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Sunday, July 27, 2025

Escitalopram


Escitalopram is a widely prescribed antidepressant that belongs to the class of selective serotonin reuptake inhibitors (SSRIs). It is the S-enantiomer of citalopram, meaning it is the pharmacologically active component responsible for the antidepressant effects of racemic citalopram. Escitalopram is used in various psychiatric conditions due to its high selectivity for the serotonin transporter (SERT), and it is known for having a favorable tolerability and side-effect profile in comparison to older antidepressants.

Pharmacological Classification

  • Therapeutic class: Antidepressant

  • Pharmacologic class: Selective serotonin reuptake inhibitor (SSRI)

  • ATC code: N06AB10

  • Chemical name: S-(+)-citalopram

  • Brand names: Lexapro (U.S.), Cipralex (EU), Esertia, Nexito, among others

  • Legal status: Prescription-only (Rx)

Mechanism of Action

Escitalopram functions by selectively inhibiting the reuptake of serotonin (5-HT) in the central nervous system by binding to the serotonin transporter (SERT). This results in increased serotonin concentrations in the synaptic cleft, enhancing neurotransmission in serotonergic neurons, which plays a crucial role in mood regulation, anxiety control, and cognitive function.

Escitalopram has negligible affinity for other receptors (e.g., adrenergic, histaminergic, dopaminergic, muscarinic), making it one of the most selective SSRIs on the market. This selectivity contributes to its relatively low incidence of off-target side effects, such as anticholinergic or sedative effects.

Therapeutic Indications

Escitalopram is indicated for a wide range of psychiatric disorders, mainly involving mood and anxiety regulation.

Approved Uses (Adults)

  • Major Depressive Disorder (MDD)

  • Generalized Anxiety Disorder (GAD)

  • Social Anxiety Disorder (SAD)

  • Panic Disorder, with or without agoraphobia

  • Obsessive-Compulsive Disorder (OCD) (in some countries)

  • Premenstrual Dysphoric Disorder (PMDD) (off-label use in some regions)

Approved Uses (Pediatrics)

  • MDD in adolescents aged 12–17 years (approved in the U.S. and other countries)

  • Generalized Anxiety Disorder in adolescents (approved in some jurisdictions)

Dosing and Administration

Escitalopram is administered orally and is available in tablet form (5 mg, 10 mg, 20 mg) and oral solution (1 mg/mL).

Initial Dosing (Adults)

  • MDD and GAD: Start with 10 mg once daily

  • May be increased to 20 mg/day after a minimum of 1 week, based on response and tolerability

Panic Disorder

  • Initial dose: 5 mg/day for 1 week, then increase to 10 mg/day

  • Maximum: 20 mg/day

Elderly or Hepatic Impairment

  • Recommended maximum dose: 10 mg/day

  • Slower titration may be required

Adolescents

  • Initial: 10 mg/day

  • Titration and maintenance per clinical response

Escitalopram has a half-life of 27–32 hours, allowing once-daily dosing, and steady-state levels are reached within 1 week.

Contraindications

  • Concomitant use with monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuation

  • Hypersensitivity to escitalopram or citalopram

  • Congenital long QT syndrome (risk of QT prolongation)

  • Concomitant use with pimozide (due to QT prolongation)

Warnings and Precautions

Suicidality

  • Increased risk of suicidal thoughts and behavior, especially in children, adolescents, and young adults within the first few months of therapy

  • Monitor closely for mood changes, agitation, or suicidal ideation

Serotonin Syndrome

  • Risk increased when used with other serotonergic agents (e.g., triptans, tramadol, MAOIs)

  • Symptoms: agitation, hallucinations, tachycardia, hyperreflexia, clonus, fever

QT Prolongation

  • Escitalopram can cause dose-dependent QT interval prolongation

  • Use with caution in patients with electrolyte disturbances, heart disease, or concomitant QT-prolonging drugs

Hyponatremia

  • Especially in elderly patients and those on diuretics

  • Due to SIADH (syndrome of inappropriate antidiuretic hormone secretion)

Seizures

  • Use cautiously in individuals with a history of epilepsy

  • Discontinue if seizures occur

Bleeding Risk

  • Increased when combined with NSAIDs, aspirin, anticoagulants, or antiplatelets

Adverse Effects

Very Common (≥10%)

