Ecitalopram

Pharmacogenomic (PGx) testing can help predict how a patient will respond to escitalopram, a widely prescribed SSRI for depression and anxiety. Genetic differences in drug metabolism—particularly involving CYP2C19—can influence both treatment efficacy and the likelihood of side effects. Understanding these variations supports more personalised and safer prescribing decisions.

Many of the pharmacological properties of citalopram apply to escitalopram. However, the two medications differ in important ways—especially in dosage and pharmacodynamic precision.

Citalopram is a racemic mixture, meaning it contains equal parts of two mirror-image molecules: R-citalopram and S-citalopram. Only the S-form (escitalopram) is therapeutically active. In fact, the R-form doesn’t just lack activity—it may actually inhibit the effectiveness of S-citalopram (31, 32). This explains why escitalopram is:

• Almost twice as potent as citalopram

• Faster acting, with some studies suggesting therapeutic effect from week 1, compared to week 6 for citalopram

• Potentially more effective in severe depression, especially where a robust response is needed

That said, in cases of mild-to-moderate depression or maintenance therapy, escitalopram has not consistently outperformed other antidepressants. It is not universally more effective—it’s more precise.

SSRIs Can Interact With Other Medicines and Supplements

Escitalopram, like all SSRIs, increases serotonin levels in the brain. When combined with certain supplements or medications, this can result in serotonin syndrome, a potentially serious condition. Patients should inform their GP or pharmacist if they are taking:

• Tryptophan

• St. John’s Wort

• Any other serotonergic agents

These combinations can increase the risk of excessive serotonin activity.

Increased Suicidal Thoughts in Early Treatment

As with all SSRIs, escitalopram may increase suicidal thoughts during the first four weeks of treatment (2, 10, 11). This risk is most pronounced in children, adolescents, and young adults. Patients and caregivers should be made aware of this possibility and know that it typically subsides as treatment continues.

Ecitalopram Side Effects

SSRIs like escitalopram are generally well tolerated, but some people may be more prone to adverse effects—especially those with certain genetic profiles. Pharmacogenomic (PGx) testing can help identify patients at higher risk of rare but serious side effects, such as:

• Serotonin syndrome

• Prolonged QT interval

• Hyponatraemia

These syndromes are complex and not exclusive to SSRIs, but their likelihood and severity may be influenced by genetic variation, drug interactions, and patient-specific risk factors.

Notably, escitalopram has been associated with a slightly higher rate of QT interval prolongation than citalopram (30), making it important to monitor cardiac risk—especially in older patients or those on multiple medications.

Serotonin Syndrome

Serotonin syndrome is a potentially life-threatening reaction caused by excess serotonin activity, often triggered by combining serotonergic agents or introducing a new one.

• In ~30% of cases, symptoms begin within 1 hour

• In ~60%, onset occurs within 6 hours

Common signs and symptoms:

• Mental status changes: Agitation, confusion, anxiety, hypomania, hypervigilance, seizures, coma

• Neuromuscular: Tremor, poor coordination, myoclonus (repetitive muscle twitches)

• Autonomic: Sweating, tachycardia, diarrhoea, fever, hyperthermia (>40°C)

You do not need all symptoms to be diagnosed. Serotonin syndrome can be mild—but it can also be fatal, and urgent medical attention is essential.

Prolonged QT Interval

Escitalopram has one of the strongest associations with QT interval prolongation among SSRIs—even more than citalopram (2, 3, 30). Prolonged QT can lead to arrhythmias, fainting, and, in rare cases, sudden cardiac death. Symptoms may include:

• Palpitations

• Light-headedness

• Fainting or near-fainting

• Weakness

• Seizures (in severe cases)

Risk factors (7):

• Female sex

• Older age

• Use of multiple QT-prolonging drugs

• Electrolyte imbalances (low potassium, magnesium, calcium)

• Use of diuretics

• Hepatic or renal dysfunction

• Bradycardia

• Inherited or silent long QT syndrome

• Heart conditions (e.g. heart failure, LVH, MI)

• Digitalis use

If these symptoms occur, patients should seek immediate medical attention.

Hyponatraemia

Hyponatraemia is a drop in sodium levels in the blood, occasionally seen with SSRI use—including escitalopram. The condition can range from mild to life-threatening. Symptoms vary based on severity and speed of onset:

• Severe: Vomiting, altered consciousness, coma, brain oedema

• Moderate: Disorientation, mood swings, drowsiness

• Mild: Behavioural changes, reduced focus, fatigue

Even mild cases require medical attention to prevent worsening.

Other Side Effects

In addition to rare but serious reactions, escitalopram can cause more common side effects that vary between individuals. These include:

• Anxiety

• Abnormal appetite

• Dry mouth

• Joint pain

• Chronic fatigue

• Impaired concentration

PGx testing can help explain why some patients experience these side effects more intensely, and guide decisions about switching or adjusting medication.

Understanding a patient’s CYP2C19 status can improve the safety and precision of escitalopram prescribing.

• Patients with reduced CYP2C19 activity are at increased risk of higher plasma concentrations, which may lead to side effects or QT prolongation.

• Ultra-rapid metabolisers, by contrast, may not reach adequate therapeutic levels, risking poor response.

Although formal dosing guidelines vary, PGx results can support a more targeted approach to titration and monitoring, helping reduce trial-and-error prescribing.

Related Medications:

Pharmacogenetic considerations involving CYP2C19 or CYP2D6 also apply to other antidepressants, including:

• Citalopram – closely related to escitalopram, also CYP2C19-sensitive

• Sertraline – metabolised by both CYP2C19 and CYP2D6

• Amitriptyline – a tricyclic antidepressant influenced by both CYP2C19 and CYP2D6

• Paroxetine – primarily metabolised by CYP2D6

PGx testing provides an opportunity to select the most appropriate SSRI based on each patient’s genetic profile, not just symptom presentation.