausea, dizziness, or QT interval prolongation.

• Ultrarapid metabolisers process the drug too quickly, often leading to subtherapeutic levels and poor response.

Current guidance recommends dose adjustments or alternative therapies based on CYP2C19 status—particularly for citalopram, where the risk of QT prolongation is more closely linked to plasma concentration.

CYP3A4 and CYP2D6 Genes

While CYP2C19 is the dominant pathway, CYP3A4 (and to a lesser extent, CYP2D6) may also play a secondary role—especially in long-term use or in poor CYP2C19 metabolisers, where other enzymes may compensate. This secondary metabolism can vary, adding another layer of complexity when multiple medications are involved (e.g. in polypharmacy).

SLC6A4 Gene (5-HTTLPR Polymorphism)

Both citalopram and escitalopram target the serotonin transporter, encoded by the SLC6A4 gene. A well-known genetic variation called 5-HTTLPR influences how this transporter functions.

• Individuals with certain forms of this gene (e.g. the short allele) may have a blunted response to SSRIs and an increased risk of side effects.

• These patients might benefit from lower starting doses, closer monitoring, or consideration of alternative antidepressants.

What Does This Mean for Patients in the UK?

In the UK, pharmacogenomic testing for antidepressants and other psychiatric conditions is gaining traction—particularly for patients who have experienced side effects or poor response to first-line medications. By analysing genes like CYP2C19, CYP2D6, and SLC6A4, clinicians can make more informed decisions when prescribing SSRIs like citalopram or escitalopram. This type of testing is not yet standard practice, but it represents a move toward personalised mental health care—reducing the risk of trial-and-error prescribing and improving patient outcomes more quickly.

Are You Interested in PGx Testing for Antidepressants?

At AttoDiagnostics, we offer PGx reports that are:

• Clinically relevant

• Actionable in the UK context

• Easy to interpret alongside current NICE guidance

If you’d like to explore how pharmacogenomic testing could improve your mental health prescribing, please get in touch or use our quote request form to get started.

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