  • Headache

  • Nausea

  • Insomnia

  • Somnolence (drowsiness)

  • Increased sweating

Common (1–10%)

  • Fatigue

  • Dizziness

  • Dry mouth

  • Diarrhea or constipation

  • Weight changes (usually minimal)

  • Decreased libido or sexual dysfunction (delayed ejaculation, anorgasmia)

  • Appetite changes

  • Anxiety, restlessness

Less Common to Rare (<1%)

  • QT prolongation, palpitations

  • Mania or hypomania, especially in bipolar patients

  • Hyponatremia, seizures

  • Angle-closure glaucoma (rare)

  • Rash, pruritus, urticaria

  • Agitation, akathisia

Discontinuation Syndrome

  • Symptoms: irritability, nausea, dizziness, electric-shock sensations, insomnia

  • Gradual tapering is recommended when discontinuing

Drug Interactions

Pharmacodynamic Interactions

  • Other serotonergic agents: Risk of serotonin syndrome

    • e.g., MAOIs, SSRIs, SNRIs, tramadol, triptans, linezolid

  • NSAIDs/anticoagulants: Increased risk of bleeding

  • Alcohol: May potentiate sedation and impair psychomotor function

Pharmacokinetic Interactions

  • CYP2C19 inhibitors (e.g., omeprazole, fluconazole): May increase escitalopram plasma concentration

  • CYP3A4 and CYP2C19 inducers (e.g., carbamazepine, rifampin): May reduce efficacy

  • Lithium or tryptophan: Increased serotonergic effects

  • St. John's Wort: Risk of serotonin toxicity

Use in Special Populations

Pregnancy

  • Category C (U.S.) / B3 (Australia)

  • Associated with neonatal adaptation syndrome, including jitteriness, respiratory distress, feeding difficulties, and seizures

  • Potential association with persistent pulmonary hypertension of the newborn (PPHN)

  • Weigh maternal benefit against fetal risk

Lactation

  • Excreted into breast milk in small amounts

  • Use with caution; monitor infant for sedation, irritability, or feeding problems

Elderly

  • Lower starting doses recommended (e.g., 5–10 mg/day)

  • Monitor for hyponatremia and QT prolongation

Discontinuation

Gradual dose tapering over at least 1–2 weeks is recommended to minimize withdrawal symptoms. Abrupt discontinuation may lead to discontinuation syndrome, especially after long-term or high-dose use.

Clinical Trial Evidence and Efficacy

Escitalopram has been evaluated in numerous placebo-controlled and head-to-head trials, demonstrating efficacy in:

  • Reducing depression scores (HAM-D, MADRS) within 1–2 weeks of treatment

  • Prolonging time to relapse in long-term use

  • Improving anxiety scores in GAD, panic disorder, and social anxiety

Compared to citalopram and other SSRIs, escitalopram shows faster onset, better tolerability, and lower dropout rates in many studies.

Comparison with Other SSRIs and Antidepressants

Vs. Citalopram

  • Escitalopram is the active S-enantiomer, with higher binding affinity for SERT

  • Requires lower dose to achieve same or better efficacy

  • Fewer QT concerns at therapeutic doses compared to high-dose citalopram

Vs. Sertraline and Fluoxetine

  • Sertraline is more activating, often used in patients with fatigue

  • Fluoxetine has a long half-life (good for poor adherence but higher risk of interaction)

  • Escitalopram has less sexual dysfunction and fewer GI effects compared to sertraline

Vs. SNRIs (e.g., venlafaxine, duloxetine)

  • SNRIs have broader action (norepinephrine reuptake), may help with neuropathic pain

  • SSRIs, including escitalopram, are better tolerated and carry less hypertensive risk

Patient Counseling Points

  • Take once daily, preferably at the same time each day

  • May be taken with or without food

  • Initial effects may be noticeable after 1–2 weeks, but full effect takes 4–6 weeks

  • Do not stop abruptly — withdrawal symptoms may occur

  • Avoid alcohol and consult before taking OTC or herbal products

  • Inform physician of mood changes, suicidal ideation, or unusual behavior

  • Sexual side effects are common — discuss openly with provider

  • Pregnancy and breastfeeding risks should be discussed if applicable




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