Escitalopram

Selective serotonin reuptake inhibitors (SSRIs)

ATC code: N06AB10 (Escitalopram)

Mechanism of action

S-enantiomer of citalopram. The most selective SSRI – blocks the serotonin transporter with minimal effect on norepinephrine, dopamine, and other receptors. Two binding sites: primary (inhibits reuptake) and allosteric (stabilizes binding to the primary site). This provides more complete and rapid transporter blockade compared to racemic citalopram.

Indications

Generalized anxiety disorder

First line

Escitalopram is approved for generalized anxiety disorder. NICE and APA recommend SSRIs as first-line therapy for GAD. Start at 10 mg, may increase to 20 mg. In anxious patients, consider starting at 5 mg for the first week to minimize paradoxical anxiety worsening at treatment initiation. Response develops over 4-8 weeks.

Major depressive disorder

First line

Escitalopram is a first-line antidepressant per APA 2023 guidelines. Start at 10 mg once daily, increase to 20 mg after 3-4 weeks if needed. Maximum dose 20 mg daily. The Cipriani meta-analysis (2018, Lancet) ranked escitalopram among the top antidepressants for the balance of efficacy and tolerability out of 21 agents. Assess response at 4-6 weeks.

Social anxiety disorder

First line

Escitalopram is effective for social anxiety disorder. SSRIs are first-choice therapy per NICE and APA recommendations. Dosage is the same as for depression – 10-20 mg daily. Treatment is long-term – continue for at least 12 months after remission. Early discontinuation frequently leads to relapse.

Practical notes

Timing and administration

Take once daily in the morning or evening, with or without food. If it causes drowsiness, take in the evening. If insomnia, take in the morning. Do not stop abruptly – taper over 2-4 weeks. Abrupt SSRI discontinuation causes withdrawal syndrome: dizziness, paresthesias ("brain zaps"), irritability, nausea. With escitalopram this syndrome is milder than with paroxetine or venlafaxine, but still occurs.

Special situations

Maximum dose is strictly 20 mg daily due to dose-dependent QT prolongation. In patients over 65, maximum dose is 10 mg. Do not combine with other QT-prolonging drugs. ECG before starting therapy is recommended for patients with cardiovascular disease. Risk of serotonin syndrome when combined with tramadol, triptans, MAO inhibitors, lithium. Discontinue MAO inhibitors at least 14 days before starting escitalopram.

Safety

Contraindications

Concurrent use with MAO inhibitors (and within 14 days of their discontinuation)
QT prolongation or congenital long QT syndrome
Concurrent use with pimozide or other drugs that significantly prolong QT
Hypersensitivity to escitalopram or citalopram

Serious adverse effects

QT prolongation (dose-dependent, hence the 20 mg maximum)
Serotonin syndrome (when combined with serotonergic agents)
Hyponatremia – SIADH (more common in elderly, with concurrent diuretics)
Increased suicidal ideation in adolescents and young adults in the first weeks of treatment (FDA black box warning)

Common adverse effects

Nausea (especially in the first 1-2 weeks, then resolves)
Headache
Insomnia or somnolence
Sexual dysfunction (decreased libido, anorgasmia, delayed ejaculation)
Dry mouth
Sweating

PregnancyFDA C

FDA category C. SSRIs in the third trimester may cause neonatal respiratory distress, jitteriness, and irritability (neonatal adaptation syndrome). First-trimester use does not increase the overall risk of congenital malformations. The decision to continue therapy is individualized, weighing the risk of depression relapse for the mother against potential fetal exposure.

Breastfeeding

Excreted in breast milk. Relative infant dose is low. Escitalopram and sertraline are preferred SSRIs during breastfeeding per LactMed.